Methods of identifying markers of enteropathies

Abstract

New and useful computer-implemented methods; methods of identifying markers associated with enteropathies; methods of determining the level of severity of an enteropathy; and determining a treatment for an enteropathy; are disclosed. In addition, the present disclosure provides methods of identifying a biological response to one or more treatments for an enteropathy, and whether a given treatment to an enteropathy results in a therapeutic or adverse effect, as determined in a spatiotemporal manner throughout the entirety of the small bowel, or a region of interest therein.

Description

Methods of Identifying Markers of EnteropathiesCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of, and priority to, United States Provisional Application Serial No. 63 / 641,565, filed on May 02, 2024, the contents of which are herein incorporated by reference in their entirety.TECHNICAL FIELD

[0002] New and useful methods of identifying markers associated with enteropathies; methods of determining the level of severity of an enteropathy; identifying a biological response to one or more treatments for an enteropathy; and determining a treatment for an enteropathy; are described and claimed.BACKGROUND

[0003] Enteropathies affecting the small bowel can produce a number of debilitating symptoms. One of the most common enteropathies in western countries is celiac disease (CeD): an immune-mediated disease characterized by abnormal T cell responses to gluten. Celiac disease (CeD), has a global prevalence between 0.5% and 1.0% depending on region and research methodology, is a common, chronic, immune-mediated disorder with gastrointestinal and non-gastrointestinal manifestations. See Rubio-Tapia, et al. The prevalence of celiac disease in the United States. Am J Gastroenterol. 2012;107(10):1538- 1544; quiz 1537, 1545; Lionetti et al. Celiac disease from a global perspective. Best practice & research Clinical gastroenterology. 2015;29(3):365-379; Leonard et al. Celiac disease and nonceliac gluten sensitivity: a review. JAMA. 2017;318(7):647-656; and Kelly et al.Advances in diagnosis and management of celiac disease. Gastroenterology. 2015;148(6): 1175-1186.

[0004] CeD is an immune reaction to dietary gluten protein (present in wheat, barley, rye and oat cereals) that affects the small intestine in genetically susceptible individuals. See Rubio-Tapia et al. The prevalence of celiac disease in the United States. Am J Gastroenterol. 2012;107(10): 1538-1544; quiz 1537, 1545. In all individuals, gliadin undergoes limited digestion by gastric, pancreatic, and intestinal brush border proteases in the uppergastrointestinal tract. These incompletely digested peptides enter the small intestine and, in susceptible individuals, can trigger an immune response.

[0005] One hallmark for diagnosis of CeD is the detection of an injury response induced by dietary consumption of gluten, wherein the response is detected by duodenal biopsy. See Kelly et al. Advances in diagnosis and management of celiac disease. Gastroenterology. 2015 ; 148(6): 1175-1186. Upper gastrointestinal endoscopy (EGD) and duodenal biopsy are employed to evaluate the small intestine for mucosal injury, which, along with symptoms, aid in assessing therapy response. Id.

[0006] The only recommended management option and best supportive care is a lifelong gluten-free diet (GFD). A strict GFD is effective in most patients, but it must be continued throughout the patient’s lifetime and adherence to it is difficult. Approximately 20% celiac patients on a gluten-free diet still experience disease symptoms due to accidental gluten ingestion. Recent studies have documented frequent gluten exposures of -500 mg in patients attempting to follow a strict GFD (Moreno AJG 2017, Syage 2018).

[0007] And, for many patients, symptoms and intestinal damage can be controlled by a gluten-free diet, but for some this approach is not enough and celiac disease progresses with serious medical consequences. Multiple therapies are now under development, increasing the need for biomarkers to allow identification of specific patient populations and to monitor therapeutic activity and durability.

[0008] Accordingly, there is a need to provide effective pharmaceutical interventions to mitigate the ill effects of enteropathies such as celiac disease in patients. The opportunity is to not only develop specific drug agents, but to development biomarker technology to facilitate the ongoing improvement of these agents as well as meet other goals pertinent to the overall experience of patients affected by this disease.SUMMARY

[0009] The present disclosure describes a computer-implemented method comprising: receiving an indication of: a first selection corresponding to an image that represents a portion of an internal cavity of an organ associated with a subject; or a second selection corresponding to a coordinate on a curve of a plot representing a quantitative metric that characterizes a region of the internal cavity of the organ associated with the subject; in response to the received indication, when the received indication corresponds to the first selection, determining a respective coordinate on the curve of the plot representing the quantitative metric that characterizes the region of the internal cavity of the organ, whereinthe respective coordinate indicates a position in the internal cavity where the image was captured, and a value for the quantitative metric at the position where the image was captured; when the received indication corresponds to the second selection, determining a respective image captured to represent the portion of the internal cavity of the organ associated with the subject, wherein the respective image was captured at a respective position corresponding to the coordinate indicated by the second selection; and displaying, at a graphical user interface: the coordinate or the respective coordinate in a first viewing window of the graphical user interface; and the image or the respective image in a second viewing window of the graphical user interface.

[0010] In addition, the present disclosure provides a computer-implemented method comprising: receiving medical imaging data characterizing a set of regions of the small bowel of a subject; processing the medical imaging data to generate a graphical representation that indicates an extent of enteropathy for the subject throughout the set of regions of the small bowel; and displaying, at a graphical user interface, the graphical representation simultaneously with corresponding medical imaging data such that: the graphical representation and the corresponding medical imaging data are observable by a user of the graphical user interface at the same time; and an element of the graphical representation is visually associated with a portion of the medical imaging data that generated the element.

[0011] In addition, the present disclosure provides a computer-implemented method comprising: receiving, at data processing hardware, a plurality of images capturing an extent of an internal cavity of an organ for a subject; for each image, determining, by the data processing hardware, a severity score that characterizes a degree of enteropathy for tissue within the internal cavity of the organ represented in the respective image; generating, by the data processing hardware, a graphical curve representing an intensity of injury for the tissue of the organ, wherein the graphical curve includes a set of points for the subject, wherein each point corresponds to the respective image and includes a coordinate pair identifying a position within the organ where the respective image was captured and the corresponding severity score for the respective image; classifying, by the data processing hardware, the graphical curve as a phenotype of enteropathy, and determining, by the data processing hardware, that the classified phenotype matches a stored phenotype of enteropathy.

[0012] In addition, the present disclosure provides a computer-implemented method comprising: receiving an indication of a selection corresponding to a coordinate on a curve of a plot representing a quantitative metric that characterizes a region of an internal cavity of an organ associated with a subject, wherein the coordinate includes a first number indicating aposition in the internal cavity, and wherein the coordinate further includes a second number indicating a value for the quantitative metric indicated by the first number; in response to the received indication: determining an image captured to represent a portion of the internal cavity of the organ associated with the subject, wherein the image corresponds to the position indicated by the first number; and displaying, at a graphical user interface: the coordinate comprising the first number and the second number on the curve of the plot in a first viewing window of the graphical user interface; and the determined image indicated by the selection in a second viewing window of the graphical user interface.

[0013] In addition, the present disclosure provides a method of identifying a marker of an enteropathy, or lack thereof, in a subject, the method comprising: (1) assessing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury; and (3) generating a marker; wherein the marker is indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0014] In addition, the present disclosure provides a method of identifying a marker of an enteropathy in a subject, the method comprising: receiving data corresponding to one or more indicators of small bowel injury in the subject; processing the one or more indicators of small bowel injury; and generating a representation of the one or more indicators of the small bowel injury.

[0015] In addition, the present disclosure provides a method of identifying a data- driven marker in the small bowel of a subject, the method comprising: receiving data corresponding to one or more indicators of small bowel injury in the subject; processing the one or more indicators of small bowel injury; generating a behavioral prediction to address the one or more indicators of small bowel injury; and communicating the behavioral prediction.

[0016] In addition, the present disclosure provides a method of identifying a marker of an enteropathy in a subject, the method comprising: receiving medical data characterizing a set of regions of the small bowel of the subject; and for the received endoscopy data, generating, by data processing hardware, a representation of the one or more indicators of the small bowel injury; wherein the representation graphically represents the set of regions characterized by the medical data.

[0017] In addition, the present disclosure provides a method of identifying a marker of an enteropathy in a subject, the method comprising: receiving medical imaging data characterizing a set of regions of the small bowel of the subject, wherein the medical imaging data comprises a set of imaging frames; for each frame of the set of imaging frames, determining a score indicative of the injury state of the small bowel captured by the respective imaging frame; and generating a graphical representation for the set of regions of the small bowel characterized by the medical imaging data based on the score of each frame of the set of imaging frames.

[0018] In addition, the present disclosure provides a method of identifying a marker of an enteropathy, or lack thereof, in a subject, the method comprising: (1) assessing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury; and (3) generating a summary score of the injury score.

[0019] In addition, the present disclosure provides a method of identifying a marker of an enteropathy, or lack thereof, in a subject, the method comprising: (1) assessing villous atrophy in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury; wherein the injury score comprises a level of injury determined via a visual assessment of one or more frames of a video; wherein the level of injury corresponds to an ordinal scale ranging from 0-3; wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy; (3) generating a summary score of the injury score by determining: (a) a curve fit to the injury score for the entirety of the small bowel of the subject, and using equally spaced points therein; and (b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; wherein one or more markers of an enteropathy, or lack thereof, are identified by assigning the summary score generated in Step (3) to: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or any combination thereof.

[0020] In addition, the present disclosure provides a method of recommending a treatment for an enteropathy in a subject in need thereof, the method comprising: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury; (3) generating a summary score based on the injury score; (4) identifying a marker of anenteropathy, or lack thereof, based on the summary score; and (5) recommending a treatment for an enteropathy based on the marker identified in Step (4).

[0021] In addition, the present disclosure provides a method of identifying a marker of an enteropathy, or lack thereof, in the small bowel of a subject, the method comprising: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury; (3) generating a summary score based on the injury score; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof.

[0022] In addition, the present disclosure provides a method of identifying a marker of an enteropathy, or lack thereof, in the small bowel of a subject in the small bowel of a subject, the method comprising: (1) capturing one or more frames of a video of the small bowel of the subject; (2) determining a level of villous atrophy to each of the one or more frames of the video; (3) assigning an injury score for each of the one or more frames of the video, wherein the injury score comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy; (4) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof, by calculating: (a) a curve fit to the injury score for each of the one or more frames of the video provided in Step (2), for the entirety of the small bowel of the subject, and using equally spaced points therein; and (b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (5) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more markers are indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0023] In addition, the present disclosure provides a method of identifying a marker of an enteropathy, or lack thereof, in the small bowel of a subject in the small bowel of a subject, the method comprising: (1) capturing one or more frames of a video of the small bowel of the subject using Video-Capsule Endoscopy (VCE); (2) determining a CeliacEnteropathy Villous Atrophy Scale (CE-VAST) score for each of the one or more frames of the video, wherein the CE-VAST score comprises a level of injury intensity ranging from 0- 3, wherein 0 is no visual villous atrophy; and wherein 3 is complete visual villous atrophy; (3) generating a Mucosal AtRophy Celiac Scale (MARCS) score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof, by calculating: (a) a curve fit to the CE-VAST score for each of the one or more frames of the video provided in Step (2), for the entirety of the small bowel of the subject, and using equally spaced points therein; and (b) a mean CE-VAST score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the MARCS score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more markers are indicative of one or more of: (i) Celiac disease (CeD), or a lack thereof; (ii) a level of severity of Celiac disease (CeD) for the entirety of the small bowel, or one or more ROI therein; (iii) a likely therapeutic or adverse response of a treatment for Celiac disease (CeD) for the entirety of the small bowel, or one or more ROI therein, in a subject in need thereof; or (iv) an actual therapeutic or adverse response of a treatment for Celiac disease (CeD) for the entirety of the small bowel, or one or more ROI therein, in a subject in need thereof.BRIEF DESCRIPTION OF THE DRAWINGS

[0024] FIG. 1 shows an ordinal scale of frame-wise villous injury. Here, the scale ranges from 0-3, wherein 0 = no visual villous atrophy; and 3 = complete villous atrophy.

[0025] FIG. 2 depicts an example marker of an enteropathy, plots of celiac injury intensity scores over the length of the small bowel (SB). Here, the position is represented as the fraction of the SB from the pyloric- duodenal junction to the ileocecal valve. Tertile 1 is shown as the blue shaded region.

[0026] FIG. 3 shows a diagram illustrating the intersection of biology, a given enteropathy, and a treatment thereof. For example, a therapeutically effective treatment may cause mechanism-specific changes to the biology of the small bowel (SB).

[0027] FIG. 4 shows the marker for Subject A (a healthy control with no known history of gastrointestinal disease). Image frame 1 out of 2571 is indicated by the vertical bar, and has an injury score of 0.48. Image frame 1 corresponds to the image shown in FIG. 5.The injury score (shown here as disease severity on the Y-axis) is an ordinal scale from 0-3 (wherein 0 = villous atrophy, 3 = severe or complete villous atrophy).

[0028] FIG. 5 shows an image frame obtained from Subject A via the PillCam.

[0029] FIG. 6 shows the marker for Subject B (subject exhibiting signs of an enteropathy, such as celiac disease). Image frame 1 out of 10393 is indicated by the vertical bar, and has an injury score of 2.57. Image frame 1 corresponds to the image shown in FIG.7. The injury score (shown here as disease severity on the Y-axis) is an ordinal scale from 0-3 (wherein 0 = villous atrophy, 3 = severe or complete villous atrophy).

[0030] FIG. 7 shows an image frame obtained from Subject B via the PillCam.

[0031] FIG. 8 shows a schematic view of an example computing device that may be used to implement the systems and methods described herein.

[0032] FIG. 9 shows a graphical user interface (GUI).

[0033] FIG. 10 shows the marker for Subject 1, a 55-year-old individual with a longstanding history of celiac disease who presented with intermittent severe gastrointestinal symptoms, which were exacerbated by accidental gluten exposure. The subject generally maintained good health but experienced flare-ups upon inadvertent gluten ingestion. Here, the marker for Subject 1 revealed mild to moderate villus atrophy in the proximal small bowel. Tertile 1 showed a smoothed minimum severity, smoothed mean severity, and smoothed maximum severity of 0.5, 0.80, and 1.1, respectively; tertile 2 showed smoothed minimum severity, smoothed mean severity, and smoothed maximum severity of 0.0, 0.09, and 0.7, respectively; and tertile 3 showed a smoothed minimum severity, smoothed mean severity, and smoothed maximum severity of 0.0, 0.01, and 0.0, respectively. SI Position = small bowel position from proximal end to distal end of the small bowel. Tertiles are indicated by vertical lines along X axis. The injury score (shown here as disease severity on the Y-axis) is an ordinal scale from 0-3 (wherein 0 = villous atrophy, 3 = severe or complete villous atrophy). The dashed line shows a trendline.

[0034] FIG. 11 shows the marker for Subject 2, a 19-year-old individual who was diagnosed with celiac disease following investigation for anemia. The subject reported only mild gastrointestinal symptoms at the time of diagnosis. The marker for Subject 2 revealed moderate to severe villus atrophy through the mid small bowel. Tertile 1 showed a smoothed minimum severity, smoothed mean severity, and smoothed maximum severity of 2.9, 2.90, and 2.9, respectively; tertile 2 showed a smoothed minimum severity, smoothed mean severity, and smoothed maximum severity of 0.3, 1.64, and 2.9, respectively; tertile 3 showed a smoothed minimum severity, smoothed mean severity, and smoothed maximum severity of0.0, 0.06, and 0.3, respectively. SI Position = small bowel position from proximal end to distal end of the small bowel. Tertiles are indicated by vertical lines along X axis. The injury score (shown here as disease severity on the Y-axis) is an ordinal scale from 0-3 (wherein 0 = villous atrophy, 3 = severe or complete villous atrophy). The dashed line shows a trendline.

[0035] FIG. 12 shows the marker for Subject 3, a 34-year-old individual with celiac disease who presented with persistent and severe gastrointestinal and extra-intestinal symptoms despite strict adherence to a gluten-free diet (GFD). Immune testing revealed markedly elevated levels of circulating gluten-responsive T cells, suggesting ongoing immune activation. Here, the marker for Subject 3 revealed severe villus atrophy throughout the small bowel. Tertile 1 showed a smoothed minimum severity, smoothed mean severity, and smoothed maximum severity of 2.8, 2.89, and 2.9, respectively; tertile 2 showed a smoothed minimum severity, smoothed mean severity, and smoothed maximum severity of 2.8, 2.85, and 2.9, respectively; tertile 3 showed a smoothed minimum severity, smoothed mean severity, and smoothed maximum severity of 1.9, 2.52, and 2.8, respectively. SI Position = small bowel position from proximal end to distal end of the small bowel. Tertiles are indicated by vertical lines along X axis. The injury score (shown here as disease severity on the Y-axis) is an ordinal scale from 0-3 (wherein 0 = villous atrophy, 3 = severe or complete villous atrophy). The dashed line shows a trendline.

[0036] FIG. 13 is a schematic diagram of an example environment for a computer- implemented comparator.

[0037] FIGS. 14A and 14B are schematic diagrams of example computer- implemented comparators as shown in FIG. 13.DETAILED DESCRIPTION

[0038] DEFINITIONS

[0039] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Accordingly, the following terms are intended to have the following meanings:

[0040] As used in the specification and claims, the singular form “a”, “an” and “the” includes plural references unless the context clearly dictates otherwise.

[0041] “Administering” or “administration” or “administer” means to dispense, provide, and / or apply, and refers to any route of administration. For example, administering can refer to, e.g., administration as a suppository, parenteral, intraperitoneal, intramuscular,intralesional, intrathecal, intracranial, intranasal or subcutaneous administration, or the implantation of a slow-release device, e.g., a mini-osmotic pump, to a subject. Administration can be by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal). In some embodiments, parenteral administration includes, e.g., intravenous, intramuscular, intra-arteriole, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, etc. By “co-administer” it is meant that a treatment as described herein is administered at the same time, just prior to, or just after the administration of one or more additional agents or therapies, also referred to herein as a “additional agent.” A treatment be administered alone or can be co- administered to the subject. Co-administration is meant to include simultaneous or sequential administration of the compound individually or in combination (more than one compound or agent).

[0042] “Ameliorate” or “amelioration” includes the arrest, prevention, decrease, or improvement in one or more the symptoms, signs, and features of the disease being treated, both temporary and long-term.

[0043] “Artificial intelligence approach” or “Al approach” refers to approaches, algorithms, architectures, and methodologies (e.g., machine learning approaches, etc.), that may be used to practice the methods of the present disclosure and / or any part or step thereof (e.g., assigning and / or determining an injury score; generating a summary score; generating a Mucosal AtRophy Celiac Scale (MARCS) score; and the like), and can include any one or more of: supervised learning (e.g., using logistic regression, using back propagation neural networks, using random forests, decision trees, etc.); unsupervised learning (e.g., using an Apriori algorithm, using K-means clustering); semi-supervised learning; a deep learning algorithm (e.g., neural networks, a restricted Boltzmann machine, a deep belief network method, a convolutional neural network method, a recurrent neural network method, stacked auto-encoder method, etc.); reinforcement learning (e.g., using a Q-learning algorithm, using temporal difference learning); a regression algorithm (e.g., ordinary least squares, logistic regression, stepwise regression, multivariate adaptive regression splines, locally estimated scatterplot smoothing, etc.); an instance-based method (e.g., k-nearest neighbor, learning vector quantization, self-organizing map, etc.); a regularization method (e.g., ridge regression, least absolute shrinkage and selection operator, elastic net, etc.); a decision tree learning method (e.g., classification and regression tree, iterative dichotomiser 3, C4.5, chi- squared automatic interaction detection, decision stump, random forest, multivariate adaptiveregression splines, gradient boosting machines, etc.); a Bayesian method (e.g., naive Bayes, averaged one-dependence estimators, Bayesian belief network, etc.); a kernel method (e.g., a support vector machine, a radial basis function, a linear discriminate analysis, etc.); a clustering method (e.g., k-means clustering, expectation maximization, etc.); an associated rule learning algorithm (e.g., an Apriori algorithm, an Eclat algorithm, etc.); an artificial neural network model (e.g., a Perceptron method, a back-propagation method, a Hopfield network method, a self-organizing map method, a learning vector quantization method, etc.); a dimensionality reduction method (e.g., principal component analysis, partial least squares regression, Sammon mapping, multidimensional scaling, projection pursuit, etc.); an ensemble method (e.g., boosting, bootstrapped aggregation, AdaBoost, stacked generalization, gradient boosting machine method, random forest method, etc.); and / or any suitable artificial intelligence approach.

[0044] “Indicators of small bowel injury” refer to any substance, number, or ratio derived from a series of observed facts relating to the status of injury in the small bowel of a subject, and that may reveal relative changes as a function of time. In some embodiments, an “indicator of small bowel injury” can be any observation, signal, sign, mark, note, or symptom that is visible and / or measurable, and evidences the existence or presence thereof. For example, in some embodiments, one or more indicators of small bowel injury can be a villous height / crypt depth (Vh:Cd) ratio; an enzyme-linked immunosorbent spot (ELISpot) assay; an IL-2 serology assay; a CD4 assay; a CD8 assay; an intraepithelial lymphocytes (IEL) count; a Marsh score; a patient-reported outcome assessment; or villous atrophy.

[0045] ‘Celiac disease” refers to a small bowel disorder characterized by mucosal inflammation, villous atrophy, and crypt hyperplasia, which may occur upon exposure of the small bowel to dietary gluten.

[0046] “Combination” refers to simultaneous, separate, or sequential administration. For example, in some embodiments, “combination” refers to simultaneous administration. In another embodiment, “combination” refers to separate administration. In a further embodiments, of the invention “combination” refers to sequential administration. Where the administration is sequential or separate, the delay in administering the second component should not be such as to lose the beneficial effect of the combination.

[0047] “Decreasing” or “decrease” or “decreased” or “reducing” or “reduced” or “a reduction” or “inhibiting” or any variation of these terms, refers to making something (e.g., a level of severity of a disease and / or an injury to the small bowel, or one or more ROI therein) less in size, amount, intensity, or degree. For example, in some embodiments, a “decrease” or“reduction” in a disease and / or injury to the small bowel, or the one or more ROI therein, can refer to the arrest, prevention, decrease, or improvement in one or more the symptoms, signs, and features of the disease and / or injury to the small bowel, or the one or more ROI therein. Accordingly, in some embodiments, a “decrease” or “reduction” in an enteropathy, can refer to the arrest, prevention, decrease, or improvement in one or more the symptoms, signs, and features of the enteropathy.

[0048] In some embodiments, the administration of a therapeutically effective amount of a treatment, to a subject in need thereof, results in one or more of the following effects: a decrease in the level of severity of a disease and / or injury to the small bowel, or the one or more ROI therein; a decrease in the occurrence of a disease and / or injury to the small bowel, or the one or more ROI therein; a decrease in the number and / or severity of one or more symptoms of a disease and / or injury to the small bowel, or one or more ROI therein; a decrease and / or reduction in the type and / or level of pain associated with a disease and / or injury to the small bowel, or the one or more ROI therein, in a subject who has been administered the therapeutically effective amount of the treatment — relative to the level of severity of a disease and / or injury to the small bowel, or the one or more ROI therein; the occurrence of a disease and / or injury to the small bowel, or the one or more ROI therein; the number and / or severity of one or more symptoms of a disease and / or injury to the small bowel, or one or more ROI therein; and / or the type and / or level of pain associated with a disease and / or injury to the small bowel, or the one or more ROI therein; in (1) the subject prior to being administered the therapeutically effective amount of the treatment; or (2) in a subject that has not been administered the therapeutically effective amount of the treatment.

[0049] In some embodiments, reducing or decreasing, includes any measurable decrease or complete inhibition to achieve a desired result. For example, there may be a decrease of about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or more, of the level and / or extent and / or symptoms of a disease and / or injury to the small bowel, or the one or more ROI therein, compared to normal. About as used herein means within ± 10%, preferably ± 5% of a given value. Thus, in some embodiments, the terms “reduction in the level of a disease and / or injury to the small bowel, or the one or more ROI therein,” refers to a decrease or reduction in the amount or level of disease and / or injury to the small bowel, or the one or more ROI therein, experienced by a subject who has received a therapeutically effective amount of a treatment, that is at least about 0.1%, at least about 0.2%, at least about 0.3%, at least about 0.4%, at least about 0.5%, at least about 0.6%, at least about 0.7%, atleast about 0.8%, at least about 0.9%, at least about 1%, at least about 1.25%, at least about 1.5%, at least about 1.75%, at least about 2%, at least about 2.25%, at least about 2.5%, at least about 2.75%, at least about 3%, at least about 3.25%, at least about 3.5%, at least about 3.75%, at least about 4%, at least about 4.25%, at least about 4.5%, at least about 4.75%, at least about 5%, at least about 5.25%, at least about 5.5%, at least about 5.75%, at least about 6%, at least about 6.25%, at least about 6.5%, at least about 6.75%, at least about 7%, at least about 7.25%, at least about 7.5%, at least about 7.75%, at least about 8%, at least about 8.25%, at least about 8.5%, at least about 8.75%, at least about 9%, at least about 9.25%, at least about 9.5%, at least about 9.75%, at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, at least about 15%, at least about 16%, at least about 17%, at least about 18%, at least about 19%, at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, at least about 42%, at least about 43%, at least about 44%, at least about 45%, at least about 46%, at least about 47%, at least about 48%, at least about 49%, at least about 50%, at least about 50%, at least about 51%, at least about 52%, at least about 53%, at least about 54%, at least about 55%, at least about 56%, at least about 57%, at least about 58%, at least about 59%, at least about 60%, at least about 61%, at least about 62%, at least about 63%, at least about 64%, at least about 65%, at least about 66%, at least about 67%, at least about 68%, at least about 69%, at least about 70%, at least about 71%, at least about 72%, at least about 73%, at least about 74%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 100%, or a greater than a 100%, relative to the amount or level of a disease and / or injury to the small bowel, or the one or more ROI therein, experienced by the subject prior to being administered the therapeutically effective amount of a treatment.

[0050] “Enteropathy” or “enteropathies” (plural) or “a disease of and / or injury to the small bowel, or the one or more ROI therein” all refer to any disease of, and / or injury to, the small bowel, and / or one or more regions of interest (ROI) therein. For example, in some embodiments, the term “enteropathy” can refer to a disease of the small bowel (e.g., celiac disease), wherein the disease affects the entirety of the small bowel, or one or more ROI therein. In yet other embodiments, the term “enteropathy” can refer to an injury to the smallbowel (e.g., mild, moderate or severe villus atrophy), wherein the injury affects the entirety of the small bowel, or one or more ROI therein.

[0051] In some embodiments, an enteropathy of the present disclosure can be a disease of, or injury to: (1) the entirety of the small bowel; (2) one or more regions of interest (ROI) of the small bowel; or (3) a combination thereof; wherein the disease or injury is: celiac disease (CeD); adenocarcinoma; amyloidosis; antibiotic associated diarrhea; arteriovenous malformations; bleeding ulcers; cancer; chronic granulomatous disease; collagenous colitis; colitis associated with radiotherapy or chemotherapy; colitis associated with disorders of innate immunity as in leukocyte adhesion deficiency- 1; Crohn’s disease (e.g., active Crohn's disease, refractory Crohn's disease, or fistulizing Crohn's disease); diversion colitis; diverticulitis; drug-induced enteropathy; drug or chemical-induced colitis; dysbiotic enteropathy; dysmotility; dyspepsia; eosinophilic gastroenteritis; enteropathy associated with seronegative arthropathies; familial polyposis; food allergies; functional gastrointestinal disorders; gastric hyperacidity; gastritis; gastroesophageal reflux disease; gastrointestinal inflammation caused by an infectious agent; gastroparesis; gluten disorders; hemolytic-uremic syndrome colitis; hemorrhagic colitis; indeterminate colitis; infection; infectious colitis; infectious gastritis or enterocolitis (e.g., Helicobacter pylo rz'-infected chronic active gastritis); inflammation; inflammatory bowel disease (IBD); intestinal lymphangiectasia; intestinal lymphoma; intestinal obstruction; iron deficiency anemia; irritable bowel syndrome; ischemic colitis; lactose intolerance; malabsorption; microscopic colitis; nonsteroidal anti-inflammatory drugs (NS AID) enteropathy; non-celiac gluten sensitivity (NCGS); nontropical Sprue; obscure bleeding; peptic ulcers; Peutz-Jeghers syndrome; pouchitis; protein-losing enteropathy; pseudo-obstruction; pseudomembranous colitis; regional enteritis; short-bowel (anastomosis) syndrome; small intestinal bacterial overgrowth; stress ulcers; ulcers; ulcerative colitis; Whipple’s disease; or Zollinger-Ellison syndrome.

[0052] In some embodiments, a symptom of an enteropathy of the present disclosure can be one or more of the following: abdominal bloating; abdominal distension; abdominal pain; anemia; anxiety; bloating; blood in stool or vomit; bruising easily; constipation; defects in tooth enamel; delayed puberty; dental enamel hypoplasia; depression; dermatitis; dermatitis herpetiformis; diarrhea (recurrent); diarrhea (chronic); excessive gas; fatigue; folate or vitamin B12 deficiency; gas; growth delay in children; hair loss; hemorrhage; idiopathic peripheral neuropathy; increased intraepithelial lymphocytes with crypt hyperplasia; indigestion; iron deficiency anemia; ischemia; joint pain; low birthweightoffspring; malabsorption; metabolic bone disease; missed menstrual periods; mouth ulcers; muscle cramps; nausea; neurological symptoms, e.g., ataxia or paresthesia; nonhereditary cerebellar ataxia; nosebleeds; pain; persistent aphthous stomatitis; persistent elevation in serum aminotransferases; premature osteoporosis; recurrent headaches; recurrent fetal loss; reduced fertility; seizures; sudden and / or unexpected weight loss; swollen, painful belly; tingling or numbness in hands or feet; weight loss; mild, moderate or severe villus atrophy with crypt hyperplasia; or vomiting.

[0053] “Generating a representation” refers to the process of creating a visual, auditory, or tactile output that conveys the information obtained via the methods described herein, e.g., the identity of one or more markers of an enteropathy in a subject, or lack thereof.

[0054] In some embodiments, a representation can be a visual representation, e.g., a graph or chart (e.g., bar graphs, line graphs, pie charts, scatter plots, heat maps, and other graphical representations); a numerical displays (e.g., showing scores or ratings in numerical formats, possibly with accompanying text or symbols); color-coded systems (e.g., utilizing colors to indicate different score ranges or categories); an iconographic Display (e.g., using icons or symbols to represent scores or related data; and / or an interactive visualizations (e.g., a dynamic representation that allows user interaction, such as zooming, rotating, or selecting parts for more detailed information). In some embodiments, a representation can be provided in a digital or electronic format. In other embodiments, a representation can be provided in a printed or physical format, e.g., a printed report or paper-based representation.

[0055] In some embodiments, the representation is presented as a comprehensible and interpretable form. For example, in some embodiments, method of the present disclosure comprises identifying one or more markers of an enteropathy, or lack thereof, in a subject, the method comprising: (1) assessing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury; and (3) generating a summary score of the injury score; wherein the summary score is generated by determining: (a) a curve fit to the injury score for the entirety of the small bowel of the subject, and using equally spaced points therein; and (b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (5) generating a graphical representation of the summary score.

[0056] In some embodiments, the representation can be generated by data processing hardware. In some embodiments, the representation can be a graphical representation,wherein the graphical representation is displayed on a graphical user interface as a curve, wherein each coordinate on the curve corresponds to a respective injury score, for a respective region of interest at a relative position within the small bowel.

[0057] ‘Indicative of’ or “associated with” with respect to a disease or condition (e.g., an enteropathy) means that a symptom, measurement, characteristic, or status in question is linked to the diagnosis, development, presence, or progression of that disease or condition. As association can, but need not, be causatively linked to the disease. For example, in some embodiments, signs, sequelae, and / or any effects causing any one or more symptoms of an enteropathy, can be considered indicative of that enteropathy. Recognition and identification of enteropathies based upon clinical presentation, and the signs, sequelae, and / or any effects thereof, are described herein, and can be performed by those skilled in the art. Methods of identifying enteropathies based on symptomatology are well known in the art. And, the recognition of the clinical presentation of enteropathies is well within the purview of one having ordinary skill in the art, and who can perform suitable clinical, diagnostic, and / or observational or other techniques required.

[0058] ‘Indicator,” as used herein (e.g., indicator of small bowel injury), refers to any one or more observations, substances, measurements, signals, signs, symptoms, or ratios that can be derived from objectively measurable entities or observed facts that are, e.g., in some embodiments, visible, detectable, and / or measurable; and wherein the presence, absence, or pattern of said indicators can be used to generate a marker of the present disclosure. “Indicators of small bowel injury” refer to any one or more observations, substances, measurements, signals, signs, symptoms, or ratios related to small bowel health that can be derived from objectively measurable entities or observed facts that are, e.g., in some embodiments, visible, detectable, and / or measurable. For example, in some embodiments, an “indicator of small bowel injury” can be: a villous height / crypt depth (Vh:Cd) ratio; an enzyme-linked immunosorbent spot (ELISpot) assay; an IL-2 serology assay; a CD4 assay; a CD8 assay; an intraepithelial lymphocytes (IEL) count; a Marsh score; a patient-reported outcome assessment; or villous atrophy. In some embodiments, a marker

[0059] ‘Indicators of small bowel injury” refer to any one or more observations, substances, measurements, signals, signs, symptoms, or ratios — related to small bowel health and / or small bowel injury — that can be derived from objectively measurable entities or observed facts that are, e.g., in some embodiments, visible, detectable, and / or measurable. In some embodiments, an “indicator of small bowel injury” can be: a villous height / crypt depth (Vh:Cd) ratio; an enzyme-linked immunosorbent spot (ELISpot) assay; an IL-2 serologyassay; a CD4 assay; a CD8 assay; an intraepithelial lymphocytes (IEL) count; a Marsh score; a patient-reported outcome assessment; or villous atrophy.

[0060] “Marker” or “marker of an enteropathy,” as used herein, refers to an output, outcome, recapitulation, summary, or signature arising from, measured, or calculated based on an analysis and / or evaluation of the presence, absence, or pattern, of one or more indicators (e.g., indicators of small bowel injury); wherein the marker reveals, is reflective of, or is indicative of: the presence or absence of a given condition (e.g., the presence of an enteropathy, or lack thereof); the level of severity of a condition (e.g., the level of severity of an enteropathy); changes to the level of severity of a condition, as determined spatially, temporally, or a combination thereof; whether a subject in need of treatment is likely to have a therapeutic or adverse response to said treatment; and / or whether a subject in need of treatment is experiencing an actual therapeutic or adverse response to a treatment. The term “indicator,” as used herein (e.g., an “indicator of small bowel injury”), refers to any one or more observations, substances, measurements, signals, signs, symptoms, or ratios that can be derived from objectively measurable entities or observed facts that are, e.g., in some embodiments, visible, detectable, and / or measurable.

[0061] For example, in some embodiments, a “marker” of the present disclosure is the output, outcome, recapitulation, summary, or signature arising from an analysis of the pattern of indicators observed in a subject (e.g., indicators of small bowel injury observed in a subject), wherein the “marker” — i.e., the summary of the pattern of the indicators observed — produces an output or signature that indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0062] In some embodiments, a marker of the present disclosure is an output, outcome, recapitulation, summary, or signature arising from, measured, or calculated based on an analysis and / or evaluation of the presence, absence, or pattern, of one or more indicators (e.g., indicators of small bowel injury); wherein the marker, i.e., the output, outcome, recapitulation, summary, or signature is calculated, represented, reported, and / or communicated as a graphical representation, e.g., such a as a curve.

[0063] Accordingly, in some embodiments, a marker of the present disclosure is represented as a curve, wherein the morphology of the curve (e.g., shape, slope, curvature, inflection point, tangent, concavity, asymptote, intercept, maximum, minimum, extremum, zero crossing, curvature radius, arc length, chord, vertex, perimeter, area under the curve,vertex angle, endpoint, etc.) is indicative of the presence or absence of a given condition (e.g., the presence of an enteropathy, or lack thereof); the level of severity of a condition (e.g., the level of severity of an enteropathy); changes to the level of severity of a condition, as determined spatially, temporally, or a combination thereof; whether a subject in need of treatment is likely to have a therapeutic or adverse response to said treatment; and / or whether a subject in need of treatment is experiencing an actual therapeutic or adverse response to a treatment.

[0064] In some embodiments, a marker of the present disclosure can be a biomarker or a data-driven marker. “Biomarker” as used herein can refer to one or more indicators that are associated quantitatively and / or qualitatively with: a biological change; an indication characterizing a phenotype; an objectively measurable entity which serves as an indicator of a biological state; a molecular indicator of a specific biological property; and / or biochemical feature, or pattern thereof, that can be used to determine the presence or absence and / or severity of a particular state, condition, disease, and / or response to a therapeutic intervention. “Data-driven marker” refers to one or more quantitative measures discovered under a data- driven framework based on one or more indicators, wherein said measures are evident as patterns irrespective of a ground truth basis.

[0065] In some embodiments, a marker of the present disclosure, identifiable pursuant to the methods described herein, can be a summary of damage or injury (as determined based on the level or intensity of an indicator such as villous atrophy) along the entire small bowel of a subject and / or one or more regions of interest (ROI) therein; wherein the summary of damage is represented / displayed as a graphical representation, e.g., such a as a curve, wherein the morphology of the curve (e.g., shape, slope, etc. of the curve) produces a signature indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0066] “Processing” refers to a wide array of operations, techniques, and methodologies performed by data processing hardware, and known by those having ordinary skill in the art. For example, in some embodiments, processing includes, but is not limited to: image analysis techniques (e.g., pixel analysis, edge detection, feature extraction, and / or segmentation); data transformation operations (e.g., filtering, scaling and resizing, and color space conversion); algorithmic processing (e.g., machine learning algorithms, pattern recognition, and neural networks); statistical analysis (e.g., quantitative analysis, and / orcomparative analysis) data integration and synthesis (e.g., multi-modal data processing, and / or synthesis of findings); automated decision making (e.g., rule-based systems, and / or adaptive algorithms); graphical processing (e.g., visualization techniques, 3D reconstruction); hardware-specific operations (e.g., parallel processing, GPU acceleration, and the like); postprocessing operations (e.g., error checking, and data optimization).

[0067] ‘ROI” or “regions of interest” refers to any one or more loci or points along the small bowel. In some embodiments, the one or more ROI are of interest because they are reflective of a specific mechanism of injury (e.g., as correlated or corresponding to a specific enteropathy) and / or are indicative of a mechanism specific response or healing pattern that can be associated with one or more treatments. For example, in some embodiments, one or more ROI can be one or more loci in the proximal or distal portion of the small bowel, wherein said ROI are indicative of some mechanism specific response to an enteropathy, or the treatment thereof. In some embodiments, and without limitation, a candidate treatment may be known to affect only the proximal part of the small bowel: thus, an ROI in such a case may be one or more points along the proximal part of the small bowel.

[0068] In some embodiments, an ROI can be 60 or more equally spaced points along the length of the small bowel. In other embodiments, an ROI can be a first or proximal tertile. In other embodiments, an ROI can be a second or midline tertile. In yet other embodiments, an ROI can be a third or distal tertile.

[0069] ‘Small bowel” or “SB” or “small intestine” (used interchangeably) refers to the organ extending from the stomach to the large intestine, and any regions of interest (ROI) therein, i.e., in the craniocaudally direction, the three areas known as the duodenum jejunum and ileum, and included between two biologic valves, namely the pylorus and the ileocaecal valve. In some embodiments, the term “small bowel” can refer to the entirety of the small bowel, or any one or more loci contained therein. For example, in some embodiments, the term “small bowel” can refer to the entirety of the small bowel; in other embodiments, the term “small bowel” can refer to one or more of the duodenum, jejunum, and / or ileum. And, in yet other embodiments, the term “small bowel” can refer to any one or more regions of interest contained within the small bowel.

[0070] ‘Reference subject” refers to any animal (e.g., a mammal, such as a human) from which one or more reference markers may be obtained, wherein said one or more reference markers can be used as comparators in order to: identify one or more markers in the small bowel of a subject (a non-reference or test subject, such as subject for whom diagnosis, prognosis, and / or treatment is desired); diagnose an enteropathy in the subject; determine alevel of severity of an enteropathy in the subject; identify a biological response to one or more treatments for an enteropathy in the subject; or identify one or more treatments for an enteropathy in the subject. In some embodiments, there can be multiple reference subjects, each comprising multiple reference markers, e.g., a first reference subject, a second reference subject, a third reference subject, a fourth reference subject, a fifth reference subject, a sixth reference subject, a seventh reference subject, and eighth reference subject, a ninth reference subject, a tenth reference subject, and so on; wherein each of the reference subjects has corresponding markers indicative of the presence or absence of a condition. For example, in some embodiments, a reference subject can have one or more reference markers indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0071] “Subject” or “patient” or “participant” are used herein interchangeably, and refer to any animal (e.g., a mammal, such as a human) for whom diagnosis, prognosis, and / or treatment is desired. For example, in some embodiments, a subject can be a mammal, e.g., a human or non-human primate (such as an ape, monkey, orangutan, or chimpanzee), a dog, cat, guinea pig, rabbit, rat, mouse, horse, cattle, or cow. In certain embodiments, a “subject in need thereof’ refers to one or more of the following: a subject diagnosed with a disease and / or injury to the small bowel, or the one or more ROI therein, and / or is exhibiting one or more conditions or symptoms associated with a disease and / or injury to the small bowel, or the one or more ROI therein; a subject who has been diagnosed with or exhibited one or more conditions associated with a disease and / or injury to the small bowel, or the one or more ROI therein in the past; or a subject who has been deemed at risk of developing a disease and / or injury to the small bowel, or the one or more ROI therein, or one or more conditions associated with a disease of and / or injury to the small bowel, or the one or more ROI therein, in the future due to hereditary, lifestyle, and / or environmental factors.

[0072] “Therapeutically effective amount” or “effective amount” or “pharmaceutically effective amount” refer to a nontoxic but sufficient amount of a treatment, or — where applicable — a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition comprising the same, to provide the desired biological result, and / or to an amount sufficient to carry out a specifically stated purpose.

[0073] In some embodiments, the term “therapeutically effective amount” refers to an amount of a treatment, or a pharmaceutical composition comprising the same, which is effective to “treat” a disease or condition (e.g., an enteropathy) in a subject (e.g., a mammalsuch as a human), and provides some improvement or benefit to a subject having the disease or condition (e.g., an enteropathy). Thus, a “therapeutically effective” amount is an amount that provides some alleviation, mitigation, and / or decrease in at least one clinical symptom of a disease of and / or injury to the small bowel, or the one or more ROI therein. Clinical symptoms associated with the diseases or conditions that can be treated by the methods of the disclosure are known in the art and described herein. Further, therapeutic effects need not be complete or curative, as long as some benefit is provided to the subject.

[0074] In some embodiments, the term “therapeutically effective” refers to an amount of a therapeutic agent that is capable of alleviation or amelioration of one or more symptoms or conditions; diminishment of extent of condition, disorder or disease; stabilization of the state of condition, disorder, or disease; prevention of development of condition, disorder, or disease; prevention of spread of condition, disorder, or disease; delay or slowing of condition, disorder, or disease progression; delay or slowing of condition, disorder, or disease onset; amelioration or palliation of the condition, disorder, or disease state, and remission; limiting the symptoms of the condition, disorder, or disease state; reducing the severity of the condition, disorder, or disease state and / or any one or more symptoms associated thereof; relieving the pain associated with and / or caused by the condition, disorder, or disease state; whether partial or total, in a subject in need thereof.

[0075] In some embodiments, a “therapeutically effective amount” can be determined empirically and in a routine manner, in relation to the stated purpose. And, an appropriate therapeutically effective amount in any individual case may be determined by one of ordinary skill in the art using routine experimentation. The actual amount administered and rate and time-course of administration, will depend on the nature and severity of what is being treated. Prescription of treatment, e.g., decisions on dosage etc., is within the responsibility of general practitioners and other medical doctors.

[0076] In some embodiments, a “therapeutically effective amount” can be an amount sufficient for a treatment to accomplish a stated purpose relative to the absence of the treatment (e.g., achieve the effect for which it is administered, treat a disease, reduce enzyme activity, increase enzyme activity, reduce a signaling pathway, and / or reduce one or more symptoms of a disease or condition). In one embodiment, an example of a “therapeutically effective amount” is an amount sufficient to contribute to the treatment, prevention, or reduction of a symptom or symptoms of a disease, condition, or symptom associated thereof (e.g., a disease of and / or injury to the small bowel, or the one or more ROI therein). In some embodiments, a “reduction” of a symptom or symptoms (and grammatical equivalents of thisphrase) means decreasing of the severity or frequency of the symptom(s), or elimination of the symptom(s), either in whole or in part.

[0077] In some embodiments, a “therapeutically effective amount” can be an amount that has a prophylactic effect, e.g., an amount of a treatment that, when administered to a subject, will have the intended prophylactic effect, e.g., preventing or delaying the onset (or reoccurrence) of an injury, disease, pathology or condition, or reducing the likelihood of the onset (or reoccurrence) of an injury, disease, pathology, or condition, or one or more symptoms associated thereof. The full prophylactic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses. Thus, a prophylactically effective amount may be administered in one or more administrations.

[0078] In some embodiments, a “therapeutically effective amount” can be an amount that results in a decrease in activity (e.g., an “activity decreasing amount”). In some embodiments, an activity decreasing amount can be an amount of a treatment that, when administered to a subject, decreases the activity of a molecule (e.g., an enzyme) relative to the absence of the treatment.

[0079] In some embodiments, a “therapeutically effective amount” can be an amount that results in an increase in activity (e.g., an “activity increasing amount”). In some embodiments, an activity decreasing amount can be an amount of a treatment that, when administered to a subject, increases the activity of molecule (e.g., an enzyme) relative to the absence of the treatment.

[0080] “Treatment” or “treatment of’ a condition, disease or disorder or symptoms associated with a condition, disease or disorder refers to an approach for obtaining beneficial or desired results, including clinical results. Beneficial or desired clinical results can include, but are not limited to: alleviation or amelioration of one or more symptoms or conditions; diminishment of extent of condition, disorder or disease; stabilization of the state of condition, disorder, or disease; prevention of development of condition, disorder, or disease; prevention of spread of condition, disorder, or disease; delay or slowing of condition, disorder, or disease progression; delay or slowing of condition, disorder, or disease onset; amelioration or palliation of the condition, disorder or disease state, and remission; limiting the symptoms of the condition, disorder, or disease state; reducing the severity of the condition, disorder, or disease state and / or any one or more symptoms associated thereof; relieving the pain associated with and / or caused by the condition, disorder or disease state; whether partial or total.

[0081] “Treating” or “reducing” or “inhibiting” or “limiting” or any variation of these terms, refers to making something (e.g., the number of symptoms; severity of symptoms and / or injury; and / or frequency of symptoms, such as degree / severity of pain and / or frequency of pain) less in size, amount, intensity, or degree. For example, in some embodiments, the administration of a therapeutically effective amount a treatment, to a subject in need thereof, results in the following effect: a decrease in the frequency and / or severity of one or more symptoms or pain associated with a disease of and / or injury to the small bowel, or the one or more ROI therein (an enteropathy); a decrease in the frequency and / or severity of one or more symptoms or pains associated with an enteropathy, e.g., celiac disease; a decrease in the frequency of and / or severity of and / or occurrence of one or more symptoms of or pains associated with an enteropathy; a decrease in the frequency of and / or severity of and / or occurrence of one or more symptoms of or pains associated with celiac disease; or any combination thereof — relative to the number, frequency, and / or severity of any of the foregoing symptoms, injuries, and / or pains in a subject that has not been administered a therapeutically effective amount of the treatment as described herein.

[0082] In some embodiments, limiting the symptoms of, reducing the severity of, or treating a disease of and / or injury to the small bowel, or the one or more ROI therein, e.g., an enteropathy such as celiac disease, and / or a symptom or a pain associated thereof, includes any measurable decrease or complete inhibition to achieve a desired result. For example, there may be a decrease of about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or more, in the number of symptoms, severity of symptoms / injury, and / or frequency of symptoms (e.g., number, severity, and / or frequency of symptoms and / or pain associated with a disease of and / or injury to the small bowel, or the one or more ROI therein, e.g., celiac disease). About as used herein means within ± 10%, preferably ± 5% of a given value.

[0083] Thus, in some embodiments, the terms “limiting the symptoms of,” or “reducing the severity of,” or “treating a disease of and / or injury to the small bowel, or the one or more ROI therein,” can refer to: a decrease or reduction in the frequency and / or severity of a symptom and / or pain associated with a disease of and / or injury to the small bowel, or the one or more ROI therein, when a therapeutically effective amount of a treatment is administered to a subject in need thereof, that is at least about 0.1%, at least about 0.2%, at least about 0.3%, at least about 0.4%, at least about 0.5%, at least about 0.6%, at least about 0.7%, at least about 0.8%, at least about 0.9%, at least about 1%, at least about 1.25%, at least about 1.5%, at least about 1.75%, at least about 2%, at least about 2.25%, atleast about 2.5%, at least about 2.75%, at least about 3%, at least about 3.25%, at least about 3.5%, at least about 3.75%, at least about 4%, at least about 4.25%, at least about 4.5%, at least about 4.75%, at least about 5%, at least about 5.25%, at least about 5.5%, at least about 5.75%, at least about 6%, at least about 6.25%, at least about 6.5%, at least about 6.75%, at least about 7%, at least about 7.25%, at least about 7.5%, at least about 7.75%, at least about 8%, at least about 8.25%, at least about 8.5%, at least about 8.75%, at least about 9%, at least about 9.25%, at least about 9.5%, at least about 9.75%, at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, at least about 15%, at least about 16%, at least about 17%, at least about 18%, at least about 19%, at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, at least about 42%, at least about 43%, at least about 44%, at least about 45%, at least about 46%, at least about 47%, at least about 48%, at least about 49%, at least about 50%, at least about 50%, at least about 51%, at least about 52%, at least about 53%, at least about 54%, at least about 55%, at least about 56%, at least about 57%, at least about 58%, at least about 59%, at least about 60%, at least about 61%, at least about 62%, at least about 63%, at least about 64%, at least about 65%, at least about 66%, at least about 67%, at least about 68%, at least about 69%, at least about 70%, at least about 71%, at least about 72%, at least about 73%, at least about 74%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 100%, or a greater than a 100%, relative to the frequency and / or severity of a symptom and / or a pain associated with a disease of and / or injury to the small bowel, or the one or more ROI therein, in the subject prior to being administered the treatment; or in a subject that has not received a therapeutically effective amount of the treatment.

[0084] In some embodiments, “treating” can also mean prolonging survival of a subject beyond that expected in the absence of treatment. “Treating” can also mean inhibiting the progression of the condition, disorder or disease, slowing the progression of the condition, disorder or disease temporarily, although in some instances, it involves halting the progression of the condition, disorder or disease permanently. As used herein the terms treatment, treat, or treating refers to a method of reducing the effects of one or more symptoms of a disease or condition. Thus, in some embodiments, treatment can refer to a 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or100% reduction in the severity of an established disease, condition, or symptom of the disease or condition. For example, a method for treating a disease is considered to be a treatment if there is a 10% reduction in one or more symptoms of the disease in a subject as compared to a control. Thus the reduction can be a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or any percent reduction in between 10% and 100% as compared to native or control levels. It is understood that treatment does not necessarily refer to a cure or complete ablation of the disease, condition, or symptoms of the disease or condition. Further, as used herein, references to decreasing, reducing, or inhibiting include a change of 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or greater as compared to a control level and such terms can include but do not necessarily include complete elimination.

[0085] ‘Villous atrophy” refers to an indicator of small bowel injury, and is a morphological alteration characterized by the flattening or diminution of intestinal villi. In some embodiments, villous atrophy can be visually assessed based on the villi's structure, and / or the height-to-crypt depth ratio. In some embodiments, the visual presentation of villous atrophy reveals diminished and flattened villi, often accompanied by crypt hyperplasia and / or increased presence of intraepithelial lymphocytes.

[0086] In some embodiments, the level of villous atrophy (i.e., level of injury) can be scored using an ordinal scale. In some embodiments, the level of injury ranges from 0-10, wherein 0 corresponds to no villous atrophy; and wherein 10 corresponds to complete villous atrophy; from 0-9, wherein 0 corresponds to no villous atrophy; and wherein 9 corresponds to complete villous atrophy; from 0-8, wherein 0 corresponds to no villous atrophy; and wherein 8 corresponds to complete villous atrophy; from 0-7, wherein 0 corresponds to no villous atrophy; and wherein 7 corresponds to complete villous atrophy; from 0-6, wherein 0 corresponds to no villous atrophy; and wherein 6 corresponds to complete villous atrophy; from 0-5, wherein 0 corresponds to no villous atrophy; and wherein 5 corresponds to complete villous atrophy; from 0-4, wherein 0 corresponds to no villous atrophy; and wherein 4 corresponds to complete villous atrophy; or from 0-3 wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy.

[0087] ‘Visual assessment” refers to the perception, interpretation, and evaluation of visual information, which may include, but is not limited to: color, shape, size, texture, pattern, spatial relationships, and / or a level or degree of injury observed in the small bowel of a subject. In some embodiments, a visual assessment can be conducted either manually (e.g.,by human observers) or automatically (e.g., using image processing techniques and software algorithms designed to simulate, augment, or enhance human visual analysis).

[0088] In some embodiments, a visual assessment can include both qualitative and quantitative methods of evaluation, wherein qualitative methods may involve subjective judgment or comparison, and quantitative methods may involve measurements or calculations based on visual data.

[0089] In some embodiments, a visual assessment describes the perception, interpretation, and evaluation of visual information contained within one or more images, e.g., one or more photographic image frames; one or more sonographic image frames; one or more radiographic image frames; one or more confocal image frames; or one or more tomographic image frames. Accordingly, in some embodiments, a visual assessment describes the evaluation or analysis of an object, scenario, or condition based on visual cues or characteristics perceived through human sight or through the use of one or more devices.

[0090] In some embodiments, devices operable to perform a visual assessment include any instrument or apparatus designed to observe, analyze, measure, or interpret visual information. For example, in some embodiments, devices operable to perform a visual assessment include optical devices including, but is not limited to, devices equipped with lenses, mirrors, prisms, sensors, cameras, and other optical elements capable of capturing and manipulating light. In some embodiments, such optical devices may perform functions such as imaging, magnification, light intensity measurement, color analysis, pattern recognition, and / or spatial analysis. In some embodiments, optical devices operable to perform a visual assessment as described herein include: microscopes (e.g., compound, electron, fluorescence, confocal, polarizing, phase contrast, scanning tunneling, and the like); spectrophotometers; cameras (still, video, and the like); endoscopes (e.g., an enteroscope); and the like known to those having ordinary skill in the art.

[0091] In some embodiments, devices operable to perform a visual assessment may operate in a range of the electromagnetic spectrum, from ultraviolet to infrared, and may include capabilities for digital processing and interpretation of the captured visual data. In yet other embodiments, devices operable to perform a visual assessment may be standalone units or part of a larger system, incorporating hardware and software components for data acquisition, processing, analysis, and display. As described herein, the integration of artificial intelligence and machine learning algorithms for enhanced visual assessment and decisionmaking is also encompassed within the scope of this definition.

[0092] In some embodiments, a visual assessment can be the perception, interpretation, and evaluation of visual information contained within two or more image frames, e.g., two or more frames of a video. In some embodiments, the two or more image frames depict the small bowel circumferentially and / or proximodistally along the interior of the small bowel of the subject. In other embodiments, a plurality of images can depict the entire interior surface or lumen of the small bowel, wherein the plurality of images provide a 360 degree view of the lumen (e.g., a circumferential view) and / or a proximodistal view. In some embodiments, the plurality of images reflect the view of a camera wherein said camera is spiraling proximodistally in the small bowel.

[0093] Throughout this specification, unless specifically stated otherwise or the context requires otherwise, reference to a single step, composition of matter, group of steps or group of compositions of matter shall be taken to encompass one and a plurality (i.e., one or more) of those steps, compositions of matter, groups of steps or group of compositions of matter.

[0094] The present disclosure is performed without undue experimentation using, unless otherwise indicated, conventional techniques of molecular biology, microbiology, virology, recombinant DNA technology, solid phase and liquid nucleic acid synthesis, peptide synthesis in solution, solid phase peptide synthesis, immunology, cell culture, and formulation. Such procedures are described, for example, in Sambrook, Fritsch & Maniatis, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, New York, Second Edition (1989), whole of Vols I, II, and III; DNA Cloning: A Practical Approach, Vols. I and II (D. N. Glover, ed., 1985), IRL Press, Oxford, whole of text; Oligonucleotide Synthesis: A Practical Approach (M. J. Gait, ed, 1984) IRL Press, Oxford, whole of text, and particularly the papers therein by Gait, ppl-22; Atkinson et al, pp35-81; Sproat et al, pp 83- 115; and Wu et al, pp 135-151; 4. Nucleic Acid Hybridization: A Practical Approach (B. D. Hames & S. J. Higgins, eds., 1985) IRL Press, Oxford, whole of text; Immobilized Cells and Enzymes: A Practical Approach (1986) IRL Press, Oxford, whole of text; Perbal, B., A Practical Guide to Molecular Cloning (1984); Methods In Enzymology (S. Colowick and N. Kaplan, eds., Academic Press, Inc.), whole of series; J. F. Ramalho Ortigao, “The Chemistry of Peptide Synthesis” In: Knowledge database of Access to Virtual Laboratory website (Interactiva, Germany); Sakakibara, D., Teichman, J., Lien, E. Land Fenichel, R. L. (1976). Biochem. Biophys. Res. Commun. 73 336-342; Merrifield, R. B. (1963). J. Am. Chem. Soc. 85, 2149-2154; Barany, G. and Merrifield, R. B. (1979) in The Peptides (Gross, E. and Meienhofer, 3. eds.), vol. 2, pp. 1-284, Academic Press, New York. 12. Wiinsch, E., ed.(1974) Synthese von Peptiden in Houben-Weyls Metoden der Organischen Chemie (Muler, E., ed.), vol. 15, 4th edn., Parts 1 and 2, Thieme, Stuttgart; Bodanszky, M. (1984) Principles of Peptide Synthesis, Springer-Verlag, Heidelberg; Bodanszky, M. & Bodanszky, A. (1984) The Practice of Peptide Synthesis, Springer-Verlag, Heidelberg; Bodanszky, M. (1985) Int. J. Peptide Protein Res. 25, 449-474; Handbook of Experimental Immunology, Vols. I-IV (D. M. Weir and C. C. Blackwell, eds., 1986, Blackwell Scientific Publications); and Animal Cell Culture: Practical Approach, Third Edition (John R. W. Masters, ed., 2000); each of these references are incorporated herein by reference in their entireties.

[0095] Throughout this specification, unless the context requires otherwise, the word “comprise,” or variations such as “comprises” or “comprising,” will be understood to imply the inclusion of a stated step or element or integer or group of steps or elements or integers but not the exclusion of any other step or element or integer or group of elements or integers.

[0096] All patent applications, patents, and printed publications referred to herein are incorporated by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference in its entirety. And, all patent applications, patents, and printed publications cited herein are incorporated herein by reference in the entireties, except for any definitions, subject matter disclaimers, or disavowals, and except to the extent that the incorporated material is inconsistent with the express disclosure herein, in which case the language in this disclosure controls.

[0097] MARKERS

[0098] ‘Marker” or “marker of an enteropathy,” as used herein, refers to an outcome, recapitulation, summary, or signature arising from, measured, or calculated based on an analysis and / or evaluation of the presence, absence, or pattern, of one or more indicators (e.g., indicators of small bowel injury); wherein the marker reveals, is reflective of, or is indicative of: the presence or absence of a given condition (e.g., the presence of an enteropathy, or lack thereof); the level of severity of a condition (e.g., the level of severity of an enteropathy); changes to the level of severity of a condition, as determined spatially, temporally, or a combination thereof; whether a subject in need of treatment is likely to have a therapeutic or adverse response to said treatment; and / or whether a subject in need of treatment is experiencing an actual therapeutic or adverse response to a treatment. The term “indicator,” as used herein (e.g., an “indicator of small bowel injury”), refers to any one or more observations, substances, measurements, signals, signs, symptoms, or ratios that can bederived from objectively measurable entities or observed facts that are, e.g., in some embodiments, visible, detectable, and / or measurable.

[0099] For example, in some embodiments, a “marker” of the present disclosure is the outcome recapitulation, summary, or signature arising from an analysis of the pattern of indicators, e.g., indicators of small bowel injury, wherein the “marker” — i.e., the summary of the unique pattern of the indicators observed — produces a signature that indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0100] In some embodiments, a marker of the present disclosure is an output, outcome, recapitulation, summary, or signature arising from, measured, or calculated based on an analysis and / or evaluation of the presence, absence, or pattern, of one or more indicators (e.g., indicators of small bowel injury); wherein the marker, i.e., the output, outcome, recapitulation, summary, or signature is calculated, represented, reported, and / or communicated as a graphical representation, e.g., such a as a curve.

[0101] In some embodiments, a marker of the present disclosure is: (a) a curve fit to the injury score for the entirety of the small bowel of the subject, and using equally spaced points therein; and (b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof.

[0102] Accordingly, in some embodiments, a marker of the present disclosure is represented as a curve, wherein the morphology of the curve (e.g., shape, slope, curvature, inflection point, tangent, concavity, asymptote, intercept, maximum, minimum, extremum, zero crossing, curvature radius, arc length, chord, vertex, perimeter, area under the curve, vertex angle, endpoint, etc.) is indicative of the presence or absence of a given condition (e.g., the presence of an enteropathy, or lack thereof); the level of severity of a condition (e.g., the level of severity of an enteropathy); changes to the level of severity of a condition, as determined spatially, temporally, or a combination thereof; whether a subject in need of treatment is likely to have a therapeutic or adverse response to said treatment; and / or whether a subject in need of treatment is experiencing an actual therapeutic or adverse response to a treatment.

[0103] In some embodiments, a marker of the present disclosure can be a biomarker or a data-driven marker. “Biomarker” as used herein can refer to one or more indicators that are associated quantitatively and / or qualitatively with: a biological change; an indicationcharacterizing a phenotype; an objectively measurable entity which serves as an indicator of a biological state; a molecular indicator of a specific biological property; and / or biochemical feature, or pattern thereof, that can be used to determine the presence or absence and / or severity of a particular state, condition, disease, and / or response to a therapeutic intervention. “Data-driven marker” refers to one or more quantitative measures discovered under a data- driven framework based on one or more indicators, wherein said measures are evident as patterns irrespective of a ground truth basis.

[0104] In some embodiments, a marker of the present disclosure, identifiable pursuant to the methods described herein, can be a summary of damage or injury (as determined based on the level or intensity of an indicator such as villous atrophy) along the entire small bowel of a subject and / or one or more regions of interest (ROI) therein; wherein the summary of damage is represented / displayed as a graphical representation, e.g., such a as a curve, wherein the morphology of the curve (e.g., shape, slope, etc. of the curve) produces a signature indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0105] In some embodiments, a marker of the present disclosure can reflect, either quantitatively or qualitatively, one or more of the following: a biological change; a biologically-based marker of a condition; a biological marker characterizing a phenotype, or a pattern of indicators characterizing a phenotype; an objectively measurable entity which serves as an indicator of a biological state, or a pattern thereof; a molecular indicator of a specific biological property and / or biochemical feature, or pattern thereof, that can be used to determine the presence or absence and / or severity of a particular disease or condition; and / or a data-driven marker based on a pattern of any one or more indicators (e.g., spatially or temporally), as describe herein, wherein said data-driven marker can inform diagnosis and / or be used to recommend a treatment.

[0106] In some embodiments, a marker of the present disclosure can refer to the presence or pattern of one or more indicators, wherein the pattern has predictive, diagnostic, and / or prognostic value. In some embodiments, the pattern can be, e.g., a cluster of indicators (e.g., one or more indicators of small bowel injury such as: a villous height / crypt depth (Vh:Cd) ratio; an enzyme-linked immunosorbent spot (ELISpot) assay; an IL-2 serology assay; a CD4 assay; a CD8 assay; an intraepithelial lymphocytes (IEL) count; a Marsh score; a patient-reported outcome assessment; or villous atrophy); a temporal relationship betweenindicators (wherein the indicators are the same or different); a spatial relationship between indicators (wherein the indicators are the same or different); a cluster of symptoms; a temporal relationship of events; and / or any combination thereof.

[0107] In some embodiments, a marker of the present disclosure reflects a pattern observed for one or more indicators, wherein said marker can be used to enable more efficient and / or specific diagnoses by physicians and / or systems of disease activity, lack of activity, and / or bowel health. In other embodiments, a marker of the present disclosure can be a pattern observed for one or more indicators, wherein said marker can be combined with information contained in, e.g., a database of clinical information, wherein this combination can be used to enable more efficient and / or specific diagnoses by physicians and / or systems of disease activity, lack of activity, and / or bowel health.

[0108] In some embodiments, a marker of the present disclosure, identifiable pursuant to the methods described herein, can reflect a summary of damage or injury (as determined based on the level or intensity of an indicator such as villous atrophy) along the entire small bowel of a subject and / or one or more regions of interest (ROI) therein; wherein the summary of damage is represented / displayed as a curve, wherein the morphology of the curve (e.g., shape, slope, etc. of the curve) produces a pattern or signature indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy;(iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0109] In some embodiments, a marker of the present disclosure can be represented as a curve, wherein the morphology of the curve (e.g., shape, slope, etc.) produces a signature indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0110] In other embodiments, a marker of the present disclosure can be represented as a curve, wherein the morphology of the curve (e.g., shape, slope, etc.) produces a signature indicative of: (i) an enteropathy, or a lack thereof, in a subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or(iv) an actual therapeutic or adverse response to a treatment for an enteropathy; wherein the marker (i.e., the pattern or signature represented by the morphology of the curve) can be used to enable more efficient and / or specific diagnoses of disease activity, or lack thereof, and / oroverall patient bowel health; or can be used to recommend a treatment plan. An additional detailed description of markers is provided below.

[0111] In some embodiments, the marker may reflect a particular type or subtype of a disease, disorder, and / or injury, as characterized by certain molecular, pathological, histological, and / or clinical features. In other embodiments, the marker may reflect a baseline state (e.g., normal, healthy state). In yet other embodiments, the marker may reflect a disease of, or injury to the small bowel or one or more ROI therein (an enteropathy), in a subject. Alternatively, in some embodiments, the marker may reflect the absence of a disease of, or injury to the small bowel or one or more ROI therein (i.e., the absence of an enteropathy), in a subject.

[0112] In some embodiments, the marker may reflect a level of severity of a disease or condition, e.g., an enteropathy, or lack thereof. In some embodiments, the marker may reflect a likely therapeutic or adverse response to a treatment for a disease or condition, e.g., an enteropathy. In some embodiments, the marker may reflect an actual therapeutic or adverse response to a treatment for a disease or condition, e.g., enteropathy.

[0113] In some embodiments, a marker of the present disclosure can be a summary of damage (as determined, e.g., based on the level or intensity of villous atrophy and / or injury) along the entire small bowel of a subject and / or one or more regions of interest (ROI) therein. For example, in some embodiments, the summary of damage along the entire small bowel of a subject and / or one or more regions of interest (ROI) therein, can be determined according to the methods described herein, and reflected in graph; wherein the X-axis of the graph shows the position of injury along the small bowel; and the Y-axis shows the level of damage intensity.

[0114] Accordingly, in some embodiments, a marker of the present disclosure can be the summary of damage along the entire small bowel of a subject and / or one or more regions of interest (ROI) therein, as determined according to the methods described herein, and reflected in graph; wherein the X-axis shows the position of injury along the small bowel; and the Y-axis shows the level of damage intensity; and wherein the level of damage along the length of the small bowel is presented as a curve, which in turn reflects a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject.

[0115] In some embodiments, the marker can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve (e.g., shape, slope, etc.) produces a signature indicative of one or more of: (i) an enteropathy, or a lackthereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy. Accordingly, in some embodiments, a marker of the present disclosure can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve may be used to diagnose and / or identify an injury (e.g., an enteropathy) in the subject.

[0116] In some embodiments, a marker of the present disclosure can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve may be used to determine the level of severity of a disease and / or injury (e.g., an enteropathy).

[0117] In some embodiments, a marker of the present disclosure can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve may be used to identify a biological response to one or more treatments as described herein.

[0118] For example, in some embodiments, a marker of the present disclosure can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve may be used to identify a biological response to one or more treatments for an enteropathy in a subject; wherein the biological response is a likely therapeutic response to the one or more treatments for the enteropathy.

[0119] In some embodiments, a marker of the present disclosure can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve may be used to identify a biological response to one or more treatments for an enteropathy in a subject; wherein the biological response is a likely adverse response to the one or more treatments for the enteropathy.

[0120] In some embodiments, a marker of the present disclosure can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve may be used to identify a biological response to one or more treatments for an enteropathy in a subject; wherein the biological response is an actual therapeutic response to the one or more treatments for the enteropathy.

[0121] In some embodiments, a marker of the present disclosure can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve may be used to identify a biological response to one or more treatments for an enteropathy in a subject; wherein the biological response is an actual adverse response to the one or more treatments for the enteropathy.

[0122] In some embodiments, a marker of the present disclosure can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve may be used to identify a biological response to one or more treatments for an enteropathy in a subject; wherein the biological response is an improvement to a level of severity, or lack thereof, of the enteropathy; wherein the improvement or lack thereof is determined spatially, temporally, or a combination thereof.

[0123] For example, in some embodiments, a marker of the present disclosure can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve can be tracked in a spatiotemporal manner, wherein the change to the morphology of the curve may be used to implicate a treatments mechanism of action.

[0124] In some embodiments, a marker of the present disclosure can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve can be tracked in a spatiotemporal manner, and wherein the morphology of the curve may be used to identify the distribution and / or intensity of disease as a subgroup.

[0125] In yet other embodiments, a marker of the present disclosure can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve can be tracked in a spatiotemporal manner, and wherein the change to the morphology of the curve may be used to deduce the pharmacokinetics of a drug.

[0126] In some embodiments, a marker of the present disclosure can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve can be tracked in a spatiotemporal manner, and wherein the morphology of the curve may be used to identify a therapeutically effective dose of a treatment.

[0127] In some embodiments, a marker of the present disclosure can be displayed as a curve generated according the methods described herein, wherein the morphology of the curve can be tracked in a spatiotemporal manner, and wherein the change to the morphology of the curve may be used to deduce the pharmacokinetics of a drug, and subsequently provide information as to whether a treatment dose should be increased or decreased.

[0128] In some embodiments, the present disclosure provides methods of identifying one or more markers via generating a curve that is reflective of a disease and / or injury (e.g., an enteropathy) along the entirety of the small bowel, and / or one or more regions of interest therein.

[0129] In some embodiments, a curve can be generated by determining an injury score at one or more points along the length of the small bowel, wherein the injury score comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; andwherein 3 is complete villous atrophy; and then generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof, e.g., by calculating: a curve fit to the injury score described above for the entirety of the small bowel of the subject, and using equally spaced points therein; and a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof.

[0130] Similarly, in some embodiments, a curve can be generated by determining an injury score at one or more points along the length of the small bowel; and then generating a summary score for the entire small bowel of a subject and / or one or more regions of interest (ROI) therein, e.g., by calculating: a curve fit to the injury score described above for the entirety of the small bowel of the subject, and using equally spaced points therein; and a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof, wherein the injury score can be determined using one or more of the following methods, without limitation: the level intensity of villous atrophy as determined using video capsule endoscopy (VCE) frame capture; villous height / crypt depth (Vh:Cd) ratio; serology, e.g., Elispot, IL-2, and other analytes; IEL count; Marsh score; patient- reported outcomes; differential or altered gene expression that can be detected by changes in the detectable amount of gene expression (such as cDNA or mRNA), or by changes in the detectable amount of proteins expressed by those genes.

[0131] In some embodiments, a marker (e.g., the morphology of a curve generated according the methods described herein) may be identified in a subject suffering from a disease state or condition, wherein the morphology of the curve is indicative of said disease state or condition.

[0132] For example, in some embodiments, a marker (e.g., the morphology of a curve generated according the methods described herein) in a subject (or a population of subjects) afflicted with a disease or condition can be compared relative to a marker (e.g., the morphology of a curve) in a healthy or normal subject (or a population of healthy or normal subjects). Here, the differential morphology of the curves (e.g., shape of the curves) in the respective markers indicates quantitative, as well as qualitative, differences in the distribution of the disease.

[0133] In some embodiments, comparing two or more markers is useful in a variety of different applications in diagnostic, sub-typing, therapeutic, drug development and relatedareas. Here, the marker may be generated as a curve, wherein the morphology of a curve generated according the methods described herein can be indicative of a disease state or condition, disease subtype, and / or stage in the disease state’s progression.

[0134] In other embodiments, the differential morphologies of one or more markers can be used as a point of reference to compare and characterize unknown samples and samples for which further information is sought.

[0135] As described above, a marker of the present disclosure, identifiable pursuant to the methods described herein, can be a summary of damage (as determined, e.g., based on the level or intensity of injury, such as villous atrophy) along the entire small bowel of a subject and / or one or more regions of interest (ROI) therein; wherein the summary of damage is reflected in a curve, the morphology of which (e.g., shape, slope, etc.) produces a signature indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0136] In some embodiments, a marker of the present disclosure can be a “diagnostic biomarker” wherein the diagnostic biomarker detects or confirms presence of a disease or condition, e.g., to inform a decision of procedural intervention vs. no treatment, or a decision of whether a therapeutic approach may be considered. The latter requires elucidation of what biological processes are dysregulated but may not require whether the condition is causally related to the dysregulation.

[0137] In some embodiments, a marker of the present disclosure can be a “prognostic biomarker,” wherein the prognostic biomarker is used to stratify individual patient risk of an adverse event in the future; in some embodiments, a prognostic biomarker requires a formalism that captures not only diagnostic differences between individuals but those differences that are of a magnitude to yield different expected outcomes.

[0138] In some embodiments, a marker of the present disclosure can be a “monitoring biomarker,” wherein the monitoring biomarker is a serial assessment of diagnostic biomarker. This requires that the assessment be a ratio or interval variable, i.e., not just a “score”, because quantitative comparisons are made across points in time. Such a biomarker builds on a prognostic biomarker in terms of the needed mathematical form but with a sensitivity that can not only measure inter-individual differences but in fact intra-individual (which is generally more demanding than inter-individual).

[0139] In some embodiments, a marker of the present disclosure can be a “pharmacodynamic / response biomarker” wherein the pharmacodynamic / response biomarker measures current response after receiving a specific therapeutic. In some embodiments, pharmacodynamic / response biomarkers build on monitoring biomarkers, but generally require a model of causation to be able to determine whether the change was due to the specific therapeutic vs. some other reason. Depending on the drug being tested, several parameters can be used as a pharmacodynamic / response biomarker.

[0140] In some embodiments, a marker of the present disclosure can be a “predictive biomarker” wherein the predictive biomarker is used to identify likely future response to a specific therapeutic, generally incorporating a pharmacodynamic model by providing a means to run it out into future cycles from a set of initial conditions.

[0141] In some embodiments, a marker of the present disclosure can be a “reasonably likely surrogate endpoint” wherein the reasonably likely surrogate endpoint is an endpoint supported by a strong mechanistic and / or epidemiologic rationale demonstrated to capture a high fraction of treatment effect. In some embodiments, reasonably likely surrogate endpoints build on a pharmacokinetic model with conclusive evidence that bias and confounding are not limiting generalizability to previously unseen patients of documented characteristics. Surrogate endpoints may be used instead of clinical outcomes in some clinical trials.

[0142] In some embodiments, a marker of the present disclosure can be a “safety biomarker” and / or a “susceptibility / risk biomarker” types, that identify current actual toxicity or likely future negative reaction, and are counterparts to diagnostic and prognostic markers but where the focus is on off-target effects that occur relative to the intended target but for which assessment is required.

[0143] In some embodiments, a marker of the present disclosure may be indicative of an enteropathy, or a lack thereof, in a subject.

[0144] In some embodiments, a marker of the present disclosure may be indicative of a level of severity of an enteropathy in a subject.

[0145] In some embodiments, a marker of the present disclosure may be indicative of a likely therapeutic response to a treatment for an enteropathy in a subject.

[0146] In some embodiments, a marker of the present disclosure may be indicative of a likely adverse response to a treatment for an enteropathy in a subject.

[0147] In some embodiments, a marker of the present disclosure may be indicative of an actual therapeutic response to a treatment for an enteropathy in a subject.

[0148] In some embodiments, a marker of the present disclosure may be indicative of an actual adverse response to a treatment for an enteropathy in a subject.

[0149] In some embodiments, a marker of the present disclosure may be indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0150] Methods of determining an injury score (from which a summary score can be generated in order to identify one or more markers) are described herein, and can include methods known in the art, e.g., and without limitation: a visual assessment of villous atrophy, e.g., a visual analysis of one or more image frames (e.g., one or more photographic image frames; one or more sonographic image frames; one or more radiographic image frames; one or more confocal image frames; or one or more tomographic image frames; e.g., one or more frames of a video as obtained via video capsule endoscopy (VCE) frame capture), and the subsequent analysis of the degree or amount of villous atrophy present in the one or more image frames; calculating villous height / crypt depth (Vh:Cd) ratio; performing serology analyses, e.g., Elispot, IL-2, and other analytes; performing IEL counts; calculating a Marsh score; recording patient-reported outcomes; and detecting differential or altered gene expression are known in the art. Accordingly, determining an injury score comprising a level of injury intensity along the entirety of the small bowel and / or one or more ROI therein, and the respective levels thereof, can be accomplished a variety of ways that are known to those having ordinary skill in the art. For example, methods may include calculating villous height / crypt depth (Vh:Cd) ratio; performing serology analyses, e.g., Elispot, IL-2, and other analytes; performing IEL counts; calculating a Marsh score; recording patient-reported outcomes; detecting altered gene expression, epigenetic modifications, germ-line or somatic mutations, etc. ; detecting the presence, quantity, or change in quantity, of an mRNA relative to a control; detecting the level of a metabolite reflective of a gene’s expression or activity. In some embodiments, the term “decreased level” as used herein, refers to a decrease in the abundance level of one or more indicators of injury score of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or more, or a decrease of greater than 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 50-fold, 100- fold or more as measured by one or more methods described herein. In some embodiments, the term “increased level” as used herein, refers to an increase in the abundance one or more indicators of injury score of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or more, or an increase of greaterthan 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 50-fold, 100-fold or more as measured by one or more methods, such as method described herein.

[0151] Additional methods identifying and comparing markers, e.g., identifying one or more markers in the small bowel of a subject; diagnosing an enteropathy in the subject; determining a level of severity of an enteropathy in the subject; identifying a biological response to one or more treatments for an enteropathy in the subject; or identifying one or more treatments for an enteropathy in the subject; are described below.

[0152] Enteropathies: Generally

[0153] As used herein, the term “enteropathy” refers to a disease of, and / or injury to, the small bowel, and / or one or more regions of interest (ROI) therein. For example, in some embodiments, the term “enteropathy” can refer to a disease of, and / or injury to, the entirety of small bowel of the subject. In other embodiments, the term “enteropathy” can refer to a disease of, and / or injury to, one or more regions of interest (ROI) of the small bowel of the subject. In yet other embodiments, the term “enteropathy” can refer to a disease of, and / or injury to, the entirety of small bowel of the subject and one or more regions of interest (ROI) of the small bowel of the subject.

[0154] In some embodiments, an enteropathy can refer to a disease of the small bowel.

[0155] In some embodiments, an enteropathy can refer to an injury to the small bowel.

[0156] In some embodiments, an enteropathy can refer to a disease of the small bowel, and an injury to the small bowel (e.g., in a patient having CeD, and further having an ulcer in one or more ROI).

[0157] In some embodiments, an enteropathy can refer to a disease affecting the entirety of the small bowel.

[0158] In some embodiments, an enteropathy can refer to one or more diseases affecting the entirety of the small bowel.

[0159] In some embodiments, an enteropathy can refer to an injury affecting the entirety of the small bowel.

[0160] In some embodiments, an enteropathy can refer to one or more injuries affecting the entirety of the small bowel.

[0161] In some embodiments, an enteropathy can refer to a disease affecting one or more ROI of the small bowel.

[0162] In some embodiments, an enteropathy can refer to one or more diseases affecting one or more ROI of the small bowel.

[0163] In some embodiments, an enteropathy can refer to one or more injuries affecting one or more ROI of the small bowel.

[0164] In some embodiments, an enteropathy can refer to a combination of one or more diseases, and / or one or more injuries, wherein said one or more diseases and / or one or more injuries affect the entirety of the small bowel, one or more ROI therein, and / or a combination thereof. For example, in some embodiments, an enteropathy can refer to a disease and / or one or more injuries at one or more loci over the entirety of the small bowel.

[0165] Accordingly, in some embodiments, an enteropathy of the present disclosure can be a disease of, or injury to: (1) the entirety of the small bowel; (2) one or more regions of interest (ROI) of the small bowel; or (3) a combination thereof.

[0166] In some embodiments, an enteropathy of the present disclosure can be: celiac disease (CeD); adenocarcinoma; amyloidosis; antibiotic associated diarrhea; arteriovenous malformations; bleeding ulcers; cancer; chronic granulomatous disease; collagenous colitis; colitis associated with radiotherapy or chemotherapy; colitis associated with disorders of innate immunity as in leukocyte adhesion deficiency-1; Crohn’s disease (e.g., active Crohn's disease, refractory Crohn's disease, or fistulizing Crohn's disease); diversion colitis; diverticulitis; drug-induced enteropathy; drug or chemical-induced colitis; dysbiotic enteropathy; dysmotility; dyspepsia; eosinophilic gastroenteritis; enteropathy associated with seronegative arthropathies; familial polyposis; food allergies; functional gastrointestinal disorders; gastric hyperacidity; gastritis; gastroesophageal reflux disease; gastrointestinal inflammation caused by an infectious agent; gastroparesis; gluten disorders; hemolytic- uremic syndrome colitis; hemorrhagic colitis; indeterminate colitis; infection; infectious colitis; infectious gastritis or enterocolitis (e.g., Helicobacter y / rnv- infected chronic active gastritis); inflammation; inflammatory bowel disease (IBD); intestinal lymphangiectasia; intestinal lymphoma; intestinal obstruction; iron deficiency anemia; irritable bowel syndrome; ischemic colitis; lactose intolerance; malabsorption; microscopic colitis; nonsteroidal anti-inflammatory drugs (NSAID) enteropathy; non-celiac gluten sensitivity (NCGS); nontropical Sprue; obscure bleeding; peptic ulcers; Peutz-Jeghers syndrome; pouchitis; protein-losing enteropathy; pseudo-obstruction; pseudomembranous colitis; regional enteritis; short-bowel (anastomosis) syndrome; small intestinal bacterial overgrowth; stress ulcers; ulcers; ulcerative colitis; Whipple’s disease; or Zollinger-Ellison syndrome.

[0167] In some embodiments, a symptom of an enteropathy of the present disclosure can be one or more of the following: abdominal bloating; abdominal distension; abdominal pain; anemia; anxiety; bloating; blood in stool or vomit; bruising easily; constipation; defects in tooth enamel; delayed puberty; dental enamel hypoplasia; depression; dermatitis; dermatitis herpetiformis; diarrhea (recurrent); diarrhea (chronic); excessive gas; fatigue; folate or vitamin B12 deficiency; gas; growth delay in children; hair loss; hemorrhage; idiopathic peripheral neuropathy; increased intraepithelial lymphocytes with crypt hyperplasia; indigestion; iron deficiency anemia; ischemia; joint pain; low birthweight offspring; malabsorption; metabolic bone disease; missed menstrual periods; mouth ulcers; muscle cramps; nausea; neurological symptoms, e.g., ataxia or paresthesia; nonhereditary cerebellar ataxia; nosebleeds; pain; persistent aphthous stomatitis; persistent elevation in serum aminotransferases; premature osteoporosis; recurrent headaches; recurrent fetal loss; reduced fertility; seizures; sudden and / or unexpected weight loss; swollen, painful belly; tingling or numbness in hands or feet; weight loss; mild, moderate or severe villus atrophy with crypt hyperplasia; or vomiting.

[0168] In some embodiments, a symptom of an enteropathy of the present disclosure (e.g., celiac disease) can be one or more of the following: abdominal pain; bloating; diarrhea; fatigue; weight loss; excessive gas; indigestion; constipation; delayed puberty; defects in tooth enamel; abdominal distension; nausea and / or vomiting; anemia; bruising easily; depression; anxiety; growth delay in children; hair loss; dermatitis; missed menstrual periods; mouth ulcers; muscle cramps; joint pain; nosebleeds; seizures; tingling or numbness in hands or feet; and / or neurological symptoms (e.g., ataxia or paresthesia).

[0169] In some embodiments, an enteropathy of the present disclosure can be celiac disease (CeD).

[0170] Celiac disease (CeD)

[0171] Celiac disease (also known as celiac sprue or gluten intolerance) is a highly prevalent disease in which dietary proteins found in wheat, barley, and rye products known as “glutens” evoke an immune response in the small intestine of genetically predisposed individuals. The resulting inflammation can lead to the degradation of the villi of the small intestine, impeding the absorption of nutrients.

[0172] Symptoms of CeD can appear in early childhood or later in life, and range widely in severity. For example, symptoms of CeD include, but are not limited to: abdominal pain; bloating; diarrhea; fatigue; weight loss; excessive gas; indigestion; constipation; delayed puberty; defects in tooth enamel; abdominal distension; nausea and / or vomiting;anemia; bruising easily; depression; anxiety; growth delay in children; hair loss; dermatitis; missed menstrual periods; mouth ulcers; muscle cramps; joint pain; nosebleeds; seizures; tingling or numbness in hands or feet; and / or neurological symptoms (e.g., ataxia or paresthesia).

[0173] Celiac disease is a disease of the entire small bowel, yet present methods to measure villous injury are primarily restricted to the duodenum. A significant portion of the celiac disease population may experience minor or no symptoms though they have evidence of damaged villi. Invasive duodenal biopsy is well recognized as having technical limitations for celiac disease (CeD) evaluation; although quick to perform, it presents some risk because it is often performed under sedation, with small risk of bleeding or perforation. Results depend on the biopsy’s orientation and the pathologist’s expertise, capture a limited sample of the proximal intestine (typically <100 villi), and do not reveal whether disease extends beyond the duodenum (approximately two-thirds of patients have disease involvement that is not limited to the duodenum). Furthermore, it is common practice to take biopsy samples where there is apparent villous damage which further reduces the ability of biopsy to represent change in the total burden of the disease. Additionally, some patients may not be able to undergo the procedure safely because of cardiopulmonary disease and bleeding disorders.

[0174] When pathological changes are observed, experts disagree in their assessments of disease severity as seen in duodenal pathology in CeD. Examination of interobserver agreement between pathologists found that the levels of agreement between observers varied based on the scoring method used, limiting reproducibility and longitudinal comparability. The highest agreement was observed with dichotomous evaluation for the presence or absence of villous atrophy (K = 0.84), but lower interobserver agreement was reported when nonbinary scales may, in one example embodiment, be used for evaluation by Corazza- Villanacci classification (K = 0.39) and the Marsh-Oberhuber system (K = 0.31).

[0175] In some embodiments, the methods of the present disclosure can be used to identify one or more markers of CeD in the small bowel of a subject having of CeD; diagnose of CeD in a subject; determine a level of severity of CeD in a subject; identify a biological response to one or more treatments for CeD in a subject; or identify one or more treatments for of CeD in the subject.

[0176] Detailed descriptions of these methods are provided below.

[0177] METHODS OF USE

[0178] Identifying markers

[0179] The present disclosure describes methods of identifying one or more markers in the small bowel of a subject, wherein the one or more markers of the present disclosure may be indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0180] In some embodiments, a method of the present disclosure comprises identifying one or more markers in the entire small bowel of a subject, or one or more regions of interest (ROI) therein.

[0181] In some embodiments, a method of the present disclosure comprises identifying one or more markers in the entire small bowel of a subject.

[0182] In some embodiments, a method of the present disclosure comprises identifying one or more markers in one or more ROI of the small bowel of a subject.

[0183] In some embodiments, a method of the present disclosure comprises identifying one or more markers in the entire small bowel of a subject, or one or more ROI therein, wherein the subject is confirmed as not having an enteropathy. For example, in some embodiments, a subject confirmed as not having an enteropathy may serve as a reference subject, wherein the one or more markers identified in the reference subject may be compared to one or more markers in the entire small bowel of a subject, or one or more ROI therein, of a test subject diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy.

[0184] In some embodiments, a method of the present disclosure comprises identifying one or more markers in the entire small bowels of a plurality of subjects, or one or more ROI therein, wherein the plurality of subjects are each independently confirmed as not having an enteropathy. For example, in some embodiments, a plurality of subjects confirmed as not having an enteropathy may serve a plurality of reference subjects, and / or a plurality of reference markers, wherein the one or more markers identified in the plurality of reference subjects may be compared to one or more markers in the entire small bowels of a plurality of test subjects, or one or more ROI therein, wherein the test subject diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy.

[0185] In some embodiments, the markers of the present disclosure can be identified spatially and / or temporally. For example, in some embodiments, one or more reference markers can be compared to one or more subject markers, in order to determine the change in severity of an enteropathy over time, and at one or more locations in the small bowel.

[0186] In some embodiments, one or more markers can be identified prior to treating or having treated the subject with a treatment for the enteropathy.

[0187] In some embodiments, one or more markers can be identified during the treatment of the subject for the enteropathy.

[0188] In some embodiments, one or more markers can be identified after treating the subject with the treatment for the enteropathy.

[0189] In some embodiments, one or more markers can be identified during at least two time points, wherein the two time points are selected from: one or more time points prior to the treatment of the subject, one or more time points during the treatment of the subject, or one or more time points after the treatment of the subject, for the enteropathy.

[0190] In some embodiments, one or more markers can be identified to establish one or more reference markers indicative of an enteropathy, or a lack thereof, in a subject diagnosed with or confirmed to have the enteropathy.

[0191] In some embodiments, a method of identifying one or more markers in the small bowel of a subject comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof.

[0192] In some embodiments, a method of identifying one or more markers in the small bowel of a subject comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more indicators of small bowel injury are: a villous height / crypt depth (Vh:Cd) ratio; an enzyme-linked immunosorbent spot (ELISpot) assay; an IL-2 serologyassay; a CD4 assay; a CD8 assay; an intraepithelial lymphocytes (IEL) count; a Marsh score; a patient-reported outcome assessment; or villous atrophy.

[0193] In some embodiments, a method of identifying one or more markers in the small bowel of a subject comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more indicators of small bowel injury are villous atrophy.

[0194] In some embodiments, a method of identifying one or more markers in the small bowel of a subject comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more indicators of small bowel injury are villous atrophy as determined via a visual assessment of one or more image frames; and wherein the one or more image frames are one or more photographic image frames; one or more sonographic image frames; one or more radiographic image frames; one or more confocal image frames; or one or more tomographic image frames.

[0195] In some embodiments, a method of identifying one or more markers in the small bowel of a subject comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or moreregions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more indicators of small bowel injury are villous atrophy as determined via a visual assessment of one or more image frames; and wherein the one or more image frames are one or more photographic image frames.

[0196] In some embodiments, a method of identifying one or more markers in the small bowel of a subject comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more indicators of small bowel injury are one or more photographic image frames; and wherein the one or more photographic image frames are one or more frames of a video.

[0197] In some embodiments, a method of identifying one or more markers in the small bowel of a subject comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the ordinal scale comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy.

[0198] In some embodiments, a method of identifying one or more markers in the small bowel of a subject comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summaryscore generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the ordinal scale comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy; and wherein the one or more indicators of small bowel injury are one or more frames of a video.

[0199] In some embodiments, a method of identifying one or more markers in the small bowel of a subject comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more indicators of small bowel injury are one or more frames of a video; wherein the ordinal scale comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy; and wherein the injury score is determined for each of the one or more frames of the video.

[0200] In some embodiments, a method of identifying one or more markers in the small bowel of a subject comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more indicators of small bowel injury are one or more frames of a video; wherein the ordinal scale comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy; and wherein the injury score is determined for each of the one or more frames of the video; and further comprising generating a summary score for: the entire small bowel of the subject, one or more regions of interest (ROI) of the small bowel of the subject, or a combination thereof; wherein the summary score is generated by calculating: (a) a curve fit to the injury score for each of theone or more frames of the video, for the entirety of the small bowel of the subject, and using equally spaced points therein; and (b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof.

[0201] In some embodiments, a method of identifying one or more markers in the small bowel of a subject comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more markers are indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0202] In some embodiments, a method of identifying one or more markers in the small bowel of a subject comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more markers are identified for: (a) the entire small bowel of: (i) a subject confirmed as not having an enteropathy; (ii) a plurality of subjects, wherein each subject of the plurality of subjects are independently confirmed as not having an enteropathy; (iii) a subject diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy; (iv) a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy; or (b) one or more regions of interest (ROI), comprising: (i) one or more ROI of the small bowel of a subject, wherein the subject isconfirmed as not having an enteropathy in the one or more ROI; (ii) a plurality of one or more ROI of the small bowels of a plurality of subjects, wherein each subject of the plurality of subjects are independently confirmed as not having an enteropathy in the one or more ROIs; (iii) one or more ROI of the small bowel of a subject, wherein the subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy in the one or more ROI; (iv) a plurality of one or more ROI of the small bowels of a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy in the one or more ROI.

[0203] In some embodiments, a method of identifying one or more markers in the small bowel of a subject comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more markers are identified: (a) prior to treating or having treated the subject with a treatment for the enteropathy; (b) during the treatment of the subject for the enteropathy; (c) after treating the subject with the treatment for the enteropathy; (d) during at least two time points, wherein the two time points are selected from: one or more time points prior to the treatment of the subject, one or more time points during the treatment of the subject, or one or more time points after the treatment of the subject, for the enteropathy; or (e) to establish one or more reference markers indicative of an enteropathy, or a lack thereof, in a subject diagnosed with or confirmed to have the enteropathy.

[0204] Diagnosing or identifying an enteropathy

[0205] In some embodiments, a method of the present disclosure comprises identifying one or more markers in the entire small bowel of a subject, or one or more regions of interest (ROI) therein, and further comprises a method of diagnosing or identifying an enteropathy in the subject.

[0206] For example, in some embodiments, a method of the present disclosure comprises diagnosing or identifying an enteropathy in a subject, the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers compriseat least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, or a combination thereof; and (2) comparing the at least two or more markers.

[0207] In some embodiments, a method of the present disclosure comprises diagnosing or identifying an enteropathy in a subject, the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, or a combination thereof; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of a first reference subject, wherein the first reference subject is confirmed as not having the enteropathy; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is confirmed as not having the enteropathy in the one or more first reference ROI; or (iii) a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of a second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy in the one or more second reference ROI; or (iii) a combination thereof; and (c) wherein the one or more subject markers comprise the summary score for: (i) the entire small bowel of the subject; (ii) one or more subject ROI of the small bowel of the subject; or (iii) a combination thereof; and (2) comparing the at least two or more markers; wherein: (i) if the one or more subject marker summary scores are comparable to the one or more first reference markers summary score, then the subject is diagnosed as not having the enteropathy; (ii) if the one or more subject marker summary scores are comparable to the one or more second reference markers summary score, then the subject is diagnosed as having the enteropathy.

[0208] In some embodiments, a method of the present disclosure comprises identifying one or more markers in the small bowel of a subject, the method comprising: (1) capturing one or more frames of a video of the small bowel of the subject; (2) determining an injury score for each of the one or more frames of the video, wherein the injury score comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject;or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof.

[0209] In some embodiments, the one or more markers identified according to the methods of the present disclosure are indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0210] For example, in some embodiments, the one or more markers identified according to the methods of the present disclosure are indicative of an enteropathy, wherein the enteropathy can be diagnosed and / or identified using a known standard, e.g., one or more markers from a reference subject diagnosed with, and / or confirmed to have, the enteropathy.

[0211] In some embodiments, diagnosing or identifying an enteropathy in a subject comprises comparing at least two or more markers, e.g., one or more subject markers obtained from the subject, and comparing those one or more subject markers to one or more first reference markers (e.g., taken from a first reference subject diagnosed with, and / or confirmed to have, the enteropathy) and / or one or more second reference markers (e.g., taken from a second reference subject diagnosed with, and / or confirmed to have, the enteropathy).

[0212] In some embodiments, diagnosing or identifying an enteropathy in a subject comprises comparing at least two or more markers, e.g., one or more subject markers obtained from the subject, and comparing those one or more subject markers to one or more first reference markers (e.g., taken from a first reference subject diagnosed with, and / or confirmed to have, the enteropathy) and / or one or more second reference markers (e.g., taken from a second reference subject confirmed as not having an enteropathy).

[0213] In some embodiments, the second reference subject can either be a subject that has been diagnosed with, and / or confirmed to have, the enteropathy; or the second reference subject can be a subject that has been successfully treated with one or more treatments, thus providing the user with reference markers with which to evaluate a therapeutic response.

[0214] In some embodiments, the second reference subject can either be a subject that has been diagnosed with, and / or confirmed to have, the enteropathy; or the second reference subject can be a subject that has been successfully treated with one or more treatments, thus providing the user with reference markers with which to evaluate a therapeutic response.

[0215] For example, in some embodiments, a method of diagnosing or identifying an enteropathy in a subject comprises comparing at least two or more markers, e.g., one or more subject markers obtained from the subject to be evaluated, and comparing those one or more subject markers to one or more first reference markers (e.g., taken from a first reference subject diagnosed with, and / or confirmed to have, the enteropathy) and / or one or more second reference markers (e.g., taken from a second reference subject who has subject who is confirmed as not having an enteropathy), wherein: (i) if the one or more subject marker summary scores are comparable to the one or more first reference markers summary score, then the subject is diagnosed as not having the enteropathy; or (ii) if the one or more subject marker summary scores are comparable to the one or more second reference markers summary score, then the subject is diagnosed as having the enteropathy.

[0216] In yet other embodiments, a method of diagnosing or identifying an enteropathy in a subject comprises comparing at least two or more markers, e.g., one or more subject markers obtained from the subject to be evaluated, and comparing those one or more subject markers to one or more first reference markers (e.g., taken from a first reference subject diagnosed with, and / or confirmed to have, the enteropathy) and / or one or more second reference markers (e.g., taken from a second reference subject who has had an actual therapeutic response), wherein: (i) if the one or more subject marker summary scores are comparable to the one or more first reference markers summary score, then the subject is diagnosed as not having the enteropathy; or (ii) if the one or more subject marker summary scores are comparable to the one or more second reference markers summary score, then the subject is diagnosed as having an actual therapeutic response.

[0217] Determining a level of severity of an enteropathy

[0218] In some embodiments, a method of the present disclosure comprises identifying one or more markers in the entire small bowel of a subject, or one or more regions of interest (ROI) therein, and further comprises a method of determining a level of severity of an enteropathy.

[0219] In some embodiments, a method of determining a level of severity of an enteropathy comprises: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, or a combination thereof; and (2) comparing the at least two or more markers.

[0220] In some embodiments, a method of determining a level of severity of an enteropathy comprises: (1) identifying at least two or more markers, wherein the at least twoor more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, or a combination thereof; and (2) comparing the at least two or more markers; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of a first reference subject, wherein the first reference subject is confirmed as not having the enteropathy; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is confirmed as not having the enteropathy in the one or more first reference ROI; or (iii) a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of a second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy in the one or more second reference ROI; or (iii) a combination thereof; and (c) wherein the one or more subject markers comprise the summary score for: (i) the entire small bowel of the subject; (ii) one or more subject ROI of the small bowel of the subject; or (iii) a combination thereof.

[0221] In some embodiments, a method of determining a level of severity of an enteropathy comprises: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, or a combination thereof; and (2) comparing the at least two or more markers; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of a first reference subject, wherein the first reference subject is confirmed as not having the enteropathy; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is confirmed as not having the enteropathy in the one or more first reference ROI; or (iii) a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of a second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy in the one or more second reference ROI; or (iii) a combination thereof; and (c) wherein the one or more subject markerscomprise the summary score for: (i) the entire small bowel of the subject; (ii) one or more subject ROI of the small bowel of the subject; or (iii) a combination thereof; and wherein if the one or more subject marker summary scores are comparable to or less than the one or more first reference markers summary scores, then the subject is determined to have a less severe enteropathy, relative to the level of severity of the enteropathy in the first reference subject; or if the one or more subject marker summary scores are comparable to or greater than the one or more second reference markers summary scores, then the subject is diagnosed as having a more severe enteropathy relative to the level of severity of the enteropathy in the second reference subject.

[0222] Identifying a biological response

[0223] In some embodiments, a method of the present disclosure comprises identifying one or more markers in the entire small bowel of a subject, or one or more regions of interest (ROI) therein (as described in the sections above), and further comprises a method of identifying a biological response to one or more treatments for an enteropathy in the subject.

[0224] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; wherein the biological response is a likely therapeutic response to the one or more treatments for the enteropathy.

[0225] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; wherein the biological response is a likely adverse response to the one or more treatments for the enteropathy.

[0226] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; wherein the biological response is an actual therapeutic response to the one or more treatments for the enteropathy.

[0227] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; wherein the biological response is an actual adverse response to the one or more treatments for the enteropathy.

[0228] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; wherein the biological response is an improvement to a level of severity, or lack thereof, ofthe enteropathy; wherein the improvement or lack thereof is determined spatially, temporally, or a combination thereof.

[0229] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; and (2) comparing the at least two or more markers.

[0230] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; and (2) comparing the at least two or more markers; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of a first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, wherein the first reference subject has an actual therapeutic response to the one or more treatments in the entire small bowel; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the one or more treatments in the one or more first ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof.

[0231] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; and (2) comparing the at least two or more markers; (b) wherein the one or more second reference markers comprise thesummary score for: (i) the entire small bowel of a second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the second reference subject does not have an actual therapeutic response to the one or more treatments in the entire small bowel;(ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have enteropathy in the one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the one or more treatments in the one or more second ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof.

[0232] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; and (2) comparing the at least two or more markers; (c) wherein the one or more third reference markers comprise the summary score for: (i) the entire small bowel of a third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the one or more treatments in the entire small bowel; (ii) one or more third reference ROI of the small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the one or more treatments in the one or more third ROI; or(iii) a combination thereof; wherein the summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof.

[0233] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers as described herein, e.g., determining an injury score comprising a level of injury intensity, and generating a summary score for the entire small bowel of the subject and / or one or more regions of interest (ROI)therein by calculating a curve fit to the injury score the entirety of the small bowel of the subject, and using equally spaced points therein; and a mean injury score; and a maximum point along the curve, for the entirety of the small bowel and / or one or more regions of interest (ROI) therein; wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; and (2) comparing the at least two or more markers.

[0234] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers as described herein, e.g., determining an injury score comprising a level of injury intensity, and generating one or more summary scores for the entire small bowel of each of one or more subjects and / or their respective one or more regions of interest (ROI) therein, by calculating a curve fit to the injury score the entirety of the small bowel of each of the one or more subjects, and using equally spaced points therein; and a mean injury score; and a maximum point along the curve, for the entirety of each of the small bowels and / or one or more regions of interest (ROI) therein; wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; and (2) comparing the at least two or more markers; wherein(a) the one or more first reference markers comprise a first summary score for the entire small bowel of a first reference subject and / or one or more first reference ROI therein, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and has an actual therapeutic response to the one or more treatments; and wherein the first summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof;(b) the one or more second reference markers comprise a second summary score for the entire small bowel of a second reference subject and / or one or more second reference ROI therein, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and does not have an actual therapeutic response to the one or more treatments; and wherein the second summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof;(c) the one or more third reference markers comprise a third summary score for the entire small bowel of a third reference subject and / or one or more third reference ROI therein, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and has an actual adverse response to the one or more treatments; wherein the third summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and(d) the one or more subject markers comprise a subject summary score for the entire small bowel of the subject and / or one or more subject ROI therein, wherein the subject summary score is determined prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (2) comparing the at least two or more markers.

[0235] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers as described herein, e.g., determining an injury score comprising a level of injury intensity, and generating one or more summary scores for the entire small bowel of each of one or more subjects and / or their respective one or more regions of interest (ROI) therein, by calculating a curve fit to the injury score the entirety of the small bowel of each of the one or more subjects, and using equally spaced points therein; and a mean injury score; and a maximum point along the curve, for the entirety of each of the small bowels and / or one or more regions of interest (ROI) therein; wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; and (2) comparing the at least two or more markers; wherein (a) the one or more first reference markers comprise a first summary score for the entire small bowel of a first reference subject and / or one or more first reference ROI therein, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and has an actual therapeutic response to the one or more treatments; and wherein the first summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; (b) the one or more second reference markers comprise a second summary score for the entire small bowel of a second reference subject and / or one or more second reference ROI therein, wherein the second reference subject is diagnosed with, is suspected of having, is displayingsymptoms of, or is confirmed to have the enteropathy, and does not have an actual therapeutic response to the one or more treatments; and wherein the second summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; (c) the one or more third reference markers comprise a third summary score for the entire small bowel of a third reference subject and / or one or more third reference ROI therein, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and has an actual adverse response to the one or more treatments; wherein the third summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (d) the one or more subject markers comprise a subject summary score for the entire small bowel of the subject and / or one or more subject ROI therein, wherein the subject summary score is determined prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (2) comparing the at least two or more markers.

[0236] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of a first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the first reference subject has an actual therapeutic response to the one or more treatments in the entire small bowel; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the one or more treatments in the one or more first ROI; or (iii) a combination thereof; and (2) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined prior to the one or more treatments are comparable to the one or more first reference marker summary scores of any one of (l)(a)(i)-(iii) determined prior tothe one or more treatments, then the subject is identified as being likely to have an actual therapeutic response to the one or more treatments.

[0237] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of a first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the first reference subject has an actual therapeutic response to the one or more treatments in the entire small bowel; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the one or more treatments in the one or more first ROI; or (iii) a combination thereof; and (2) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined during or after the one or more treatments are comparable to the one or more first reference marker summary scores of any one of (l)(a)(i)-(iii) determined during or after the one or more treatments, then the subject is identified as having an actual therapeutic response to the one or more treatments.

[0238] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of a second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the second reference subject does not have an actual therapeutic response to the one or more treatments in the entire small bowel; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject isdiagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have enteropathy in the one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the one or more treatments in the one or more second ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (2) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined prior to the one or more treatments are comparable to the one or more second reference marker summary scores of any one of ( 1 )(b)(i)-(iii) determined prior to the one or more treatments, then the subject is identified as being likely to not have an actual therapeutic response to the one or more treatments.

[0239] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of a second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the second reference subject does not have an actual therapeutic response to the one or more treatments in the entire small bowel; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have enteropathy in the one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the one or more treatments in the one or more second ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (2) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined during or after the one or more treatments are comparable to the one or more second reference marker summary scores of any one of (l)(b)(i)-(iii) determined during or after the one or more treatments, then the subject is identified as not having an actual therapeutic response to the one or more treatments.

[0240] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (c) wherein the one or more third reference markers comprise the summary score for: (i) the entire small bowel of a third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the one or more treatments in the entire small bowel; (ii) one or more third reference ROI of the small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the one or more treatments in the one or more third ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (2) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined prior to the one or more treatments are comparable to the one or more third reference marker summary scores of any one of ( 1 )(c)(i)-(iii) determined prior to the one or more treatments, then the subject is identified as being likely to have an actual adverse response to the one or more treatments.

[0241] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (c) wherein the one or more third reference markers comprise the summary score for: (i) the entire small bowel of a third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the one or more treatments in the entire small bowel; (ii) one or more third reference ROI of the small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, isdisplaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the one or more treatments in the one or more third ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (2) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined during or after the one or more treatments are comparable to the one or more third reference marker summary scores of any one of (l)(c)(i)-(iii) determined during or after the one or more treatments, then the subject is identified as having an actual adverse response to the one or more treatments.

[0242] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of a first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the first reference subject has an actual therapeutic response to the one or more treatments in the entire small bowel; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the one or more treatments in the one or more first ROI; or (iii) a combination thereof; and (2) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined prior and during the one or more treatments are comparable to either the: one or more first reference marker summary scores of any one of (l)(a)(i)-(iii), as determined prior and during the one or more treatments; then the subject is identified as having an actual therapeutic response to the one or more treatments over time.

[0243] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subjectmarkers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of a second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the second reference subject does not have an actual therapeutic response to the one or more treatments in the entire small bowel; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have enteropathy in the one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the one or more treatments in the one or more second ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (2) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined prior and during the one or more treatments are comparable to the one or more second reference marker summary scores of any one of (l)(b)(i)-(iii), as determined prior and during the one or more treatments; then the subject is identified as not having an actual therapeutic response to the one or more treatments over time.

[0244] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (c) wherein the one or more third reference markers comprise the summary score for: (i) the entire small bowel of a third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the one or more treatments in the entire small bowel; (ii) one or more third reference ROI of the small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the one or more treatments in the one or more third ROI; or (iii) a combination thereof; wherein thesummary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (2) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined prior and during the one or more treatments are comparable to the one or more third reference marker summary scores of any one of ( 1 )(c)(i)-(iii), as determined prior and during the one or more treatments; then the subject is identified as having actual adverse response to the one or more treatments over time.

[0245] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers as described herein, e.g., determining an injury score comprising a level of injury intensity, and generating one or more summary scores for the entire small bowel of each of one or more subjects and / or their respective one or more regions of interest (ROI) therein, by calculating a curve fit to the injury score the entirety of the small bowel of each of the one or more subjects, and using equally spaced points therein; and a mean injury score; and a maximum point along the curve, for the entirety of each of the small bowels and / or one or more regions of interest (ROI) therein; wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; and (2) comparing the at least two or more markers; wherein (a) the one or more first reference markers comprise a first summary score for the entire small bowel of a first reference subject and / or one or more first reference ROI therein, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and has an actual therapeutic response to the one or more treatments; and wherein the first summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; (b) the one or more second reference markers comprise a second summary score for the entire small bowel of a second reference subject and / or one or more second reference ROI therein, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and does not have an actual therapeutic response to the one or more treatments; and wherein the second summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; (c) the one or more third reference markers comprise a third summary score for the entire small bowel of a third reference subject and / orone or more third reference ROI therein, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and has an actual adverse response to the one or more treatments; wherein the third summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (d) the one or more subject markers comprise a subject summary score for the entire small bowel of the subject and / or one or more subject ROI therein, wherein the subject summary score is determined prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (2) comparing the at least two or more markers; wherein the one or more treatments comprise a single treatment.

[0246] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers as described herein, e.g., determining an injury score comprising a level of injury intensity, and generating one or more summary scores for the entire small bowel of each of one or more subjects and / or their respective one or more regions of interest (ROI) therein, by calculating a curve fit to the injury score the entirety of the small bowel of each of the one or more subjects, and using equally spaced points therein; and a mean injury score; and a maximum point along the curve, for the entirety of each of the small bowels and / or one or more regions of interest (ROI) therein; wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; and (2) comparing the at least two or more markers; wherein (a) the one or more first reference markers comprise a first summary score for the entire small bowel of a first reference subject and / or one or more first reference ROI therein, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and has an actual therapeutic response to the one or more treatments; and wherein the first summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; (b) the one or more second reference markers comprise a second summary score for the entire small bowel of a second reference subject and / or one or more second reference ROI therein, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and does not have an actual therapeutic response to the one or more treatments; and wherein the second summary score isdetermined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; (c) the one or more third reference markers comprise a third summary score for the entire small bowel of a third reference subject and / or one or more third reference ROI therein, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and has an actual adverse response to the one or more treatments; wherein the third summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (d) the one or more subject markers comprise a subject summary score for the entire small bowel of the subject and / or one or more subject ROI therein, wherein the subject summary score is determined prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (2) comparing the at least two or more markers; wherein the one or more treatments comprise two or more treatments.

[0247] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers as described herein, e.g., determining an injury score comprising a level of injury intensity, and generating one or more summary scores for the entire small bowel of each of one or more subjects and / or their respective one or more regions of interest (ROI) therein, by calculating a curve fit to the injury score the entirety of the small bowel of each of the one or more subjects, and using equally spaced points therein; and a mean injury score; and a maximum point along the curve, for the entirety of each of the small bowels and / or one or more regions of interest (ROI) therein; wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; and (2) comparing the at least two or more markers; wherein (a) the one or more first reference markers comprise a first summary score for the entire small bowel of a first reference subject and / or one or more first reference ROI therein, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and has an actual therapeutic response to the one or more treatments; and wherein the first summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; (b) the one or more second reference markers comprise a second summary score for the entire small bowel of a second reference subject and / or one or more second reference ROI therein,wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and does not have an actual therapeutic response to the one or more treatments; and wherein the second summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; (c) the one or more third reference markers comprise a third summary score for the entire small bowel of a third reference subject and / or one or more third reference ROI therein, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and has an actual adverse response to the one or more treatments; wherein the third summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (d) the one or more subject markers comprise a subject summary score for the entire small bowel of the subject and / or one or more subject ROI therein, wherein the subject summary score is determined prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (2) comparing the at least two or more markers; wherein the biological response is identified for each of the two or more treatments independently.

[0248] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; the method comprising: (1) identifying at least two or more markers as described herein, e.g., determining an injury score comprising a level of injury intensity, and generating one or more summary scores for the entire small bowel of each of one or more subjects and / or their respective one or more regions of interest (ROI) therein, by calculating a curve fit to the injury score the entirety of the small bowel of each of the one or more subjects, and using equally spaced points therein; and a mean injury score; and a maximum point along the curve, for the entirety of each of the small bowels and / or one or more regions of interest (ROI) therein; wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; and (2) comparing the at least two or more markers; wherein (a) the one or more first reference markers comprise a first summary score for the entire small bowel of a first reference subject and / or one or more first reference ROI therein, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and has an actual therapeutic response to the one or more treatments;and wherein the first summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; (b) the one or more second reference markers comprise a second summary score for the entire small bowel of a second reference subject and / or one or more second reference ROI therein, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and does not have an actual therapeutic response to the one or more treatments; and wherein the second summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; (c) the one or more third reference markers comprise a third summary score for the entire small bowel of a third reference subject and / or one or more third reference ROI therein, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy, and has an actual adverse response to the one or more treatments; wherein the third summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (d) the one or more subject markers comprise a subject summary score for the entire small bowel of the subject and / or one or more subject ROI therein, wherein the subject summary score is determined prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and (2) comparing the at least two or more markers; wherein the biological response is identified for each of the two or more treatments independently; and wherein the biological response is identified for each of the two or more treatments independently by comparing one or more markers between: a subject receiving a first of the two or more treatments, a subject receiving a second of the two or more treatments, or a subject receiving both of the two or more treatments.

[0249] In some embodiments, a method of the present disclosure comprises identifying a biological response to one or more treatments for an enteropathy in a subject; wherein the biological response is an improvement to a level of severity, or lack thereof, of the enteropathy; wherein the improvement or lack thereof is determined spatially, temporally, or a combination thereof; wherein the improvement to the level of severity, or lack thereof, is determined spatially by comparing at least two or more markers for: at least two or more different ROI in the same subject; or the same of one or more ROI obtained from two different subjects; wherein the improvement to the level of severity, or lack thereof, is determined temporally by comparing at least two or more markers for: the entire small bowel of the subject at a first time, and one or more subsequent times; or one or more regions ofinterest (ROI) of the small bowel of the subject at a first time, and one or more subsequent times.

[0250] Identifying a treatment for an enteropathy

[0251] In some embodiments, a method of the present disclosure comprises identifying one or more markers in the small bowel of a subject (as described above), wherein the one or more markers of the present disclosure may be indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy; and wherein the method further comprises identifying one or more treatments for the enteropathy, where applicable.

[0252] In some embodiments, a method of the present disclosure comprises identifying one or more markers in the entire small bowel of a subject, or one or more regions of interest (ROI) therein; determining a level of severity of an enteropathy; and / or identifying one or more treatments for the enteropathy.

[0253] In some embodiments, a method of the present disclosure comprises identifying one or more markers in the entire small bowel of a subject, or one or more regions of interest (ROI) therein; identifying a biological response to one or more treatments for an enteropathy in the subject; and / or identifying one or more treatments for the enteropathy.

[0254] For example, in some embodiments, any of the methods described herein may be used to identify one or more markers in the entire small bowel of a subject, or one or more regions of interest (ROI) therein (e.g., one or more markers indicative on an enteropathy), wherein said markers may be used to identify a suitable treatment for the enteropathy.

[0255] Accordingly, in some embodiments, a method of the present disclosure comprises (1) identifying one or more treatments, wherein the one or more treatments comprise at least one candidate treatment; (2) treating or having treated at least one or more of: a first reference subject, a second reference subject, and a third reference subject with the at least one candidate treatments; (3) identifying at least two or more markers; and (4) comparing the at least two or more markers, to identify one or more suitable treatments likely to provide an actual therapeutic response or an actual adverse response, in a spatiotemporal manner (e.g., over time during the course of treatment, and / or wherein the response can be determined for the entirety of the small bowel and / or one or more ROI therein).

[0256] In some embodiments, a method of the present disclosure comprises (1) identifying one or more treatments, wherein the one or more treatments comprise at least one candidate treatment; (2) treating or having treated at least one or more of: a first referencesubject, a second reference subject, and a third reference subject with the at least one candidate treatments; (3) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the one or more first ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the one or more second ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (c) wherein the one or more third reference markers comprise the summary score for: (i) the entire small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the entire small bowel; (ii) one or more third reference ROI of the small bowel of the thirdreference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the one or more third ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; and (d) wherein the one or more subject markers comprise the summary score for: (i) the entire small bowel of the subject; (ii) one or more subject ROI of the small bowel of the subject; or (iii) a combination thereof; and wherein the summary score is determined: prior to the at least one candidate treatment, or during the at least one candidate treatment; and (4) comparing the at least two or more markers.

[0257] In some embodiments, a method of the present disclosure comprises (1) identifying one or more treatments, wherein the one or more treatments comprise at least one candidate treatment; (2) treating or having treated at least one or more of: a first reference subject, a second reference subject, and a third reference subject with the at least one candidate treatments; (3) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the one or more first ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the secondreference subject does not have an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the one or more second ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (c) wherein the one or more third reference markers comprise the summary score for: (i) the entire small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the entire small bowel; (ii) one or more third reference ROI of the small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the one or more third ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; and (d) wherein the one or more subject markers comprise the summary score for: (i) the entire small bowel of the subject; (ii) one or more subject ROI of the small bowel of the subject; or (iii) a combination thereof; and wherein the summary score is determined: prior to the at least one candidate treatment, or during the at least one candidate treatment; and (4) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined prior to the at least one candidate treatment are comparable to the one or more first reference marker summary scores of any one of (a)(i)-(iii) determined prior to the at least one candidate treatment, then the at least one candidate treatment is identified as being likely to have an actual therapeutic response in the subject.

[0258] For example, in some embodiments, a method of the present disclosure comprises (1) identifying at least one candidate treatment for an enteropathy (e.g., celiac disease) in a subject in need thereof; (2) wherein the candidate treatment has been administered to the following reference subjects:• a first reference subject (e.g., a patient that is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have celiac disease; and who is an actual responder, i.e., demonstrates a therapeutic response to the candidate treatment);• a second reference subject (e.g., a patient that is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have celiac disease; but who is not a responder, i.e., the patient does not demonstrate a therapeutic response to the candidate treatment); and• a third reference subject (e.g., a patient that is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have celiac disease; and who has had an adverse reaction to the candidate treatment)

[0259] Next, markers will be identified in the subject, and in one or more reference subjects (e.g., a first, second, and / or third reference subject), wherein the markers comprise a summary score — e.g., as described herein, such as the summary of damage as determined, e.g., based on the level or intensity of villous atrophy and / or injury, along the entire small bowel of a subject and / or one or more regions of interest (ROI) therein. Thus, the subject, first reference subject, second reference subject, and third reference subject, will each have a respective marker comprising the summary score for the entire small bowel and / or one or more ROI therein, i.e., one or more subject markers; one or more first reference markers, one or more second reference markers, and one or more third reference markers.

[0260] In some embodiments, the one or more markers, e.g., the summary scores, are determined in each of the first, second, and / or third reference subjects prior to administration of the candidate treatment to each of the first, second, and / or third reference subjects. For example, in some embodiments, one or more first reference markers, one or more second reference markers, and / or one or more third reference markers, may be determined in the first reference subject, the second reference subject, and / or the third reference subject, all prior to being administered the candidate treatment.

[0261] In some embodiments, the one or more markers, e.g., the summary scores, are determined in each of the first, second, and / or third reference subjects during the administration of the candidate treatment to each of the first, second, and / or third reference subjects. For example, in some embodiments, one or more first reference markers, one or more second reference markers, and / or one or more third reference markers, may bedetermined in the first reference subject, the second reference subject, and / or the third reference subject, during the administration of the candidate treatment.

[0262] In other embodiments, the one or more markers, e.g., the summary scores, are determined in each of the first, second, and / or third reference subjects after the administration of the candidate treatment to each of the first, second, and / or third reference subjects. For example, in some embodiments, one or more first reference markers, one or more second reference markers, and / or one or more third reference markers, may be determined in the first reference subject, the second reference subject, and / or the third reference subject, after the administration of the candidate treatment.

[0263] In yet other embodiments, the one or more markers, e.g., the summary scores, can be determined in each of the first, second, and / or third reference subjects prior to, during, and / or after the administration of the candidate treatment to each of the first, second, and / or third reference subjects. For example, in some embodiments, one or more first reference markers, one or more second reference markers, and / or one or more third reference markers, may be determined in the first reference subject, the second reference subject, and / or the third reference subject, prior to, during, and / or after the administration of the candidate treatment.

[0264] Likewise, in some embodiments, the one or more subject markers, e.g., the subject’s summary score for the entire small bowel and / or one or more subject ROI therein, can be determined prior to administration with any putative treatment. In addition, in some embodiments, the subject markers can be evaluated pursuant to the methods described herein in order to determine responsiveness during, and / or after the administration of the candidate treatment.

[0265] In some embodiments, once the markers have been identified, they can be compared in order to identify a suitable treatment for the subject. For example, in some embodiments, the one or more subject markers can be compared to the one or more first reference markers, the one or more second reference markers, and / or the one or more third reference markers. Depending on the markers identified, upon performing this comparison, it can be determined whether the candidate treatment will result in a likely therapeutic response in the subject; an actual therapeutic response in the subject; an unlikely therapeutic response in the subject; a likely adverse response in the subject; or an actual adverse response in the subject.

[0266] For example, in some embodiments, if the subject has one or more subject markers identified prior to the candidate treatment, and wherein the one or more subject marker summary scores are comparable to the first reference subject’s (e.g., a patient that isdiagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have celiac disease; and who is an actual responder, i.e., demonstrates an actual therapeutic response to the candidate treatment) one or more first reference marker summary scores, then the candidate treatment is identified as being likely to have an actual therapeutic response in the subject.

[0267] In some embodiments, a method of the present disclosure comprises (1) identifying one or more treatments, wherein the one or more treatments comprise at least one candidate treatment; (2) treating or having treated at least one or more of: a first reference subject, a second reference subject, and a third reference subject with the at least one candidate treatments; (3) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the one or more first ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the one or more secondROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (c) wherein the one or more third reference markers comprise the summary score for: (i) the entire small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the entire small bowel; (ii) one or more third reference ROI of the small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the one or more third ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; and (d) wherein the one or more subject markers comprise the summary score for: (i) the entire small bowel of the subject; (ii) one or more subject ROI of the small bowel of the subject; or (iii) a combination thereof; and wherein the summary score is determined: prior to the at least one candidate treatment, or during the at least one candidate treatment; and (4) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined during the at least one candidate treatment are comparable to the one or more first reference marker summary scores of any one of (a)(i)-(iii) determined during the at least one candidate treatment, then the at least one candidate treatment is identified as having an actual therapeutic response in the subject.

[0268] For example, in some embodiments, if the subject has one or more subject markers identified during the candidate treatment, and the one or more subject marker summary scores are comparable to the first reference subject’s (e.g., a patient that is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have celiac disease; and who is an actual responder, i.e., demonstrates an actual therapeutic response to the candidate treatment) one or more first reference marker summary scores, then the candidate treatment is identified as having an actual therapeutic response in the subject.

[0269] In some embodiments, a method of the present disclosure comprises (1) identifying one or more treatments, wherein the one or more treatments comprise at least one candidate treatment; (2) treating or having treated at least one or more of: a first reference subject, a second reference subject, and a third reference subject with the at least onecandidate treatments; (3) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the one or more first ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the one or more second ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (c) wherein the one or more third reference markers comprise the summary score for: (i) the entire small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the entire small bowel; (ii) one or more third reference ROI of the small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected ofhaving, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the one or more third ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; and (d) wherein the one or more subject markers comprise the summary score for: (i) the entire small bowel of the subject; (ii) one or more subject ROI of the small bowel of the subject; or (iii) a combination thereof; and wherein the summary score is determined: prior to the at least one candidate treatment, or during the at least one candidate treatment; and (4) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined prior to the at least one candidate treatment are comparable to the one or more second reference marker summary scores of any one of (b)(i)- (iii) determined prior to the at least one candidate treatment, then the at least one candidate treatment is identified as being likely to not have an actual therapeutic response in the subject.

[0270] For example, in some embodiments, if the subject has one or more subject markers identified prior to the candidate treatment, and the one or more subject marker summary scores are comparable to the second reference subject’s (e.g., a patient that is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have celiac disease; but who is not a responder, i.e., the patient does not demonstrate a therapeutic response to the candidate treatment) one or more second reference marker summary scores, then the candidate treatment is identified as being likely to not have an actual therapeutic response in the subject.

[0271] In some embodiments, a method of the present disclosure comprises (1) identifying one or more treatments, wherein the one or more treatments comprise at least one candidate treatment; (2) treating or having treated at least one or more of: a first reference subject, a second reference subject, and a third reference subject with the at least one candidate treatments; (3) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein thefirst reference subject has an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the one or more first ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the one or more second ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (c) wherein the one or more third reference markers comprise the summary score for: (i) the entire small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the entire small bowel; (ii) one or more third reference ROI of the small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the one or more third ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; and (d) wherein the one or more subject markers comprise the summary score for: (i) the entire small bowel of the subject; (ii) one or more subject ROI of the smallbowel of the subject; or (iii) a combination thereof; and wherein the summary score is determined: prior to the at least one candidate treatment, or during the at least one candidate treatment; and (4) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined during the at least one candidate treatment are comparable to the one or more second reference marker summary scores of any one of (b)(i)- (iii) determined during the at least one candidate treatment, then the at least one candidate treatment is identified as not having an actual therapeutic response in the subject.

[0272] For example, in some embodiments, if the subject has one or more subject markers identified during the candidate treatment, and the one or more subject marker summary scores are comparable to the second reference subject’s (e.g., a patient that is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have celiac disease; but who is not a responder, i.e., the patient does not demonstrate a therapeutic response to the candidate treatment) one or more second reference marker summary scores, then the candidate treatment is identified as being not having an actual therapeutic response in the subject.

[0273] In some embodiments, a method of the present disclosure comprises (1) identifying one or more treatments, wherein the one or more treatments comprise at least one candidate treatment; (2) treating or having treated at least one or more of: a first reference subject, a second reference subject, and a third reference subject with the at least one candidate treatments; (3) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the one or more first ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least onecandidate treatment; or a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the one or more second ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (c) wherein the one or more third reference markers comprise the summary score for: (i) the entire small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the entire small bowel; (ii) one or more third reference ROI of the small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the one or more third ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; and (d) wherein the one or more subject markers comprise the summary score for: (i) the entire small bowel of the subject; (ii) one or more subject ROI of the small bowel of the subject; or (iii) a combination thereof; and wherein the summary score is determined: prior to the at least one candidate treatment, or during the at least one candidate treatment; and (4) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined prior to the at least one candidate treatment are comparable to the one or more third reference marker summary scores of any one of (c)(i)- (iii) determined prior to the at least one candidate treatment, then the at least one candidate treatment is identified as being likely to have an actual adverse response in the subject.

[0274] For example, in some embodiments, if the subject has one or more subject markers identified prior to the candidate treatment, and the one or more subject marker summary scores are comparable to the third reference subject’s (e.g., a patient that is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have celiac disease; and who has had an adverse reaction to the candidate treatment) one or more third reference marker summary scores, then the candidate treatment is identified as being likely to have an actual adverse response in the subject.

[0275] In some embodiments, a method of the present disclosure comprises (1) identifying one or more treatments, wherein the one or more treatments comprise at least one candidate treatment; (2) treating or having treated at least one or more of: a first reference subject, a second reference subject, and a third reference subject with the at least one candidate treatments; (3) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the one or more first ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy inthe one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the one or more second ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (c) wherein the one or more third reference markers comprise the summary score for: (i) the entire small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the entire small bowel; (ii) one or more third reference ROI of the small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the one or more third ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; and (d) wherein the one or more subject markers comprise the summary score for: (i) the entire small bowel of the subject; (ii) one or more subject ROI of the small bowel of the subject; or (iii) a combination thereof; and wherein the summary score is determined: prior to the at least one candidate treatment, or during the at least one candidate treatment; and (4) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined during the at least one candidate treatment are comparable to the one or more third reference marker summary scores of any one of (c)(i)- (iii) determined during the at least one candidate treatment, then the at least one candidate treatment is identified as having an actual adverse response in the subject.

[0276] For example, in some embodiments, if the subject has one or more subject markers identified prior to the candidate treatment, and the one or more subject marker summary scores are comparable to the third reference subject’s (e.g., a patient that is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have celiac disease; and who has had an adverse reaction to the candidate treatment) one or more third reference marker summary scores, then the candidate treatment is identified as having an actual adverse response in the subject.

[0277] In some embodiments, a method of the present disclosure comprises (1) identifying one or more treatments, wherein the one or more treatments comprise at least onecandidate treatment; (2) treating or having treated at least one or more of: a first reference subject, a second reference subject, and a third reference subject with the at least one candidate treatments; (3) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the one or more first ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the entire small bowel; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the one or more second ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; (c) wherein the one or more third reference markers comprise the summary score for: (i) the entire small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in theentire small bowel; (ii) one or more third reference ROI of the small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the one or more third ROI; or (iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; and (d) wherein the one or more subject markers comprise the summary score for: (i) the entire small bowel of the subject; (ii) one or more subject ROI of the small bowel of the subject; or (iii) a combination thereof; and wherein the summary score is determined: prior to the at least one candidate treatment, or during the at least one candidate treatment; and (4) comparing the at least two or more markers; wherein if the one or more subject marker summary scores determined prior and during the at least one candidate treatment are comparable to either the: one or more first reference marker summary scores of any one of (a)(i)-(iii), one or more second reference marker summary scores of any one of (b)(i)-(iii), one or more third reference marker summary scores of any one of (c)(i)-(iii), as determined prior and during at least one candidate treatment; then the at least one candidate treatment is identified: as having an actual therapeutic response in the subject over time; not having an actual therapeutic response in the subject over time; or having actual adverse response in the subject over time; respectively.

[0278] For example, in some embodiments, a method of the present disclosure comprises: identifying at least one candidate treatment for an enteropathy (e.g., celiac disease) in a subject in need thereof; wherein the candidate treatment has been administered to the following reference subjects:• a first reference subject (e.g., a patient that is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have celiac disease; and who is an actual responder, i.e., demonstrates a therapeutic response to the candidate treatment);• a second reference subject (e.g., a patient that is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have celiac disease; but who is not a responder, i.e., the patient does not demonstrate a therapeutic response to the candidate treatment); and• a third reference subject (e.g., a patient that is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have celiac disease; and who has had an adverse reaction to the candidate treatment)

[0279] Next, markers will be identified in the subject, and in one or more reference subjects (e.g., a first, second, and / or third reference subject), wherein the markers comprise a summary score — e.g., as described herein, such as the summary of damage as determined, e.g., based on the level or intensity of villous atrophy and / or injury, along the entire small bowel of a subject and / or one or more regions of interest (ROI) therein. Thus, the subject, first reference subject, second reference subject, and third reference subject, will each have a respective marker comprising the summary score for the entire small bowel and / or one or more ROI therein, i.e., one or more subject markers; one or more first reference markers, one or more second reference markers, and one or more third reference markers.

[0280] In addition, in some embodiments, the subject’s markers will be monitored and / or evaluated over time, e.g., the one or more subject markers, e.g., the subject’s summary score for the entire small bowel and / or one or more subject ROI therein, may be determined prior to administration with a candidate treatment to the subject in need thereof, and at one or more time points subsequent to the administration of the candidate treatment.

[0281] Thus, in some embodiments, once the biomarkers have been identified, they can be compared to not only identify a suitable candidate treatment for the subject, but to also monitor the effect of said candidate treatment over time. For example, in some embodiments, the one or more subject markers can be compared to the one or more first reference markers, the one or more second reference markers, and / or the one or more third reference markers (collectively the “reference markers”); wherein the one or more subject markers are compared to the reference markers prior to the administration of the candidate treatment; during the administration of the candidate treatment; and / or after the administration of the candidate treatment.

[0282] Thus, in some embodiments, the one or more subject markers can be compared to the reference markers prior to the administration of the candidate treatment (to identify whether the subject is a suitable recipient of the candidate treatment); during the administration of the candidate treatment (to determine whether the subject is responding to the candidate treatment, e.g., showing a therapeutic response); and / or after the administration of the candidate treatment (e.g., to determine the reduction in severity and / or resolution of the enteropathy in response to the candidate treatment).

[0283] In some embodiments, any of the foregoing methods can be used to screen one or more subjects in a clinical trial.

[0284] The present disclosure describes methods of identifying one or more markers in the small bowel of a subject, the method comprising: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof.

[0285] In some embodiments, a method of the present disclosure comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the ordinal scale comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy.

[0286] In some embodiments, a method of the present disclosure comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more indicators of small bowel injury are: a villous height / crypt depth (Vh:Cd) ratio; an enzyme-linked immunosorbent spot (ELISpot) assay; an IL-2 serology assay; a CD4 assay; a CD8 assay; anintraepithelial lymphocytes (IEL) count; a Marsh score; a patient-reported outcome assessment; or villous atrophy.

[0287] In some embodiments, a method of the present disclosure comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more indicators of small bowel injury are villous atrophy.

[0288] In some embodiments, a method of the present disclosure comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more indicators of small bowel injury are villous atrophy as determined via a visual assessment of one or more image frames selected from: one or more photographic image frames; one or more sonographic image frames; one or more radiographic image frames; one or more confocal image frames; or one or more tomographic image frames.

[0289] In some embodiments, a method of the present disclosure comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowelof the subject; or (c) any combination thereof; wherein the one or more indicators of small bowel injury are one or more photographic image frames.

[0290] In some embodiments, a method of the present disclosure comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more indicators of small bowel injury are one or more frames of a video.

[0291] In some embodiments, the one or more image frames, e.g., the one or more photographic image frames; one or more sonographic image frames; one or more radiographic image frames; one or more confocal image frames; or one or more tomographic image frames; can be obtained from a device such as an ingestible camera, an endoscope, a celioscope, a laparoscope, an ultrasonic scanner, an X-ray detector, a computed tomography scanner, a positron emission tomography scanner, a magnetic resonance tomography scanner, an optical coherence tomography scanner, or a confocal microscope.

[0292] The use of such devices, i.e., an ingestible camera, an endoscope, a celioscope, a laparoscope, an ultrasonic scanner, an X-ray detector, a computed tomography scanner, a positron emission tomography scanner, a magnetic resonance tomography scanner, an optical coherence tomography scanner, and / or a confocal microscope, is known in the art.

[0293] In some embodiments, the one or more image frames, e.g., the one or more photographic image frames, can be obtained with a video capsule endoscope.

[0294] Video-Capsule Endoscopy (VCE)

[0295] Video-Capsule Endoscopy (VCE) is a safe alternative for imaging intestinal mucosa and is less invasive than EGD with duodenal biopsy; patients can better tolerate it and the procedure can evaluate the entire small intestine. Head-to-head trials comparing VCE systems have shown completion rates for visualizing the small intestine, ranging from 59% to 100%, with most systems having a rate over 80%. VCE is traditionally evaluated frame by frame in video compilation by an experienced gastroenterologist for the presence or absence of an enteropathy (e.g., celiac disease and its complications). The gastroenterologist then provides a final assessment of the entire small bowel (SB), in some cases measured asminutes of celiac and the gastroenterologist global impression of injury severity. Other non- VCE measures of enteropathy diagnosis or severity are histology and serology.

[0296] The accepted standard for the measurement of villous damage due to CeD has been the determination of villous height and crypt depth from endoscopic biopsy samples obtained in the duodenum. As described herein, the use of VCE to image the entire small bowel presents an opportunity to evaluate villous health throughout the entire length of the SB. Indeed, present day VCE videos have sufficient resolution to determine the villous health of each video frame. See Metzger et al. Comparison of a new PillCam™ SB2 video capsule versus the standard PillCam™ SB for detection of small bowel disease. Reports in Medical Imaging. 2009;2:7-11 ; the disclosure of which is incorporated herein in its entirety.

[0297] In some embodiments, an ordinal Likert-like scale of villous atrophy in histopathology may be used. See Vecsei A, Amann G, Hegenbart S, Liedlgruber M, Uhl A. Automated Marsh-like classification of celiac disease in children using local texture operators. Computers in Biology and Medicine. 2011 ;41 (6):313-325 ; ; the disclosure of which is incorporated herein in its entirety.

[0298] In some embodiments, a method of present disclosure comprises identifying one or more markers in the small bowel of a subject, the method comprising: (1) capturing one or more frames of a video of the small bowel of the subject; (2) determining an injury score for each of the one or more frames of the video, wherein the injury score comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof.

[0299] Accordingly, in some embodiments, the injury score described above is an ordinal scale that represents a continuum of villous damage for each frame of a VCE video, that provides a sensitive measure the extent of small bowel injury (or lack thereof) in regions of interest throughout the SB. The advantage of obtaining a frame-by-frame score for the entirety of the SB length is the ability to summarize villous health by calculating a summary score for a chosen region of interest that reliably reflects the assessments of gastroenterologist readers expert in the evaluation of VCE for subjects in need of treatment (e.g., CeD patients). Further, in some embodiments, the images collected by the capsuleendoscopy camera are white light representations of the gross pathology of the villi, and villous damage is conspicuous on gross pathology.

[0300] In some embodiments, the ordinal scale described above may be supplemented with qualitative descriptions of changes in injury, observable with VCE, including descriptors such as “scalloping,” “fissuring,” “mosaic,” “effacement” or “absence of folds,” “villous atrophy,” “absent villi,” “blunting of villi,” and “flat mucosa.” In some embodiments, the foregoing descriptors may be scored and / or normalized in order to properly define the relationship among these descriptions of disease manifestations, and allow consistency while maintaining the readers’ independence.

[0301] In some embodiments, a method of the present disclosure comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject; (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the ordinal scale comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy.

[0302] In some embodiments, the present disclosure describes a method of identifying one or more markers in the small bowel of a subject, the method comprising: (1) capturing one or more frames of a video of the small bowel of the subject; (2) determining an injury score for each of the one or more frames of the video, wherein the injury score comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof.

[0303] In some embodiments, the one or more image frames described above can be obtained from any imaging device known in the art capable of image production, e.g., including but not limited to at least one of the following: photographic image frames (e.g.,single image frames or one or more photographic image frames such as in a video), sonographic image frames, radiographic image frames, confocal image frames, or tomographic image frames.

[0304] One example embodiment may include the methods above, wherein the at least one imaging device includes at least one device selected from the group consisting of an ingestible camera, an endoscope, a celioscope, a laparoscope, an ultrasonic scanner, an X-ray detector, a computed tomography scanner, a positron emission tomography scanner, a magnetic resonance tomography scanner, an optical coherence tomography scanner, and a confocal microscope.

[0305] In some embodiments, a method of identifying one or more markers in the small bowel of a subject, comprises: (1) capturing one or more frames of a video of the small bowel of the subject using Video-Capsule Endoscopy (VCE); (2) determining a Celiac Enteropathy Villous Atrophy Scale (CE-VAST) score for each of the one or more frames of the video, wherein the CE-VAST score comprises a level of injury intensity ranging from 0- 3, wherein 0 is no visual villous atrophy; and wherein 3 is complete visual villous atrophy; (3) generating a Mucosal AtRophy Celiac Scale (MARCS) score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof, by calculating: (a) a curve fit to the CE-VAST score for each of the one or more frames of the video provided in Step (2), for the entirety of the small bowel of the subject, and using equally spaced points therein; and (b) a mean CE-VAST score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the MARCS score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the one or more markers are indicative of one or more of: (i) Celiac disease (CeD), or a lack thereof; (ii) a level of severity of Celiac disease (CeD) for the entirety of the small bowel, or one or more ROI therein; (iii) a likely therapeutic or adverse response of a treatment for Celiac disease (CeD) for the entirety of the small bowel, or one or more ROI therein, in a subject in need thereof; or (iv) an actual therapeutic or adverse response of a treatment for Celiac disease (CeD) for the entirety of the small bowel, or one or more ROI therein, in a subject in need thereof.

[0306] In some embodiments, the Celiac Enteropathy Villous Atrophy Scale (CE- VAST) score can be determined using one or more Artificial Intelligence (Al) approaches. Al approaches are described in detail below.

[0307] Artificial Intelligence (Al) approaches

[0308] Any of the methods described herein, e.g., determining an injury score and / or generating a summary score, can be performed using any one or more artificial intelligence (Al) approaches known to those having ordinary skill in the art. As used herein, the term “artificial intelligence approaches” refers to approaches, algorithms, architectures, and methodologies (e.g., machine learning approaches, etc.), that may be used to practice the methods of the present disclosure, including any one or more of: supervised learning (e.g., using logistic regression, using back propagation neural networks, using random forests, decision trees, etc.); unsupervised learning (e.g., using an Apriori algorithm, using K- means clustering); semi-supervised learning; a deep learning algorithm (e.g., neural networks, a restricted Boltzmann machine, a deep belief network method, a convolutional neural network method, a recurrent neural network method, stacked auto-encoder method, etc.); reinforcement learning (e.g., using a Q-learning algorithm, using temporal difference learning); a regression algorithm (e.g., ordinary least squares, logistic regression, stepwise regression, multivariate adaptive regression splines, locally estimated scatterplot smoothing, etc.); an instance-based method (e.g., k-nearest neighbor, learning vector quantization, selforganizing map, etc.); a regularization method (e.g., ridge regression, least absolute shrinkage and selection operator, elastic net, etc.); a decision tree learning method (e.g., classification and regression tree, iterative dichotomiser 3, C4.5, chi-squared automatic interaction detection, decision stump, random forest, multivariate adaptive regression splines, gradient boosting machines, etc.); a Bayesian method (e.g., naive Bayes, averaged one-dependence estimators, Bayesian belief network, etc.); a kernel method (e.g., a support vector machine, a radial basis function, a linear discriminate analysis, etc.); a clustering method (e.g., k-means clustering, expectation maximization, etc.); an associated rule learning algorithm (e.g., an Apriori algorithm, an Eclat algorithm, etc.); an artificial neural network model (e.g., a Perceptron method, a back-propagation method, a Hopfield network method, a selforganizing map method, a learning vector quantization method, etc.); a dimensionality reduction method (e.g., principal component analysis, partial least squares regression, Sammon mapping, multidimensional scaling, projection pursuit, etc.); an ensemble method (e.g., boosting, bootstrapped aggregation, AdaBoost, stacked generalization, gradientboosting machine method, random forest method, etc.); and / or any suitable artificial intelligence approach.

[0309] In some embodiments, any of the above approaches, algorithms, architectures, methodologies, attributes, and / or features may be combined with one or more other approaches algorithms, architectures, methodologies, attributes, and / or features, wherein the approaches, algorithms, architectures, methodologies, attributes, and / or features are the same or different.

[0310] For example, in some embodiments, a first artificial intelligence approach, machine learning algorithm, and / or architecture (e.g., neural network methods, convolutional neural networks, recurrent neural networks, etc.) may be combined with a second artificial intelligence approach, algorithm, architecture, methodology, attribute, and / or feature, wherein the first and the second artificial intelligence approach can be the same and / or different.

[0311] Exemplary artificial intelligence approaches are described in U.S. Patent Nos. 11,610,645; 11,587,643; and 11,482,305; the disclosures of which are incorporated herein by reference in their entireties.

[0312] Tools and methods of training ML algorithms

[0313] In some embodiments, a machine learning (ML) approach may be implemented to evaluate one or more indicators of small bowel injury. For example, in some embodiments, a ML approach may be implemented to evaluate one or more indicators of small bowel injury such as villous atrophy as determined via a visual assessment of one or more image frames. An ML system may be trained using annotated (e.g., by a human expert) image frames of the small bowel of one or more subjects and supervised learning techniques. Additionally or alternatively, the ML system may be trained using unannotated image frames using semi-supervised or unsupervised learning techniques.

[0314] In some embodiments, a supervised machine learning (ML) may be implemented to evaluate one or more indicators of small bowel injury such as villous atrophy, as determined via a visual assessment of one or more image frames. Supervised ML can be used to accurately reproduce a human (expert) evaluation of one or more image frames (e.g., one or more frames of a video, such as those obtained from VCE).

[0315] In some embodiments, a supervised deep learning algorithm can be developed to regress the injury intensity directly from the one or more frames of the video. For example, in some embodiments, a supervised deep learning algorithm can be developed to regress the level of injury intensity directly from the one or more frames of the video; wherein the injuryintensity ranges from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy.

[0316] In yet other embodiments, a supervised deep learning algorithm can be developed to regress the celiac intensity directly from frames of the video.

[0317] In some embodiments, a supervised deep learning algorithm can be trained to regress the level of injury intensity according to methods known in the art, and described herein. For example, in some embodiments, one or more frames of a video can be obtained from: (1) a subject diagnosed with, or is confirmed to have, an enteropathy; and (2) a subject confirmed as not having an enteropathy. The level of injury intensity at each frame in the training set can be found by fitting curves through frames scored by a non-expert reader.

[0318] In some embodiments, the per frames scores provided by the algorithm may be post processed to generate curves and derived metrics in the same way that the manual scores are processed.

[0319] In some embodiments, a tool is provided that provides a method to rate the quality of the frames, wherein the tool presents a human reader with a subset of the frames informed by the enteropathy biology, and asks the reader to score frames. In some embodiments, the tool is interactive, and adaptive. In some embodiments, should a reader be uncertain about a frame’s informativeness, the reader may return the frame and be offered another.

[0320] In some embodiments, the tool presents shuffled frames to the reader randomly, to avoid bias. In some embodiments, the scored frames are sorted by position, and a visual (a curve) and a mathematical (curve derived metrics) representation of the frames is produced.

[0321] Exemplary methods of tools and training methods of artificial intelligence are provided in U.S. Patent Nos.: 11,551,786; and 11,551,357; the disclosures of which are incorporated herein by reference in their entireties.

[0322] In some embodiments, a method of the present disclosure comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject (e.g., villous atrophy as determined via a visual assessment of one or more image frames, such as one or more frames of a video); (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summaryscore generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the injury score and / or the summary score is determined by a machine learning (ML) system, artificial neural network, artificial intelligence, or large language model (LLM).

[0323] In some embodiments, a method of the present disclosure comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject (e.g., villous atrophy as determined via a visual assessment of one or more image frames, such as one or more frames of a video); (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the injury score is determined by a machine learning (ML) system, artificial neural network, artificial intelligence, or large language model (LLM).

[0324] In some embodiments, a method of the present disclosure comprises: (1) capturing one or more indicators of small bowel injury in the small bowel of the subject (e.g., villous atrophy as determined via a visual assessment of one or more image frames, such as one or more frames of a video); (2) assigning an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale; (3) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and (4) identifying the one or more markers by assigning the summary score generated in Step (3) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the injury score is determined by a machine learning (ML) system, artificial neural network, artificial intelligence, or large language model (LLM); and wherein ordinal scale comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy.

[0325] For example, in some embodiments, determining the injury score and / or calculating the summary score, can be accomplished using, e.g., an algorithm, such as a pattern-recognition algorithm, a classification algorithm, a machine-learning algorithm, or an artificial neural network.

[0326] In some embodiments, some embodiments, determining the injury score and / or calculating the summary score, can be accomplished using, e.g., an artificial neural network such as a feedforward neural network, a recurrent neural network, a modular neural network, or a memory network.

[0327] In some embodiments, some embodiments, determining the injury score and / or calculating the summary score, can be accomplished using, e.g., a convolutional neural network, a probabilistic neural network, a time-delay neural network, a perceptron neural network, or an autoencoder.

[0328] In some embodiments, machine learning can be implemented to interpret a stream of image frames in order to, e.g., determine an injury score and / or calculate a summary score.

[0329] Computer-implemented methods

[0330] The present disclosure describes methods of identifying markers in the small bowel of a subject, along with computer-implemented methods, systems, computer program products (e.g., a non-transitory computer readable medium), and / or combinations and subcombinations thereof, to effect the identification of said markers, as described further herein.

[0331] For example, in some embodiments, a computer-implemented method of the present disclosure comprises identifying one or more markers, the method comprising: automatically receiving, via at least one processor, one or more image frames (e.g., one or more frames of a video of the small bowel of the subject), wherein the one or more image frames (or a subset thereof) depicts the entirety of a small bowel of a subject and / or one or more regions of interest (ROI) therein; and automatically assigning, via the at least one processor, an injury score for each of the one or more frames of the video, said injury score comprising a level of injury corresponding to an ordinal scale (e.g., a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy, and wherein 3 is complete villous atrophy); automatically generating, via the at least one processor, a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and automatically identifying one or more markers, via the at least one processor, the summary score generated above to (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof.

[0332] In some embodiments, the computer-implemented method described above further comprises parsing metadata from each of the one or more image frames, wherein the metadata includes at least one of a timestamp, a position, a relative position within the entiresmall bowel of the subject; one or more regions of interest (ROI), and at least one image property.

[0333] In some embodiments, the one or more image frames can be captured by or originate from at least one imaging device capable of image production. For example in some embodiments, the imaging device can produce one or more: photographic image frames, sonographic image frames, radiographic image frames, confocal image frames, or tomographic image frames.

[0334] In some embodiments, the one or more image frames can be captured by an imaging device such as an ingestible camera, an endoscope, a celioscope, a laparoscope, an ultrasonic scanner, an X-ray detector, a computed tomography scanner, a positron emission tomography scanner, a magnetic resonance tomography scanner, an optical coherence tomography scanner, or a confocal microscope.

[0335] In some embodiments, the one or more image frames can be captured by video-capsule endoscopy.

[0336] In some embodiments, a computer-implemented method of the present disclosure comprises a method for identifying one or more markers, said method comprising: automatically receiving, via at least one processor, one or more image frames (e.g., one or more frames of a video of the small bowel of the subject), wherein the one or more image frames (or a subset thereof) depicts the entirety of a small bowel of a subject and / or one or more regions of interest (ROI) therein; automatically assigning, via the at least one processor, an injury score for each of the one or more frames of the video, said injury score comprising a level of injury corresponding to an ordinal scale (e.g., a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy, and wherein 3 is complete villous atrophy); automatically generating, via the at least one processor, a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and automatically identifying one or more markers, via the at least one processor, and based on the summary score generated above, for (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the method further comprises, based on the summary score, automatically generating, by the at least one processor, a diagnosis or identification of an enteropathy in a subject.

[0337] In some embodiments, a computer-implemented method for identifying one or more markers comprises: automatically receiving, via at least one processor, one or more image frames (e.g., one or more frames of a video of the small bowel of the subject), whereinthe one or more image frames (or a subset thereof) depicts the entirety of a small bowel of a subject and / or one or more regions of interest (ROI) therein; and automatically assigning, via the at least one processor, an injury score for each of the one or more frames of the video, said injury score comprising a level of injury corresponding to an ordinal scale (e.g., a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy, and wherein 3 is complete villous atrophy); automatically generating, via the at least one processor, a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and automatically identifying, via the at least one processor, the one or more markers based on summary score generated above, via the at least one processor, for (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof.

[0338] In some embodiments, a computer-implemented method for identifying one or more markers comprises: automatically receiving, via at least one processor, one or more image frames (e.g., one or more frames of a video of the small bowel of the subject), wherein the one or more image frames (or a subset thereof) depicts the entirety of a small bowel of a subject and / or one or more regions of interest (ROI) therein; and automatically assigning, via the at least one processor, an injury score for each of the one or more frames of the video, said injury score comprising a level of injury corresponding to an ordinal scale (e.g., a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy, and wherein 3 is complete villous atrophy); automatically generating, via the at least one processor, a summary for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; wherein the summary score comprises: (a) a curve fit to the injury score for each of the one or more image frames for the entirety of the small bowel of the subject, and using equally spaced points therein; and (b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and automatically identifying, via the at least one processor, one or more markers in the small bowel of the subject by assigning, via the at least one processor, the summary score to the entirety of the small bowel of the subject and / or one or more ROI therein; wherein the one or more markers are indicative of one or more of: (i) an enteropathy, or a lack thereof, in the subject; (ii) a level of severity of an enteropathy; (iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or (iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

[0339] In some embodiments, a computer-implemented method for diagnosing or identifying an enteropathy in a subject, comprises: (1) automatically identifying via at least one processor, at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, or a combination thereof; (a) wherein the one or more first reference markers comprise the summary score for:(1) the entire small bowel of a first reference subject, wherein the first reference subject is confirmed as not having the enteropathy; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is confirmed as not having the enteropathy in the one or more first reference ROI; or (iii) a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of a second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy in the one or more second reference ROI; or (iii) a combination thereof; and (c) wherein the one or more subject markers comprise the summary score for: (i) the entire small bowel of the subject; (ii) one or more subject ROI of the small bowel of the subject; or (iii) a combination thereof; and(2) automatically comparing, via at least one processor, the at least two or more markers; wherein the diagnosis and / or identification of the enteropathy is automatically determined, via at least one processor, based on: (i) if the one or more subject marker summary scores are comparable to the one or more first reference markers summary score, then the subject is diagnosed as not having the enteropathy; (ii) if the one or more subject marker summary scores are comparable to the one or more second reference markers summary score, then the subject is diagnosed as having the enteropathy.

[0340] In some embodiments, a computer-implemented method for determining a level of severity of an enteropathy, comprises: (1) automatically identifying, via at least one processor, at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, or a combination thereof; and (2) automatically comparing, via at least one processor, the at least two or more markers; (a) wherein the one or more first reference markers comprise the summary score for: (i) the entire small bowel of a first reference subject, wherein the first reference subject is confirmedas not having the enteropathy; (ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is confirmed as not having the enteropathy in the one or more first reference ROI; or (iii) a combination thereof; (b) wherein the one or more second reference markers comprise the summary score for: (i) the entire small bowel of a second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy; (ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy in the one or more second reference ROI; or (iii) a combination thereof; and (c) wherein the one or more subject markers comprise the summary score for: (i) the entire small bowel of the subject; (ii) one or more subject ROI of the small bowel of the subject; or (iii) a combination thereof; and automatically determining the level of severity of the enteropathy, via at least one processor, wherein if the one or more subject marker summary scores are comparable to or less than the one or more first reference markers summary scores, then the subject is determined to have a less severe enteropathy, relative to the level of severity of the enteropathy in the first reference subject; or if the one or more subject marker summary scores are comparable to or greater than the one or more second reference markers summary scores, then the subject is diagnosed as having a more severe enteropathy relative to the level of severity of the enteropathy in the second reference subject.

[0341] In some embodiments, the injury score of the foregoing computer- implemented method comprises a level of injury corresponding to an ordinal scale (e.g., an injury score comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy).

[0342] In some embodiments, the injury score of the foregoing computer- implemented method comprises a level of injury corresponding to an ordinal scale (e.g., an injury score comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy), wherein the injury score is determined using an Al approach, e.g., any one or more of: supervised learning (e.g., using logistic regression, using back propagation neural networks, using random forests, decision trees, etc.); unsupervised learning (e.g., using an Apriori algorithm, using K-means clustering); semi-supervised learning; a deep learning algorithm (e.g., neural networks, a restricted Boltzmann machine, a deep belief network method, a convolutional neural network method, a recurrent neural network method, stacked auto-encoder method, etc.); reinforcement learning(e.g., using a Q-learning algorithm, using temporal difference learning); a regression algorithm (e.g., ordinary least squares, logistic regression, stepwise regression, multivariate adaptive regression splines, locally estimated scatterplot smoothing, etc.); an instance-based method (e.g., k-nearest neighbor, learning vector quantization, self-organizing map, etc.); a regularization method (e.g., ridge regression, least absolute shrinkage and selection operator, elastic net, etc.); a decision tree learning method (e.g., classification and regression tree, iterative dichotomiser 3, C4.5, chi-squared automatic interaction detection, decision stump, random forest, multivariate adaptive regression splines, gradient boosting machines, etc.); a Bayesian method (e.g., naive Bayes, averaged one-dependence estimators, Bayesian belief network, etc.); a kernel method (e.g., a support vector machine, a radial basis function, a linear discriminate analysis, etc.); a clustering method (e.g., k-means clustering, expectation maximization, etc.); an associated rule learning algorithm (e.g., an Apriori algorithm, an Eclat algorithm, etc.); an artificial neural network model (e.g., a Perceptron method, a back- propagation method, a Hopfield network method, a self-organizing map method, a learning vector quantization method, etc.); a dimensionality reduction method (e.g., principal component analysis, partial least squares regression, Sammon mapping, multidimensional scaling, projection pursuit, etc.); an ensemble method (e.g., boosting, bootstrapped aggregation, AdaBoost, stacked generalization, gradient boosting machine method, random forest method, etc.); and / or any suitable artificial intelligence approach.

[0343] In some embodiments, the injury score comprises a level of injury corresponding to an ordinal scale (e.g., an injury score comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy), and is determined using an algorithm, e.g., a pattern-recognition algorithm, a classification algorithm, a machine-learning algorithm, or at least one artificial neural network.

[0344] In some embodiments, the summary score, e.g., the calculation of (a) a curve fit to the injury score for each of the one or more image frames for the entirety of the small bowel of the subject, and using equally spaced points therein; and (b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject and / or one or more regions of interest (ROI) therein, is generated using an algorithm, e.g., a pattern-recognition algorithm, a classification algorithm, a machine-learning algorithm, or at least one artificial neural network.

[0345] In some embodiments, any of the computer-implemented methods described herein can further comprise receiving, via the at least one processor, information about thegiven subject’s disease state, medical history, demographics (e.g., age, height, weight, gender, etc.), nutritional habits, and / or lab tests; and passing, via the at least one processor, the information as input to the algorithm.

[0346] In some embodiments, the summary score, e.g., the calculation of (a) a curve fit to the injury score for each of the one or more image frames for the entirety of the small bowel of the subject, and using equally spaced points therein; and (b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject and / or one or more regions of interest (ROI) therein, is generated using an algorithm, e.g., at least one artificial neural network, wherein the at least one artificial neural network includes at least one of a feedforward neural network, a recurrent neural network, a modular neural network, or a memory network.

[0347] In some embodiments, the summary score, e.g., the calculation of (a) a curve fit to the injury score for each of the one or more image frames for the entirety of the small bowel of the subject, and using equally spaced points therein; and (b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject and / or one or more regions of interest (ROI) therein, is generated using an algorithm, e.g., a least one artificial neural network such as a feedforward neural network, wherein the feedforward neural network corresponds to at least one of a convolutional neural network, a probabilistic neural network, a time-delay neural network, a perceptron neural network, or an autoencoder.

[0348] In some embodiments, a computer-implemented method of the present disclosure comprises: automatically receiving, via at least one processor, one or more image frames (e.g., one or more frames of a video) of the small bowel of the subject; automatically determining an injury score for each of the one or more frames, by automatically inputting each of the one or more image frames into an artificial neural network, wherein the injury score has a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy; automatically calculating, via the at least one processor, a summary score comprising: (a) a curve fit to the injury score for each of the one or more frames of the video for the entirety of the small bowel of the subject, and using equally spaced points therein; and (b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and automatically identifyi...

Claims

CLAIMS1. A computer-implemented method comprising: receiving an indication of: a first selection corresponding to an image that represents a portion of an internal cavity of an organ associated with a subject; or a second selection corresponding to a coordinate on a curve of a plot representing a quantitative metric that characterizes a region of the internal cavity of the organ associated with the subject; in response to the received indication, when the received indication corresponds to the first selection, determining a respective coordinate on the curve of the plot representing the quantitative metric that characterizes the region of the internal cavity of the organ, wherein the respective coordinate indicates a position in the internal cavity where the image was captured, and a value for the quantitative metric at the position where the image was captured; when the received indication corresponds to the second selection, determining a respective image captured to represent the portion of the internal cavity of the organ associated with the subject, wherein the respective image was captured at a respective position corresponding to the coordinate indicated by the second selection; and displaying, at a graphical user interface: the coordinate or the respective coordinate in a first viewing window of the graphical user interface; and the image or the respective image in a second viewing window of the graphical user interface.

2. The method of claim 1 , wherein the image is associated with a set of images from an endoscopy of the subject.

3. The method of claim 1, wherein the image is captured by a video capsule.

4. The method of claim 3, wherein the video capsule has at least a 170 degree field of view.

5. The method of claim 3, wherein the video capsule is capable of a 360 degree field of view.

6. The method of claim 1 , wherein displaying the coordinate and the image further comprises simultaneously displaying the coordinate and the image at the graphical user interface such that the coordinate and the image are observable by a user of the graphical user interface at the same time.

7. The method of claim 1, wherein displaying a first one of the coordinate or the respective coordinate and a second one of the image or the respective image further comprises simultaneously displaying the first one and the second one at the graphical user interface such that the first one and the second one are observable by a user of the graphical user interface at the same time.

8. A computer-implemented method comprising: receiving medical imaging data characterizing a set of regions of the small bowel of a subject; processing the medical imaging data to generate a graphical representation that indicates an extent of enteropathy for the subject throughout the set of regions of the small bowel; and displaying, at a graphical user interface, the graphical representation simultaneously with corresponding medical imaging data such that: the graphical representation and the corresponding medical imaging data are observable by a user of the graphical user interface at the same time; and an element of the graphical representation is visually associated with a portion of the medical imaging data that generated the element.

9. The method of claim 8, wherein the graphical representation is rendered in a first viewing window and the corresponding medical imaging data is rendered in a second viewing window.

10. The method of any of claims 8 and 9, wherein the medical imaging data includes a set of images captured from an endoscopy of the subject.

11. The method of claim 10, wherein the set of images is captured by video capsule endoscopy.

12. A computer-implemented method comprising: receiving, at data processing hardware, a plurality of images capturing an extent of an internal cavity of an organ for a subject; for each image, determining, by the data processing hardware, a severity score that characterizes a degree of enteropathy for tissue within the internal cavity of the organ represented in the respective image; generating, by the data processing hardware, a graphical curve representing an intensity of injury for the tissue of the organ, wherein the graphical curve includes a set of points for the subject, wherein each point corresponds to the respective image and includes a coordinate pair identifying a position within the organ where the respective image was captured and the corresponding severity score for the respective image; classifying, by the data processing hardware, the graphical curve as a phenotype of enteropathy, and determining, by the data processing hardware, that the classified phenotype matches a stored phenotype of enteropathy; optionally, wherein the stored phenotype of enteropathy corresponds to a diagnosed disease state.

13. The method of claims 12, further comprising communicating an indication that the classified phenotype matches the stored phenotype to a graphical user interface of a user device in communication with the data processing hardware.

14. A method of identifying a marker of an enteropathy in a subject, the method comprising:receiving data corresponding to one or more indicators of small bowel injury in the subject; processing the one or more indicators of small bowel injury; and generating a representation of the one or more indicators of the small bowel injury.

15. The method of claim 14, further comprising reporting the representation of the one or more indicators of the small bowel injury.

16. The method of claim 14, wherein generating the representation comprises generating an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale.

17. The method of claim 16, further comprising generating a summary score for:(a) the entire small bowel of the subject;(b) one or more regions of interest (ROI) of the small bowel of the subject; or(c) any combination thereof.

18. The method of claim 16, further comprising identifying the marker by assigning the summary score to:(a) the entire small bowel of the subject;(b) one or more regions of interest (ROI) of the small bowel of the subject; or(c) any combination thereof.

19. The method of any one of claims 14-18, wherein the one or more indicators of small bowel injury are: a villous height / crypt depth (Vh:Cd) ratio; an enzyme-linked immunosorbent spot (ELISpot) assay; an IL-2 serology assay; a CD4 assay; a CD8 assay; an intraepithelial lymphocytes (IEL) count; a Marsh score; a patient-reported outcome assessment; or villous atrophy.

20. The method of claim 19, wherein the level of injury ranges from 0-10, wherein 0 corresponds to no villous atrophy; and wherein 10 corresponds to complete villous atrophy; from0-9, wherein 0 corresponds to no villous atrophy; and wherein 9 corresponds to complete villous atrophy; from 0-8, wherein 0 corresponds to no villous atrophy; and wherein 8 corresponds to complete villous atrophy; from 0-7, wherein 0 corresponds to no villous atrophy; and wherein 7 corresponds to complete villous atrophy; from 0-6, wherein 0 corresponds to no villous atrophy; and wherein 6 corresponds to complete villous atrophy; from 0-5, wherein 0 corresponds to no villous atrophy; and wherein 5 corresponds to complete villous atrophy; from 0-4, wherein 0 corresponds to no villous atrophy; and wherein 4 corresponds to complete villous atrophy; or from 0-3 wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy.

21. The method of claim 20, wherein the level of injury ranges from 0-3, wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy.

22. The method of claim 16-21, wherein the level of injury is determined via: a visual assessment; a level or amount of fluorescence; a level or amount of radioactivity; a microscopic examination; a histopathological assessment; an assessment of the average height of the villi relative to the average depth of the crypts in a biopsy sample; or an assessment of the number of lymphocytes relative to the number of enterocytes (intestinal epithelial cells).

23. The method of claim 22, wherein the visual assessment is one or more image frames.

24. The method of claim 23, wherein the visual assessment is two or more image frames.

25. The method of claim 23, wherein the one or more image frames are one or more photographic image frames; one or more sonographic image frames; one or more radiographic image frames; one or more confocal image frames; or one or more tomographic image frames.

26. The method of claim 25, wherein the one or more image frames are one or more photographic image frames.

27. The method of claim 26, wherein the one or more photographic image frames are one or more frames of a video.

28. The method of claim 24, wherein the two or more image frames are two or more frames of a video.

29. The method of any one of claims 23-28, wherein the injury score is determined for each of the one or more images frames, or for each of the two or more image frames.

30. The method of claim 29, wherein the two or more image frames are obtained circumferentially and / or proximodistally along the interior of the small bowel of the subject.

31. The method of any one of claims 17-30, wherein the summary score is generated by calculating:(a) a curve fit to the injury score for each of the one or more frames of the video, for the entirety of the small bowel of the subject, and using equally spaced points therein; and(b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof.

32. The method any one of claims 14-31, wherein the marker is indicative of one or more of:(i) an enteropathy, or a lack thereof, in the subject;(ii) a level of severity of an enteropathy;(iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or(iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

33. The method of any one of claims 14-32, wherein the marker is identified for:(a) the entire small bowel of:(i) a subject confirmed as not having an enteropathy;(ii) a plurality of subjects, wherein each subject of the plurality of subjects are independently confirmed as not having an enteropathy;(iii) a subject diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy;(iv) a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy; or(b) one or more regions of interest (ROI), comprising:(i) one or more ROI of the small bowel of a subject, wherein the subject is confirmed as not having an enteropathy in the one or more ROI;(ii) a plurality of one or more ROI of the small bowels of a plurality of subjects, wherein each subject of the plurality of subjects are independently confirmed as not having an enteropathy in the one or more ROIs;(iii) one or more ROI of the small bowel of a subject, wherein the subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy in the one or more ROI;(iv) a plurality of one or more ROI of the small bowels of a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy in the one or more ROI.

34. The method of any one of claims 14-33, wherein the marker is identified:(a) prior to treating or having treated the subject with a treatment for the enteropathy;(b) during the treatment of the subject for the enteropathy;(c) after treating the subject with the treatment for the enteropathy;(d) during at least two time points, wherein the two time points are selected from: one or more time points prior to the treatment of the subject, one or more time points during the treatment of the subject, or one or more time points after the treatment of the subject, for the enteropathy; or(e) to establish a reference marker indicative of an enteropathy, or a lack thereof, in a subject diagnosed with or confirmed to have the enteropathy.

35. The method of any one of claims 14-34, wherein the marker is a biomarker, or a data- driven marker.

36. The method of claim 35, wherein the marker is data-driven marker.

37. A method of identifying a data-driven marker in the small bowel of a subject, the method comprising: receiving data corresponding to one or more indicators of small bowel injury in the subject; processing the one or more indicators of small bowel injury; generating a behavioral prediction to address the one or more indicators of small bowel injury; and communicating the behavioral prediction.

38. The method of claim 37, wherein the behavioral prediction comprises one or more of a medical recommendation, a dietary recommendation, a behavior change, or a drug prescription.

39. The method of claim 38, further comprising, generating a representation of the one or more indicators of the small bowel injury.

40. The method of claim 39, wherein generating the representation comprises generating an injury score for each of the one or more indicators of small bowel injury, wherein the injury score comprises a level of injury corresponding to an ordinal scale.

41. The method of claim 40, further comprising generating a summary score for:(a) the entire small bowel of the subject;(b) one or more regions of interest (ROI) of the small bowel of the subject; or(c) any combination thereof.

42. The method of claim 41, further comprising identifying a data-driven marker by assigning the summary score to:(a) the entire small bowel of the subject;(b) one or more regions of interest (ROI) of the small bowel of the subject; or(c) any combination thereof.

43. The method of any one of claims 37-42, wherein the one or more indicators of small bowel injury are: a villous height / crypt depth (Vh:Cd) ratio; an enzyme-linked immunosorbent spot (ELISpot) assay; an IL-2 serology assay; a CD4 assay; a CD8 assay; an intraepithelial lymphocytes (IEL) count; a Marsh score; a patient-reported outcome assessment; or villous atrophy.

44. The method of claim 43, wherein the level of injury ranges from 0-10, wherein 0 corresponds to no villous atrophy; and wherein 10 corresponds to complete villous atrophy; from 0-9, wherein 0 corresponds to no villous atrophy; and wherein 9 corresponds to complete villous atrophy; from 0-8, wherein 0 corresponds to no villous atrophy; and wherein 8 corresponds to complete villous atrophy; from 0-7, wherein 0 corresponds to no villous atrophy; and wherein 7 corresponds to complete villous atrophy; from 0-6, wherein 0 corresponds to no villous atrophy; and wherein 6 corresponds to complete villous atrophy; from 0-5, wherein 0 corresponds to no villous atrophy; and wherein 5 corresponds to complete villous atrophy; from 0-4, wherein 0 corresponds to no villous atrophy; and wherein 4 corresponds to complete villous atrophy; or from 0-3 wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy.

45. The method of claim 44, wherein the level of injury ranges from 0-3, wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy.

46. The method of claim 40-45, wherein the level of injury is determined via: a visual assessment; a level or amount of fluorescence; a level or amount of radioactivity; a microscopic examination; a histopathological assessment; an assessment of the average height of the villi relative to the average depth of the crypts in a biopsy sample; or an assessment of the number of lymphocytes relative to the number of enterocytes (intestinal epithelial cells).

47. The method of claim 46, wherein the visual assessment one or more image frames.

48. The method of claim 47, wherein the visual assessment is two or more image frames.

49. The method of claim 47, wherein the one or more image frames are one or more photographic image frames; one or more sonographic image frames; one or more radiographic image frames; one or more confocal image frames; or one or more tomographic image frames.

50. The method of claim 49, wherein the one or more image frames are one or more photographic image frames.

51. The method of claim 50, wherein the one or more photographic image frames are one or more frames of a video.

52. The method of claim 48, wherein the two or more image frames are two or more frames of a video.

53. The method of any one of claims 47-52, wherein the injury score is determined for each of the one or more images frames, or for each of the two or more image frames.

54. The method of claim 53, wherein the two or more image frames are obtained circumferentially and / or proximodistally along the interior of the small bowel of the subject.

55. The method of any one of claims 37-54, wherein the summary score is generated by calculating:(a) a curve fit to the injury score for each of the one or more frames of the video, for the entirety of the small bowel of the subject, and using equally spaced points therein; and(b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof.

56. The method any one of claims 37-55, wherein the data-driven marker is indicative of one or more of:(i) an enteropathy, or a lack thereof, in the subject;(ii) a level of severity of an enteropathy;(iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or(iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

57. The method of any one of claims 37-56, wherein the data-driven marker is identified for:(a) the entire small bowel of:(i) a subject confirmed as not having an enteropathy;(ii) a plurality of subjects, wherein each subject of the plurality of subjects are independently confirmed as not having an enteropathy;(iii) a subject diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy;(iv) a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy; or(b) one or more regions of interest (ROI), comprising:(i) one or more ROI of the small bowel of a subject, wherein the subject is confirmed as not having an enteropathy in the one or more ROI;(ii) a plurality of one or more ROI of the small bowels of a plurality of subjects, wherein each subject of the plurality of subjects are independently confirmed as not having an enteropathy in the one or more ROIs;(iii) one or more ROI of the small bowel of a subject, wherein the subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy in the one or more ROI;(iv) a plurality of one or more ROI of the small bowels of a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy in the one or more ROI.

58. The method of any one of claims 37-57, wherein the data-driven marker is identified:(a) prior to treating or having treated the subject with a treatment for the enteropathy;(b) during the treatment of the subject for the enteropathy;(c) after treating the subject with the treatment for the enteropathy;(d) during at least two time points, wherein the two time points are selected from: one or more time points prior to the treatment of the subject, one or more time points during the treatment of the subject, or one or more time points after the treatment of the subject, for the enteropathy; or(e) to establish one or more reference markers indicative of an enteropathy, or a lack thereof, in a subject diagnosed with or confirmed to have the enteropathy.

59. A method of identifying a marker of an enteropathy, or lack thereof, in the small bowel of a subject, the method comprising: receiving medical data characterizing a set of regions of the small bowel of the subject; and for the received endoscopy data, generating, by data processing hardware, a representation of the one or more indicators of the small bowel injury; wherein the representation graphically represents the set of regions characterized by the medical data.

60. A method of identifying a marker of an enteropathy, or lack thereof, in the small bowel of a subject, the method comprising: receiving medical imaging data characterizing a set of regions of the small bowel of the subject, wherein the medical imaging data comprises a set of imaging frames; for each frame of the set of imaging frames, determining a score indicative of the injury state of the small bowel captured by the respective imaging frame; and generating a graphical representation for the set of regions of the small bowel characterized by the medical imaging data based on the score of each frame of the set of imaging frames.

61. The method of claim 60 further comprising displaying the graphical representation on a graphical user interface as a curve, wherein each coordinate on the curve corresponds to a respective generated score for a respective imaging frame at a relative position within the small bowel.

62. A method of identifying a marker of an enteropathy, or lack thereof, in a subject, the method comprising:(1) assessing one or more indicators of small bowel injury in the small bowel of the subject;(2) assigning an injury score for each of the one or more indicators of small bowel injury; and(3) generating a marker.

63. The method of claim 62, wherein the one or more indicators of small bowel injury are: a villous height / crypt depth (Vh:Cd) ratio; an enzyme-linked immunosorbent spot (ELISpot) assay; an IL-2 serology assay; a CD4 assay; a CD8 assay; an intraepithelial lymphocytes (IEL) count; a Marsh score; a patient-reported outcome assessment; or villous atrophy.

64. The method of claim 62, wherein the injury score comprises a level of injury corresponding to an ordinal scale.

65. The method of claim 64, wherein the level of injury ranges from 0-10, wherein 0 corresponds to no villous atrophy; and wherein 10 corresponds to complete villous atrophy; from 0-9, wherein 0 corresponds to no villous atrophy; and wherein 9 corresponds to complete villous atrophy; from 0-8, wherein 0 corresponds to no villous atrophy; and wherein 8 corresponds to complete villous atrophy; from 0-7, wherein 0 corresponds to no villous atrophy; and wherein 7 corresponds to complete villous atrophy; from 0-6, wherein 0 corresponds to no villous atrophy; and wherein 6 corresponds to complete villous atrophy; from 0-5, wherein 0 corresponds to no villous atrophy; and wherein 5 corresponds to complete villous atrophy; from 0-4, wherein 0 corresponds to no villous atrophy; and wherein 4 corresponds to complete villous atrophy; orfrom 0-3 wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy.

66. The method of claim 64, wherein the level of injury ranges from 0-10, wherein 0 corresponds to no villous atrophy; and wherein 10 corresponds to complete villous atrophy.

67. The method of claim 66, wherein the level of injury ranges from 0-3, wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy.

68. The method of claim 64-67, wherein the level of injury is determined via: a visual assessment; a level or amount of fluorescence; a level or amount of radioactivity; a microscopic examination; a histopathological assessment; an assessment of the average height of the villi relative to the average depth of the crypts in a biopsy sample; or an assessment of the number of lymphocytes relative to the number of enterocytes (intestinal epithelial cells).

69. The method of claim 68, wherein the visual assessment is of one or more image frames.

70. The method of claim 69, wherein the one or more image frames are: one or more photographic image frames; one or more sonographic image frames; one or more radiographic image frames; one or more confocal image frames; or one or more tomographic image frames.

71. The method of claim 70, wherein the one or more image frames is one or more photographic image frames.

72. The method of claim 71, wherein the one or more photographic image frames are one or more frames of a video.

73. The method of claim 72, wherein the injury score is determined for each of the one or more frames of the video.

74. The method of any one of claims 69-73, wherein the injury score is determined for each of the one or more images frames.

75. The method of claim 74, wherein the one or more images frames are at least two or more image frames.

76. The method of claim 75, wherein the at least two or more image frames are obtained circumferentially and / or proximodistally along the interior of the small bowel of the subject.

77. The method of any one of claims 62-76, wherein the marker is generated by determining:(a) a curve fit to the injury score for the entirety of the small bowel of the subject, and using equally spaced points therein; and(b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof.

78. The method of claim 77, wherein the marker is generated for:(a) the entire small bowel of the subject;(b) one or more regions of interest (ROI) of the small bowel of the subject; or(c) any combination thereof.

79. The method of claim 78, further comprising generating a graphical representation of the marker.

80. The method of claim 79, wherein the graphical representation is generated by data processing hardware.

81. The method of claim 80, further comprising displaying the graphical representation on a graphical user interface as a curve, wherein each coordinate on the curve corresponds to a respective injury score, for a respective region of interest at a relative position within the small bowel.

82. The method of any one of claims 62-81, wherein the marker is identified for:(a) the entire small bowel of:(i) a subject confirmed as not having an enteropathy;(ii) a plurality of subjects, wherein each subject of the plurality of subjects are independently confirmed as not having an enteropathy;(iii) a subject diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy;(iv) a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy; or(b) one or more regions of interest (ROI), comprising:(i) one or more ROI of the small bowel of a subject, wherein the subject is confirmed as not having an enteropathy in the one or more ROI;(ii) a plurality of one or more ROI of the small bowels of a plurality of subjects, wherein each subject of the plurality of subjects are independently confirmed as not having an enteropathy in the one or more ROIs;(iii) one or more ROI of the small bowel of a subject, wherein the subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy in the one or more ROI;(iv) a plurality of one or more ROI of the small bowels of a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy in the one or more ROI.

83. The method of any one of claims 62-82, wherein the marker is identified:(a) prior to treating or having treated the subject with a treatment for the enteropathy;(b) during the treatment of the subject for the enteropathy;(c) after treating the subject with the treatment for the enteropathy;(d) during at least two time points, wherein the two time points are selected from: one or more time points prior to the treatment of the subject, one or more time points during thetreatment of the subject, or one or more time points after the treatment of the subject, for the enteropathy; or(e) to establish one or more reference markers indicative of an enteropathy, or a lack thereof, in a subject diagnosed with or confirmed to have the enteropathy.

84. The method any one of claims 62-83, wherein the marker is indicative of one or more of:(i) an enteropathy, or a lack thereof, in the subject;(ii) a level of severity of an enteropathy;(iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or(iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

85. A method of identifying a marker of an enteropathy, or lack thereof, in a subject, the method comprising:(1) assessing villous atrophy in the small bowel of the subject;(2) assigning an injury score for each of the one or more indicators of small bowel injury; wherein the injury score comprises a level of injury determined via a visual assessment of one or more frames of a video; wherein the level of injury corresponds to an ordinal scale ranging from 0-3; wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy;(3) generating a marker by determining:(a) a curve fit to the injury score for the entirety of the small bowel of the subject, and using equally spaced points therein; and(b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; wherein the marker identified in Step (3) is indicative of one or more of:(i) an enteropathy, or a lack thereof, in the subject;(ii) a level of severity of an enteropathy;(iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or(iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

86. A method of recommending a treatment for an enteropathy in a subject in need thereof, the method comprising:(1) capturing one or more indicators of small bowel injury in the small bowel of the subject;(2) assigning an injury score for each of the one or more indicators of small bowel injury;(3) generating a summary score based on the injury score;(4) identifying a marker of an enteropathy, or lack thereof, based on the summary score; and(5) recommending a treatment for an enteropathy based on the marker identified in Step (4).

87. The method of claim 86, wherein the treatment is one or more of: a dietary recommendation, a behavior change, or a drug prescription.

88. The method of claim 87, wherein the one or more indicators of small bowel injury are: a villous height / crypt depth (Vh:Cd) ratio; an enzyme-linked immunosorbent spot (ELISpot) assay; an IL-2 serology assay; a CD4 assay; a CD8 assay; an intraepithelial lymphocytes (IEL) count; a Marsh score; a patient-reported outcome assessment; or villous atrophy.

89. The method of claim 87, wherein the injury score comprises a level of injury corresponding to an ordinal scale.

90. The method of claim 89, wherein the level of injury ranges from 0-10, wherein 0 corresponds to no villous atrophy; and wherein 10 corresponds to complete villous atrophy; from 0-9, wherein 0 corresponds to no villous atrophy; and wherein 9 corresponds to complete villous atrophy; from 0-8, wherein 0 corresponds to no villous atrophy; and wherein 8 corresponds to complete villous atrophy; from 0-7, wherein 0 corresponds to no villous atrophy; and wherein 7 corresponds to complete villous atrophy; from 0-6, wherein 0 corresponds to no villous atrophy; and wherein 6 corresponds to complete villous atrophy; from 0-5, wherein 0 corresponds to no villous atrophy; and wherein 5 corresponds to complete villous atrophy; from 0-4, wherein 0corresponds to no villous atrophy; and wherein 4 corresponds to complete villous atrophy; or from 0-3 wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy.

91. The method of claim 90, wherein the level of injury ranges from 0-10, wherein 0 corresponds to no villous atrophy; and wherein 10 corresponds to complete villous atrophy.

92. The method of claim 91, wherein the level of injury ranges from 0-3, wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy.

93. The method of claim 89-92, wherein the level of injury is determined via: a visual assessment; a level or amount of fluorescence; a level or amount of radioactivity; a microscopic examination; a histopathological assessment; an assessment of the average height of the villi relative to the average depth of the crypts in a biopsy sample; or an assessment of the number of lymphocytes relative to the number of enterocytes (intestinal epithelial cells).

94. The method of claim 93, wherein the visual assessment is of one or more image frames.

95. The method of claim 94, wherein the one or more image frames are: one or more photographic image frames; one or more sonographic image frames; one or more radiographic image frames; one or more confocal image frames; or one or more tomographic image frames.

96. The method of claim 95, wherein the one or more image frames is one or more photographic image frames.

97. The method of claim 96, wherein the one or more photographic image frames are one or more frames of a video.

98. The method of claim 97, wherein the injury score is determined for each of the one or more frames of the video.

99. The method of any one of claims 94-98, wherein the injury score is determined for each of the one or more images frames.

100. The method of claim 99, wherein the one or more images frames are at least two or more image frames.

101. The method of claim 100, wherein the at least two or more image frames are obtained circumferentially and / or proximodistally along the interior of the small bowel of the subject.

102. The method of any one of claims 86-101, wherein the summary score is generated by determining:(a) a curve fit to the injury score for the entirety of the small bowel of the subject, and using equally spaced points therein; and(b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof.

103. The method of any one of claims 86-102, wherein the marker of an enteropathy, or lack thereof, is identified by assigning the summary score to:(a) the entire small bowel of the subject;(b) one or more regions of interest (ROI) of the small bowel of the subject; or(c) any combination thereof.

104. The method of any one of claims 86-103, wherein the marker of an enteropathy, or lack thereof, is indicative of one or more of:(i) an enteropathy, or a lack thereof, in the subject;(ii) a level of severity of an enteropathy;(iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or(iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

105. The method of any one of claims 86-104, further comprising generating a graphical representation of the marker.

106. The method of claim 105, wherein the graphical representation is generated by data processing hardware.

107. The method of claim 106, further comprising displaying the graphical representation of the marker on a graphical user interface as a curve, wherein each coordinate on the curve corresponds to a respective injury score, for a respective region of interest at a relative position within the small bowel.

108. The method of any one of claims 86-107, further comprising comparing the marker identified in Step (4), or the graphical representation thereof, with one or more of the following:(i) a marker in a subject confirmed as not having an enteropathy, or a graphical representation thereof;(ii) markers obtained from a plurality of subjects, wherein each subject of the plurality of subjects are independently confirmed as not having an enteropathy, or graphical representations thereof;(iii) a marker in a subject diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy, or a graphical representation thereof;(iv) markers obtained from a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy; or graphical representations thereof.

109. The method of claim 108, wherein: if the marker identified in step (4), or the graphical representation thereof, is similar to: (iii) the marker in a subject diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy, or the graphical representation thereof; or(iv) the markers obtained from a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy; or the graphical representations thereof; then the marker identified in step (4), or the graphical representation thereof, is indicative of:(i) the presence of an enteropathy in the subject;(ii) the level of severity of the enteropathy in the subject;(iii) a likely therapeutic response in the subject to a treatment for the enteropathy; or(iv) a likely adverse response in the subject to a treatment for the enteropathy.

110. The method of any one of claims 108-109, wherein the comparison is determined by a user, or an Artificial Intelligence (Al) approach.

111. The method of any one of claims 86-110, wherein the recommendation of the treatment is communicated to a user.

112. A method of identifying a marker of an enteropathy, or lack thereof, in the small bowel of a subject, the method comprising:(1) capturing one or more indicators of small bowel injury in the small bowel of the subject;(2) assigning an injury score for each of the one or more indicators of small bowel injury;(3) generating a summary score based on the injury score; and(4) identifying the marker of an enteropathy by assigning the summary score generated in Step(3) to:(a) the entire small bowel of the subject;(b) one or more regions of interest (ROI) of the small bowel of the subject; or(c) any combination thereof.

113. The method of claim 112, wherein the one or more indicators of small bowel injury are: a villous height / crypt depth (Vh:Cd) ratio; an enzyme-linked immunosorbent spot (ELISpot)assay; an IL-2 serology assay; a CD4 assay; a CD8 assay; an intraepithelial lymphocytes (IEL) count; a Marsh score; a patient-reported outcome assessment; or villous atrophy.

114. The method of any one of claims 112-113, wherein the injury score comprises a level of injury corresponding to an ordinal scale.

115. The method of claim 114, wherein the level of injury ranges from 0-10, wherein 0 corresponds to no villous atrophy; and wherein 10 corresponds to complete villous atrophy; from 0-9, wherein 0 corresponds to no villous atrophy; and wherein 9 corresponds to complete villous atrophy; from 0-8, wherein 0 corresponds to no villous atrophy; and wherein 8 corresponds to complete villous atrophy; from 0-7, wherein 0 corresponds to no villous atrophy; and wherein 7 corresponds to complete villous atrophy; from 0-6, wherein 0 corresponds to no villous atrophy; and wherein 6 corresponds to complete villous atrophy; from 0-5, wherein 0 corresponds to no villous atrophy; and wherein 5 corresponds to complete villous atrophy; from 0-4, wherein 0 corresponds to no villous atrophy; and wherein 4 corresponds to complete villous atrophy; or from 0-3 wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy.

116. The method of claim 115, wherein the level of injury ranges from 0-10, wherein 0 corresponds to no villous atrophy; and wherein 10 corresponds to complete villous atrophy.

117. The method of claim 116, wherein the level of injury ranges from 0-3, wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy.

118. The method of claim 117, wherein 0 corresponds to no villous atrophy (no disease), 1 corresponds to mild villous atrophy (mild disease), 2 corresponds to moderate villous atrophy (moderate disease), and 3 corresponds to severe villous atrophy (severe disease).

119. The method of claim 114-118, wherein the level of injury is determined via: a visual assessment; a level or amount of fluorescence; a level or amount of radioactivity; a microscopic examination; a histopathological assessment; an assessment of the average height of the villirelative to the average depth of the crypts in a biopsy sample; or an assessment of the number of lymphocytes relative to the number of enterocytes (intestinal epithelial cells).

120. The method of claim 119, wherein the visual assessment is of one or more image frames.

121. The method of claim 120, wherein the one or more image frames are: one or more photographic image frames; one or more sonographic image frames; one or more radiographic image frames; one or more confocal image frames; or one or more tomographic image frames.

122. The method of claim 121, wherein the one or more image frames is one or more photographic image frames.

123. The method of claim 122, wherein the one or more photographic image frames are one or more frames of a video.

124. The method of claim 123, wherein the injury score is determined for each of the one or more frames of the video.

125. The method of any one of claims 120-124, wherein the injury score is determined for each of the one or more images frames.

126. The method of claim 125, wherein the one or more images frames are at least two or more image frames.

127. The method of claim 126, wherein the at least two or more image frames are obtained circumferentially and / or proximodistally along the interior of the small bowel of the subject.

128. The method of any one of claims 112-127 wherein the summary score is generated by calculating:(a) a curve fit to the injury score for each of the one or more frames of the video, for the entirety of the small bowel of the subject, and using equally spaced points therein; and(b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof.

129. The method any one of claims 112-128, wherein the marker of an enteropathy is indicative of one or more of:(i) an enteropathy, or a lack thereof, in the subject;(ii) a level of severity of an enteropathy;(iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or(iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

130. The method of any one of claims 112-129, wherein the marker of an enteropathy is identified for:(a) the entire small bowel of:(i) a subject confirmed as not having an enteropathy;(ii) a plurality of subjects, wherein each subject of the plurality of subjects are independently confirmed as not having an enteropathy;(iii) a subject diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy;(iv) a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy; or(b) one or more regions of interest (ROI), comprising:(i) one or more ROI of the small bowel of a subject, wherein the subject is confirmed as not having an enteropathy in the one or more ROI;(ii) a plurality of one or more ROI of the small bowels of a plurality of subjects, wherein each subject of the plurality of subjects are independently confirmed as not having an enteropathy in the one or more ROIs;(iii) one or more ROI of the small bowel of a subject, wherein the subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy in the one or more ROI;(iv) a plurality of one or more ROI of the small bowels of a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy in the one or more ROI.

131. The method of any one of claims 112-130, wherein the marker of an enteropathy is identified:(a) prior to treating or having treated the subject with a treatment for the enteropathy;(b) during the treatment of the subject for the enteropathy;(c) after treating the subject with the treatment for the enteropathy;(d) during at least two time points, wherein the two time points are selected from: one or more time points prior to the treatment of the subject, one or more time points during the treatment of the subject, or one or more time points after the treatment of the subject, for the enteropathy; or(e) to establish one or more reference markers indicative of an enteropathy, or a lack thereof, in a subject diagnosed with or confirmed to have the enteropathy.

132. A method of identifying a marker of an enteropathy, or lack thereof in the small bowel of a subject, the method comprising:(1) capturing one or more frames of a video of the small bowel of the subject;(2) determining a level of villous atrophy to each of the one or more frames of the video;(3) assigning an injury score for each of the one or more frames of the video, wherein the injury score comprises a level of injury intensity ranging from 0-3, wherein 0 is no villous atrophy; and wherein 3 is complete villous atrophy;(4) generating a summary score for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof, by calculating:(a) a curve fit to the injury score for each of the one or more frames of the video provided in Step (3), for the entirety of the small bowel of the subject, and using equally spaced points therein; and(b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and(5) identifying the marker by assigning the summary score generated in Step (4) to: (a) the entire small bowel of the subject; (b) one or more regions of interest (ROI) of the small bowel of the subject; or (c) any combination thereof; wherein the marker is indicative of one or more of:(i) an enteropathy, or a lack thereof, in the subject;(ii) a level of severity of an enteropathy;(iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or(iv) an actual therapeutic or adverse response to a treatment for an enteropathy.

133. The method claim 132, wherein the marker is identified for:(a) the entire small bowel of:(i) a subject confirmed as not having an enteropathy;(ii) a plurality of subjects, wherein each subject of the plurality of subjects are independently confirmed as not having an enteropathy;(iii) a subject diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy;(iv) a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy; or(b) one or more regions of interest (ROI), comprising:(i) one or more ROI of the small bowel of a subject, wherein the subject is confirmed as not having an enteropathy in the one or more ROI;(ii) a plurality of one or more ROI of the small bowels of a plurality of subjects, wherein each subject of the plurality of subjects are independently confirmed as not having an enteropathy in the one or more ROIs;(iii) one or more ROI of the small bowel of a subject, wherein the subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy in the one or more ROI;(iv) a plurality of one or more ROI of the small bowels of a plurality of subjects, wherein each subject of the plurality of subjects is independently diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, an enteropathy in the one or more ROI.

134. The method of any one of claims 132-133, wherein the marker of an enteropathy is identified:(a) prior to treating or having treated the subject or the plurality of subjects with a treatment for the enteropathy;(b) during the treatment of the subject or the plurality of subjects for the enteropathy;(c) after treating the subject or the plurality of subjects with the treatment for the enteropathy;(d) during at least two time points, wherein the two time points are selected from: one or more time points prior to the treatment of the subject or the plurality of subjects, one or more time points during the treatment of the subject or the plurality of subjects, or one or more time points after the treatment of the subject or the plurality of subjects, for the enteropathy; or(e) to establish one or more reference markers indicative of an enteropathy, or a lack thereof, in a subject or a plurality of subjects diagnosed with or confirmed to have the enteropathy.

135. The method of any one of claims 132-134, further comprising diagnosing or identifying an enteropathy in the subject, the method comprising:(1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, or a combination thereof;(a) wherein the one or more first reference markers comprise the summary score for:(i) the entire small bowel of a first reference subject, wherein the first reference subject is confirmed as not having the enteropathy;(ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is confirmed as not having the enteropathy in the one or more first reference ROI; or(iii) a combination thereof;(b) wherein the one or more second reference markers comprise the summary score for:(i) the entire small bowel of a second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy;(ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy in the one or more second reference ROI; or(iii) a combination thereof; and(c) wherein the one or more subject markers comprise the summary score for:(i) the entire small bowel of the subject;(ii) one or more subject ROI of the small bowel of the subject; or(iii) a combination thereof; and(2) comparing the at least two or more markers; wherein:(i) if the one or more subject marker summary scores are comparable to the one or more first reference markers summary score, then the subject is diagnosed as not having the enteropathy;(ii) if the one or more subject marker summary scores are comparable to the one or more second reference markers summary score, then the subject is diagnosed as having the enteropathy.

136. The method of any one of claims 132-134, further comprising determining a level of severity of an enteropathy, the method comprising:(1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, or a combination thereof;(a) wherein the one or more first reference markers comprise the summary score for:(i) the entire small bowel of a first reference subject, wherein the first reference subject is confirmed as not having the enteropathy;(ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is confirmed as not having the enteropathy in the one or more first reference ROI; or(iii) a combination thereof;(b) wherein the one or more second reference markers comprise the summary score for:(i) the entire small bowel of a second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy;(ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have, the enteropathy in the one or more second reference ROI; or(iii) a combination thereof; and(c) wherein the one or more subject markers comprise the summary score for:(i) the entire small bowel of the subject;(ii) one or more subject ROI of the small bowel of the subject; or(iii) a combination thereof; and(2) comparing the at least two or more markers; wherein:(i) if the one or more subject marker summary scores are comparable to or less than the one or more first reference markers summary scores, then the subject is determined to have a less severe enteropathy, relative to the level of severity of the enteropathy in the first reference subject; and(ii) if the one or more subject marker summary scores are comparable to or greater than the one or more second reference markers summary scores, then the subject is diagnosed as having a more severe enteropathy relative to the level of severity of the enteropathy in the second reference subject.

137. The method of any one of claims 132-134, further comprising identifying a biological response to one or more treatments for an enteropathy in a subject; wherein the biological response is: a likely therapeutic response to; a likely adverse response to; an actual therapeutic response to; or an actual adverse response to; the one or more treatments for the enteropathy; or an improvement to a level of severity, or lack thereof, of the enteropathy; wherein the improvement or lack thereof is determined spatially, temporally, or a combination thereof; the method comprising:(1) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof;(a) wherein the one or more first reference markers comprise the summary score for:(i) the entire small bowel of a first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the first reference subject has an actual therapeutic response to the one or more treatments in the entire small bowel;(ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the one or more treatments in the one or more first ROI; or(iii) a combination thereof; wherein the summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof;(b) wherein the one or more second reference markers comprise the summary score for:(i) the entire small bowel of a second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the second reference subject does not have an actual therapeutic response to the one or more treatments in the entire small bowel;(ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have enteropathy in the one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the one or more treatments in the one or more second ROI; or(iii) a combination thereof; wherein the summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; or(c) wherein the one or more third reference markers comprise the summary score for:(i) the entire small bowel of a third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the one or more treatments in the entire small bowel;(ii) one or more third reference ROI of the small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the one or more treatments in the one or more third ROI; or(iii) a combination thereof; wherein the summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and(d) wherein the one or more subject markers comprise the summary score for:(i) the entire small bowel of the subject;(ii) one or more subject ROI of the small bowel of the subject; or(iii) a combination thereof; and wherein the summary score is determined: prior to the one or more treatments; during the one or more treatments; after the one or more treatments; or a combination thereof; and(2) comparing the at least two or more markers; wherein: if the one or more subject marker summary scores determined prior to the one or more treatments are comparable to the one or more first reference marker summary scores of any one of (l)(a)(i)-(iii) determined prior to the one or more treatments, then the subject is identified as being likely to have an actual therapeutic response to the one or more treatments; wherein: if the one or more subject marker summary scores determined during or after the one or more treatments are comparable to the one or more first reference marker summary scores of any one of (l)(a)(i)-(iii) determined during or after the one or more treatments, then the subject is identified as having an actual therapeutic response to the one or more treatments; wherein: if the one or more subject marker summary scores determined prior to the one or more treatments are comparable to the one or more second reference marker summary scores of any one of (l)(b)(i)-(iii) determined prior to the one or more treatments, then the subject is identified as being likely to not have an actual therapeutic response to the one or more treatments; wherein: if the one or more subject marker summary scores determined during or after the one or more treatments are comparable to the one or more second reference marker summary scores of any one of ( 1 )(b)(i)-(iii) determined during or after the one or more treatments, then the subject is identified as not having an actual therapeutic response to the one or more treatments; wherein:if the one or more subject marker summary scores determined prior to the one or more treatments are comparable to the one or more third reference marker summary scores of any one of (l)(c)(i)-(iii) determined prior to the one or more treatments, then the subject is identified as being likely to have an actual adverse response to the one or more treatments; wherein: if the one or more subject marker summary scores determined during or after the one or more treatments are comparable to the one or more third reference marker summary scores of any one of (l)(c)(i)-(iii) determined during or after the one or more treatments, then the subject is identified as having an actual adverse response to the one or more treatments; or wherein: if the one or more subject marker summary scores determined prior and during the one or more treatments are comparable to either the: one or more first reference marker summary scores of any one of (l)(a)(i)- (iii), one or more second reference marker summary scores of any one of (l)(b)(i)-(iii), one or more third reference marker summary scores of any one of (l)(c)(i)-(iii), as determined prior and during the one or more treatments; then the subject is identified: as having an actual therapeutic response to the one or more treatments over time; not having an actual therapeutic response to the one or more treatments over time; or having actual adverse response to the one or more treatments over time; respectively.

138. The method of claim 137, wherein the one or more treatments comprise a single treatment.

139. The method of claim 137, wherein the one or more treatments comprise two or more treatments.

140. The method of claim 138, wherein the biological response is identified for each of the two or more treatments independently.

141. The method of claim 140, wherein the biological response is identified for each of the two or more treatments independently by comparing the markers between: a subject receiving a first of the two or more treatments, a subject receiving a second of the two or more treatments, or a subject receiving both of the two or more treatments.

142. The method of claim 137, wherein the improvement to the level of severity, or lack thereof, is determined spatially by comparing at least two or more markers for: at least two or more different ROI in the same subject; or the same of one or more ROI obtained from two different subjects.

143. The method of claim 137, wherein the improvement to the level of severity, or lack thereof, is determined temporally by comparing at least two or more markers for: the entire small bowel of the subject at a first time, and one or more subsequent times; or one or more regions of interest (ROI) of the small bowel of the subject at a first time, and one or more subsequent times.

144. The method of any one of claims 132-134, further comprising identifying one or more treatments for an enteropathy, in a subject in need thereof, comprising:(1) identifying one or more treatments, wherein the one or more treatments comprise at least one candidate treatment;(2) treating or having treated at least one or more of: a first reference subject, a second reference subject, and a third reference subject with the at least one candidate treatments;(3) identifying at least two or more markers, wherein the at least two or more markers comprise at least two different markers selected from: one or more subject markers; and one or more first reference markers, one or more second reference markers, one or more third reference markers, or a combination thereof;(a) wherein the one or more first reference markers comprise the summary score for:(i) the entire small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the entire small bowel;(ii) one or more first reference ROI of the small bowel of the first reference subject, wherein the first reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more first reference ROI; wherein the first reference subject has an actual therapeutic response to the at least one candidate treatment in the one or more first ROI; or(iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof;(b) wherein the one or more second reference markers comprise the summary score for:(i) the entire small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; and wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the entire small bowel;(ii) one or more second reference ROI of the small bowel of the second reference subject, wherein the second reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more second reference ROI; wherein the second reference subject does not have an actual therapeutic response to the at least one candidate treatment in the one or more second ROI; or(iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof;(c) wherein the one or more third reference markers comprise the summary score for:(i) the entire small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the entire small bowel;(ii) one or more third reference ROI of the small bowel of the third reference subject, wherein the third reference subject is diagnosed with, is suspected of having, is displaying symptoms of, or is confirmed to have the enteropathy in the one or more third reference ROI; wherein the third reference subject has an actual adverse response to the at least one candidate treatment in the one or more third ROI; or(iii) a combination thereof; wherein the summary score is determined: prior to the at least one candidate treatment; during the at least one candidate treatment; after the at least one candidate treatment; or a combination thereof; and(d) wherein the one or more subject markers comprise the summary score for:(i) the entire small bowel of the subject;(ii) one or more subject ROI of the small bowel of the subject; or(iii) a combination thereof; and wherein the summary score is determined: prior to the at least one candidate treatment, or during the at least one candidate treatment; and(4) comparing the at least two or more markers, wherein: if the one or more subject marker summary scores determined prior to the at least one candidate treatment are comparable to the one or more first reference marker summary scores of any one of (a)(i)-(iii) determined prior to the at least one candidate treatment, then the at least one candidate treatment is identified as being likely to have an actual therapeutic response in the subject; wherein:if the one or more subject marker summary scores determined during the at least one candidate treatment are comparable to the one or more first reference marker summary scores of any one of (a)(i)-(iii) determined during the at least one candidate treatment, then the at least one candidate treatment is identified as having an actual therapeutic response in the subject; wherein: if the one or more subject marker summary scores determined prior to the at least one candidate treatment are comparable to the one or more second reference marker summary scores of any one of (b)(i)-(iii) determined prior to the at least one candidate treatment, then the at least one candidate treatment is identified as being likely to not have an actual therapeutic response in the subject; wherein: if the one or more subject marker summary scores determined during the at least one candidate treatment are comparable to the one or more second reference marker summary scores of any one of (b)(i)-(iii) determined during the at least one candidate treatment, then the at least one candidate treatment is identified as not having an actual therapeutic response in the subject; wherein: if the one or more subject marker summary scores determined prior to the at least one candidate treatment are comparable to the one or more third reference marker summary scores of any one of (c)(i)-(iii) determined prior to the at least one candidate treatment, then the at least one candidate treatment is identified as being likely to have an actual adverse response in the subject; wherein: if the one or more subject marker summary scores determined during the at least one candidate treatment are comparable to the one or more third reference marker summary scores of any one of (c)(i)-(iii) determined during the at least one candidate treatment, then the at least one candidate treatment is identified as having an actual adverse response in the subject; or wherein:if the one or more subject marker summary scores determined prior and during the at least one candidate treatment are comparable to either the: one or more first reference marker summary scores of any one of (a)(i)- (iii), one or more second reference marker summary scores of any one of (b)(i)- (iii), one or more third reference marker summary scores of any one of (c)(i)- (iii), as determined prior and during at least one candidate treatment; then the at least one candidate treatment is identified: as having an actual therapeutic response in the subject over time; not having an actual therapeutic response in the subject over time; or having actual adverse response in the subject over time; respectively.

145. The method of any one of claims 132-134, further comprising: administering a therapeutically effective amount of a treatment to a subject in need thereof, wherein the subject in need thereof has one or more markers indicative of one or more of:(a) an enteropathy;(b) a more severe level of an enteropathy in the subject in need thereof; relative to a level of severity of the enteropathy in a subject that does not have the enteropathy;(c) a likely therapeutic response of the subject in need thereof to a treatment for an enteropathy; or(d) an actual therapeutic response of the subject in need thereof to a treatment for an enteropathy; wherein the administration of the therapeutically effective amount of the treatment, to the subject in need thereof, results in a reduction in the occurrence or severity of the enteropathy, or a reduction of a symptom or pain associated thereof, relative to the occurrence or severity of the enteropathy, or a level of a symptom or pain associated thereof, in the subject prior to being administered the therapeutically effective amount of the treatment.

146. The method of any one of claims 132-134, wherein the marker is used to screen one or more subjects in a clinical trial.

147. The method of any one of claims 132-146, wherein the one or more regions of interest (ROI) comprise: a first or proximal tertile: a second or midline tertile; and a third or distal tertile.

148. The method of any one of claims 132-147, wherein the one or more frames of the video of the small bowel of the subject are captured using Video-Capsule Endoscopy (VCE).

149. The method of any one of claims 132-148, wherein the injury score is determined using a Celiac Enteropathy Villous Atrophy Scale (CE-VAST) score.

150. The method of any one of claims 132-149, wherein the summary score is generated using a Mucosal AtRophy Celiac Scale (MARCS) score.

151. The method of any one of claims 132-150, wherein the injury score or the summary score is determined by an Artificial Intelligence (Al) approach.

152. The method of claim 151, wherein the Al approach is supervised machine learning (ML).

153. The method of claim 152, wherein the supervised ML comprises a supervised deep learning algorithm operable to regress the injury score or the summary score directly from frames of the video.

154. The method of any one of claims 14-153, wherein the enteropathy is an immune disease.

155. The method of any one of claims 14-153, wherein the enteropathy a villous injury.

156. The method of any one of claims 14-153, wherein the enteropathy is inflammation.

157. The method of any one of claims 14-153, wherein the enteropathy is Celiac disease (CeD).

158. A method of identifying a marker of an enteropathy, or lack thereof, in the small bowel of a subject, the method comprising:(1) capturing one or more frames of a video of the small bowel of the subject using Video-Capsule Endoscopy (VCE);(2) determining a Celiac Enteropathy Villous Atrophy Scale (CE-VAST) score for each of the one or more frames of the video, wherein the CE-VAST score comprises a level of injury intensity ranging from 0-3, wherein 0 is no visual villous atrophy; and wherein 3 is complete visual villous atrophy;(3) generating a marker for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof, by calculating:(a) a curve fit to the CE-VAST score for each of the one or more frames of the video provided in Step (2), for the entirety of the small bowel of the subject, and using equally spaced points therein; and(b) a mean CE-VAST score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and wherein the marker is indicative of one or more of:(i) Celiac disease (CeD), or a lack thereof;(ii) a level of severity of Celiac disease (CeD) for the entirety of the small bowel, or one or more ROI therein;(iii) a likely therapeutic or adverse response of a treatment for Celiac disease (CeD) for the entirety of the small bowel, or one or more ROI therein, in a subject in need thereof; or(iv) an actual therapeutic or adverse response of a treatment for Celiac disease (CeD) for the entirety of the small bowel, or one or more ROI therein, in a subject in need thereof.

159. The method of claim 158, wherein the CE-VAST score is determined by supervised machine learning (ML).

160. The method of claim 159, wherein the MARCS score is generated by supervised machine learning (ML).

161. The method of any one of claims 158-160, wherein the supervised ML comprises a supervised deep learning algorithm operable to regress the CE-VAST score or the MARCS score directly from frames of the video.

162. A method of identifying a marker of an enteropathy, or lack thereof, in the small bowel of a subject, the method comprising:(1) capturing one or more frames of a video of the small bowel of the subject;(2) determining an injury score for each of the one or more frames of the video, wherein the injury score comprises a level of injury intensity ranging from 0-3, wherein 0 is no visual villous atrophy; and wherein 3 is complete visual villous atrophy;(3) generating a marker for: the entire small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof, by calculating:(a) a curve fit to the injury score for each of the one or more frames of the video provided in Step (2), for the entirety of the small bowel of the subject, and using equally spaced points therein; and(b) a mean injury score, and a maximum point along the curve, for the entirety of the small bowel of the subject; one or more regions of interest (ROI) of the small bowel of the subject; or a combination thereof; and wherein the marker is indicative of one or more of:(i) Celiac disease (CeD), or a lack thereof;(ii) a level of severity of Celiac disease (CeD) for the entirety of the small bowel, or one or more ROI therein;(iii) a likely therapeutic or adverse response of a treatment for Celiac disease (CeD) for the entirety of the small bowel, or one or more ROI therein, in a subject in need thereof; or(iv) an actual therapeutic or adverse response of a treatment for Celiac disease (CeD) for the entirety of the small bowel, or one or more ROI therein, in a subject in need thereof.

163. The method of claim 158, wherein the injury score is determined by supervised machine learning (ML).

164. The method of claim 159, wherein the marker is generated by supervised machine learning (ML).

165. The method of any one of claims 162-164, wherein the supervised ML comprises a supervised deep learning algorithm operable to regress the injury score or the marker directly from frames of the video.

166. A computer-implemented method comprising: receiving an indication of a selection corresponding to a coordinate on a curve of a plot representing a quantitative metric that characterizes a region of an internal cavity of an organ associated with a subject, wherein the coordinate includes a first number indicating a position in the internal cavity, and wherein the coordinate further includes a second number indicating a value for the quantitative metric indicated by the first number; in response to the received indication: determining an image captured to represent a portion of the internal cavity of the organ associated with the subject, wherein the image corresponds to the position indicated by the first number; and displaying, at a graphical user interface: the coordinate comprising the first number and the second number on the curve of the plot in a first viewing window of the graphical user interface; and the determined image indicated by the selection in a second viewing window of the graphical user interface.

167. The method of claim 166, wherein the image is associated with a set of images from an endoscopy of the subject.

168. The method of claim 166, wherein the image is captured by a video capsule.

169. The method of claim 168, wherein the video capsule has at least a 170 degree field of view.

170. The method of claim 168, wherein the video capsule is capable of a 360 degree field of view.

171. The method of claim 166, wherein displaying the coordinate and the image further comprises simultaneously displaying the coordinate and the image at the graphical user interface such that the coordinate and the image are observable by a user of the graphical user interface at the same time.

172. The method of any one of claims 166-171, wherein: the curve corresponds to a set of discrete values for an area of interest for the internal cavity of the organ; and each discrete value in the set of discrete values characterizes a state of a portion of the internal cavity of the organ within the area of interest captured by a respective image from a set of images comprising the first image as indicated by the selection according to the quantitative metric.

173. The method of claim 172, wherein each discrete value in the set of discrete values represents an injury score, wherein the injury score comprises a level of injury corresponding to an ordinal scale.

174. The method of claim 173, wherein the level of injury ranges from 0-10, wherein 0 corresponds to no villous atrophy; and wherein 10 corresponds to complete villous atrophy; from 0-9, wherein 0 corresponds to no villous atrophy; and wherein 9 corresponds to complete villousatrophy; from 0-8, wherein 0 corresponds to no villous atrophy; and wherein 8 corresponds to complete villous atrophy; from 0-7, wherein 0 corresponds to no villous atrophy; and wherein 7 corresponds to complete villous atrophy; from 0-6, wherein 0 corresponds to no villous atrophy; and wherein 6 corresponds to complete villous atrophy; from 0-5, wherein 0 corresponds to no villous atrophy; and wherein 5 corresponds to complete villous atrophy; from 0-4, wherein 0 corresponds to no villous atrophy; and wherein 4 corresponds to complete villous atrophy; or from 0-3 wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy.

175. The method of claim 173, wherein the level of injury ranges from 0-10, wherein 0 corresponds to no villous atrophy; and wherein 10 corresponds to complete villous atrophy.

176. The method of claim 175, wherein the level of injury ranges from 0-3, wherein 0 corresponds to no villous atrophy; and wherein 3 corresponds to complete villous atrophy.

177. The method of any one of claims 166-176, wherein the curve is indicative of one or more of:(i) an enteropathy, or a lack thereof, in the subject;(ii) a level of severity of an enteropathy;(iii) a likely therapeutic or adverse response to a treatment for an enteropathy; or(iv) an actual therapeutic or adverse response to a treatment for an enteropathy

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