Compositions and methods for IBD patients using stool-derived eukaryotic nucleic acids
Stool-derived eukaryotic nucleic acid biomarkers enhance IBD diagnosis and treatment by improving diagnostic accuracy and predicting treatment responses, addressing the limitations of existing methods.
Patent Information
- Application Number
- JP2025544353
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-10-19
- Filing Date
- 2024-01-30
- Publication Date
- 2026-01-28
AI Technical Summary
Current noninvasive diagnostic methods for inflammatory bowel disease (IBD) lack sensitivity and specificity, making it difficult for physicians to accurately diagnose, monitor inflammation, and predict treatment responses in IBD patients.
Utilizing stool-derived eukaryotic nucleic acid biomarkers, particularly RNA, for diagnosing IBD, assessing disease activity, and predicting treatment responses through methods that extract high-quality nucleic acids and proteins from stool samples.
Provides accurate diagnostic and predictive tools for IBD, allowing better management and treatment of the disease by measuring expression levels of specific biomarkers in stool samples.
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Figure 2026503318000001_ABST
Abstract
Description
[Technical Field]
[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent Application No. 63 / 441,973, filed January 30, 2023, and also U.S. Provisional Patent Application No. 63 / 544,876, filed October 19, 2023, the entire disclosures of both of which are incorporated herein by reference. [Background technology]
[0002] Inflammatory bowel disease (IBD) is a group of difficult-to-manage diseases, including ulcerative colitis (UC) and Crohn's disease (CD). IBD affects more than 3 million people in the United States, with an annual economic burden exceeding $6.3 billion. IBD typically requires a combination of multiple tests to make an initial diagnosis, and effective treatment can take many months. The goal of treatment is generally to maintain long-term remission to effectively avoid complications, surgery, malignancies, and iatrogenic side effects. Currently, methods for diagnosing, monitoring, and evaluating treatment effectiveness in IBD patients primarily involve invasive tests, such as colonoscopy and sigmoidoscopy, which require inconvenient and uncomfortable bowel preparation. [Prior art documents] [Patent documents]
[0003] [Patent Document 1] WO No. 2018 / 081580 [Patent Document 2] WO No. 2019 / 232483 Summary of the Invention [Problem to be solved by the invention]
[0004] Existing noninvasive diagnostic methods for IBD fall into three categories: blood-based protein biomarkers, stool-based protein biomarkers, or stool-based microbiome biomarkers. Serological markers include Saccharomyces cerevisiae mannan antibodies, perinuclear antineutrophil cytoplasmic antibodies, and IgA / IgG antibodies. Fecal markers include calprotectin, lactoferrin, and lymphocyte markers. Stool-based microbiome biomarkers continue to be investigated, although definitive studies are not currently available. However, the current intended use, sensitivity, and specificity of these noninvasive diagnostic tests are insufficient to assist physicians in accurately diagnosing patients in a timely manner, monitoring inflammation and mucosal healing during treatment, and predicting response to therapeutics. Therefore, there is a need for new compositions and methods to provide clinicians with predictive and clinical biomarkers for IBD. [Means for solving the problem]
[0005] Thus, the present disclosure provides compositions and methods for using stool-derived eukaryotic nucleic acid biomarkers to diagnose disease, assess disease activity, monitor mucosal healing, and predict treatment response. Ultimately, the biomarkers of the present invention can be used by physicians to better diagnose, manage, and treat IBD.
[0006] The compositions and methods of the present disclosure offer several advantages over the current prior art. For example, the present disclosure utilizes extraction methods that allow for the isolation of high-quality eukaryotic nucleic acids (e.g., DNA and / or RNA) and proteins (e.g., calprotectin) from stool samples. Methods that can be used in accordance with the present disclosure are described in PCT International Application Publication No. WO 2018 / 081580 and also PCT International Application Publication No. WO 2019 / 232483, both of which are incorporated herein by reference in their entireties. By way of example, stool-derived eukaryotic RNA (seRNA) is provided herein for identifying eukaryotic RNA preserved during the process of fecal material production, which can then be extracted from stool samples by the methods described herein.
[0007] Other objects, features, and advantages of the present disclosure will become apparent from the following detailed description of the invention. It should be understood, however, that this detailed description and the specific examples, while indicating particular embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.
[0008] In the detailed description, particular reference is made to the accompanying drawings, in which: [Brief explanation of the drawings]
[0009] [Figure 1] 1A-1B show the seRNA classifier for approximate disease activity for remission versus active disease (FIG. 1A) and disease severity for distinguishing mild versus moderate disease (FIG. 1B). [Figure 2] Figures 2A-2C show seRNA biomarkers that can be used to predict response to targeted therapeutics, as demonstrated by longitudinal seRNA assessment of 16 subjects treated with targeted therapies. Figure 2A shows subjects treated with vedolizumab, Figure 2B shows subjects treated with ustekinumab, and Figure 2C shows subjects treated with infliximab. [Figure 3]FIG. 1 shows protein-based calprotectin measurements (ELISA assay) compared to RNA-based calprotectin measurements (whole transcriptome sequencing). [Figure 4] FIG. 1 shows receiver operating characteristics (ROC) comparing protein-based and RNA-based methods for calprotectin. DETAILED DESCRIPTION OF THE INVENTION
[0010] Detailed Description Various embodiments of the present invention are described herein below. In an exemplary aspect, a method for assessing disease in a subject is provided. The method comprises measuring the expression level of one or more stool-derived eukaryotic nucleic acid biomarkers selected from the biomarkers described herein in eukaryotic nucleic acid extracted from a stool sample from the subject, wherein the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample indicates the assessment of disease in the subject.
[0011] In certain embodiments, the method comprises comparing the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample with the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in a control, wherein a difference in the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample relative to the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the control indicates an assessment of disease in the subject.
[0012] In some embodiments, the nucleic acid is DNA. In some embodiments, the nucleic acid is RNA. In some embodiments, the nucleic acid is a combination of DNA and RNA.
[0013] In some embodiments, the disease is inflammatory bowel disease (IBD). In some embodiments, the disease is ulcerative colitis (UC). In some embodiments, the disease is Crohn's disease (CD).
[0014] In some embodiments, assessing the disease includes assessing disease activity in the subject. In some embodiments, the assessment is determining active IBD symptoms in the subject. In some embodiments, the determination of active IBD symptoms indicates mild IBD symptoms. In some embodiments, the determination of active IBD symptoms indicates moderate IBD symptoms. In some embodiments, the determination of active IBD symptoms indicates severe IBD symptoms. In some embodiments, the assessment is determining IBD remission in the subject.
[0015] The present disclosure includes a variety of stool-derived eukaryotic nucleic acid biomarkers. Certain stool-derived eukaryotic nucleic acid biomarkers are presented in Tables 1-5 of the present disclosure. As described herein, a stool-derived eukaryotic nucleic acid biomarker can be selected from one of the groups of biomarkers in these tables, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29. The nucleic acids of the invention may comprise the nucleotide sequence of any one of the stool-derived eukaryotic nucleic acid biomarkers listed in Table 1 or Table 2 or Table 3 or Table 4, or a combination of Table 1 and Table 2 or Table 3 or Table 4, or a combination presented in Table 5, or any one of the stool-derived eukaryotic nucleic acid biomarkers listed in Table 1 or Table 2 or Table 3 or Table 4, or a combination of Table 1 and Table 2 or Table 3 or Table 4, or a combination presented in Table The combinations may include nucleic acids having a nucleic acid sequence that is at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% identical to the nucleic acid sequences of the combinations presented in Table 5.
[0016] A group of biomarkers from one of the tables can be derived based on one or more parameters, such as IBD disease severity (e.g., mild, moderate, active, remission) and patient response. Additionally, a group of biomarkers can be derived based on frequency, error rate, and / or possible combinations.
[0017] In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 1. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 2. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 3. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 4. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include a combination of biomarkers listed in Table 5.
[0018] [Table 1A]
[0019] [Table 1B]
[0020] [Table 1C]
[0021] [Table 2]
[0022] [Table 3A]
[0023] [Table 3B]
[0024] [Table 3C]
[0025] [Table 4]
[0026] [Table 5]
[0027] In some embodiments, the one or more stool-derived eukaryotic nucleic acid biomarkers comprise stool-derived eukaryotic RNA biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise intestinal cell-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist essentially of intestinal cell-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist of intestinal cell-specific biomarkers.
[0028] In some embodiments, the stool-derived eukaryotic RNA biomarkers include inflammatory or inflammation-related biomarkers, such as lymphocyte-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist essentially of lymphocyte-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist of lymphocyte-specific biomarkers.
[0029] In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise a gut cell-specific biomarker and a lymphocyte-specific biomarker. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist essentially of a gut cell-specific biomarker and a lymphocyte-specific biomarker. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist of a gut cell-specific biomarker and a lymphocyte-specific biomarker.
[0030] In some embodiments, the stool-derived eukaryotic RNA biomarkers include one or more non-therapeutic targets, hi some embodiments, the one or more non-therapeutic targets are selected from the group consisting of RNA transcripts that mediate cytoskeletal remodeling, proliferation, and inflammatory responses.
[0031] In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise one or more therapeutic targets. In some embodiments, the one or more therapeutic targets are selected from the group consisting of TNF, MADCAM1, ITGA4, JAK1, TYK2, IL-12, IL-23, and any combination thereof. In some embodiments, the therapeutic target is TNF. In some embodiments, the therapeutic target is MADCAM1. In some embodiments, the therapeutic target is ITGA4. In some embodiments, the therapeutic target is JAK1. In some embodiments, the therapeutic target is TYK2. In some embodiments, the therapeutic target is IL-12. In some embodiments, the therapeutic target is IL-23.
[0032] In some embodiments, the one or more therapeutic targets are selected from the group consisting of a4B7, CCR6, CD30 ligand, FPR1, GLP-2, IL-2, IL-4 / IL-13, IL7R, IL-10, IL-12 / IL-23, IL-36, JAK, JAK1, JAK(ITK / TXK / JAK3), JAK3 / TEC, MC1r, MRP2, NLRP3 inflammasome, NLRX1, PDE4, PSGL-1, RIPK1, S1P1, TL1A, TLR9, TNFα, TNFSF15, TPL2, TREM1, TYK2, and any combination thereof. In some embodiments, the therapeutic target is a4B7. In some embodiments, the therapeutic target is CCR6. In some embodiments, the therapeutic target is CD30 ligand. In some embodiments, the therapeutic target is FPR1. In some embodiments, the therapeutic target is GLP-2. In some embodiments, the therapeutic target is IL-2. In some embodiments, the therapeutic target is IL-4 / IL-13. In some embodiments, the therapeutic target is IL7R. In some embodiments, the therapeutic target is IL-10. In some embodiments, the therapeutic target is IL-12 / IL-23. In some embodiments, the therapeutic target is IL-36. In some embodiments, the therapeutic target is JAK. In some embodiments, the therapeutic target is JAK1. In some embodiments, the therapeutic target is JAK (ITK / TXK / JAK3). In some embodiments, the therapeutic target is JAK3 / TEC. In some embodiments, the therapeutic target is MC1r. In some embodiments, the therapeutic target is MRP2. In some embodiments, the therapeutic target is the NLRP3 inflammasome. In some embodiments, the therapeutic target is NLRX1. In some embodiments, the therapeutic target is PDE4. In some embodiments, the therapeutic target is PSGL-1. In some embodiments, the therapeutic target is RIPK1. In some embodiments, the therapeutic target is S1P1. In some embodiments, the therapeutic target is TL1A. In some embodiments, the therapeutic target is TLR9. In some embodiments, the therapeutic target is TNFα. In some embodiments, the therapeutic target is TNFSF15. In some embodiments, the therapeutic target is TPL2. In some embodiments, the therapeutic target is TREM1. In some embodiments, the therapeutic target is TYK2.
[0033] In some embodiments, the evaluation comprises monitoring mucosal lesions in the subject. In some embodiments, the evaluation comprises evaluating inflammation in the subject. In some embodiments, the evaluation of inflammation comprises analyzing the amount of inflammation. In some embodiments, the evaluation of inflammation comprises analyzing the increase or decrease of inflammation. In some embodiments, the evaluation of inflammation comprises analyzing changes in inflammation.
[0034] In some embodiments, the evaluation includes evaluating a cell type in the subject. In some embodiments, the evaluation includes analyzing the amount of a cell type. In some embodiments, the evaluation includes analyzing the increase or decrease of a cell type. In some embodiments, the evaluation includes analyzing changes in the relative proportion of a cell type. In some embodiments, the cell type is an inflammatory cell. In some embodiments, the cell type is an immunogenic cell. In some embodiments, the cell type is an enterocyte. In some embodiments, the cell type is an enterocyte-associated cell. In some embodiments, the cell type is a lymphocyte cell. In some embodiments, the cell type is a lymphocyte-associated cell. In some embodiments, the cell type is a T cell. In some embodiments, the cell type is an NK cell. In some embodiments, the cell type is a B cell. In some embodiments, the cell type is a macrophage. In some embodiments, the cell type is a neutrophil. In some embodiments, the cell type is an endothelial cell. In some embodiments, the cell type is a fibroblast.
[0035] In some embodiments, the assessment is a prognosis of a therapeutic response to a medical intervention in a subject. In some embodiments, the medical intervention is a medication. In some embodiments, the medication is an IBD medication. In some embodiments, the medication is a UC medication. In some embodiments, the medication is a CD medication. In some embodiments, the medication comprises an anti-inflammatory drug. In some embodiments, the medication comprises an immune system suppressant. In some embodiments, the medication comprises a biologic. In some embodiments, the medication comprises an antibiotic. The medical therapy can include, for example, adalimumab (Humira) or ustekinumab (Stelara) or vedolizumab (Entyvio) or infliximab (Remicade) or tofacitinib (Xeljanz) or certolizumab (Cimzia) or golimumab (Simponi) or natalizumab (Tysabri) or ozanimod (Zeposia) or risankizumab-rzaa (Skyrizi) or upadacitinib (Rinvoq) or etrasimod (Velsipity) or mirikizumab or guselkumab or filgotinib. In one embodiment, the medical intervention is a colonoscopy.
[0036] In some embodiments, the evaluation is a determination of the therapeutic effectiveness of a medical intervention in a subject. In some embodiments, the medical intervention is a medication. In some embodiments, the medication is an IBD medication. In some embodiments, the medication is a UC medication. In some embodiments, the medication is a CD medication. In some embodiments, the medication comprises an anti-inflammatory drug. In some embodiments, the medication comprises an immune system suppressant. In some embodiments, the medication comprises a biologic. In some embodiments, the medication comprises an antibiotic. In some embodiments, the medical intervention is a colonoscopy. The medication may include, for example, adalimumab (Humira) or ustekinumab (Stelara) or vedolizumab (Entyvio) or infliximab (Remicade) or tofacitinib (Xeljanz) or certolizumab (Cimzia) or golimumab (Simponi) or natalizumab (Tysabri) or ozanimod (Zeposia) or risankizumab-rzaa (Skyrizi) or upadacitinib (Rinvoq) or etrasimod (Velspity) or mirikizumab or guselkumab or filgotinib.
[0037] In some embodiments, measuring the expression level of a nucleic acid biomarker comprises extracting nucleic acid from a eukaryotic cell. In some embodiments, measuring the expression level of a nucleic acid biomarker comprises extracting DNA from a eukaryotic cell. In some embodiments, measuring the expression level of a nucleic acid biomarker comprises extracting RNA from a eukaryotic cell. In some embodiments, measuring the expression level of a nucleic acid biomarker comprises next-generation sequencing.
[0038] In some embodiments, the method further comprises diagnosing the disease in the subject. In some embodiments, the disease is inflammatory bowel disease (IBD). In some embodiments, the disease is ulcerative colitis (UC). In some embodiments, the disease is Crohn's disease (CD).
[0039] In some embodiments, the method further comprises treating a disease in the subject. In some embodiments, the disease is inflammatory bowel disease (IBD). In some embodiments, the disease is ulcerative colitis (UC). In some embodiments, the disease is Crohn's disease (CD).
[0040] In some embodiments, treating the disease comprises administering to the subject an IBD medication. In some embodiments, treating the disease comprises administering to the subject a UC medication. In some embodiments, treating the disease comprises administering to the subject a CD medication. In some embodiments, treating the disease comprises administering to the subject an anti-inflammatory drug. In some embodiments, treating the disease comprises administering to the subject an immune system suppressant. In some embodiments, treating the disease comprises administering to the subject a biologic. In some embodiments, treating the disease comprises administering to the subject an antibiotic. Immune system suppressants can include, for example, adalimumab (Humira) or ustekinumab (Stelara) or vedolizumab (Entyvio) or infliximab (Remicade) or tofacitinib (Xeljanz) or certolizumab (Cimzia) or golimumab (Simponi) or natalizumab (Tysabri) or ozanimod (Zeposia) or risankizumab-rzaa (Skyrizi) or upadacitinib (Rinvoq) or etrasimod (Velspity) or mirikizumab or guselkumab or filgotinib.
[0041] In an exemplary embodiment, a method for predicting a therapeutic response to a disease in a subject is provided, the method comprising measuring the expression level of one or more stool-derived eukaryotic nucleic acid biomarkers selected from the biomarkers described herein in eukaryotic nucleic acid extracted from a stool sample from the subject, wherein the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample is indicative of a therapeutic response to the disease in the subject.
[0042] In certain embodiments, the method comprises comparing the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample with the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in a control, wherein a difference in the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample relative to the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the control indicates a treatment response to the disease in the subject.
[0043] In some embodiments, the nucleic acid is DNA. In some embodiments, the nucleic acid is RNA. In some embodiments, the nucleic acid is a combination of DNA and RNA. In some embodiments, the disease is inflammatory bowel disease (IBD). In some embodiments, the disease is ulcerative colitis (UC). In some embodiments, the disease is Crohn's disease (CD).
[0044] In some embodiments, the therapeutic response comprises assessing disease activity in the subject. In some embodiments, the assessment is determining active IBD symptoms in the subject. In some embodiments, the determination of active IBD symptoms indicates mild IBD symptoms. In some embodiments, the determination of active IBD symptoms indicates moderate IBD symptoms. In some embodiments, the determination of active IBD symptoms indicates severe IBD symptoms. In some embodiments, the assessment is determining IBD remission in the subject.
[0045] In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 1. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 2. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 3. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 4. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include a combination of biomarkers listed in Table 5.
[0046] In some embodiments, the one or more stool-derived eukaryotic nucleic acid biomarkers comprise stool-derived eukaryotic RNA biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise intestinal cell-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist essentially of intestinal cell-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist of intestinal cell-specific biomarkers.
[0047] In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise lymphocyte-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist essentially of lymphocyte-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist of lymphocyte-specific biomarkers.
[0048] In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise a gut cell-specific biomarker and a lymphocyte-specific biomarker. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist essentially of a gut cell-specific biomarker and a lymphocyte-specific biomarker. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist of a gut cell-specific biomarker and a lymphocyte-specific biomarker.
[0049] In some embodiments, the stool-derived eukaryotic RNA biomarkers include one or more non-therapeutic targets, hi some embodiments, the one or more non-therapeutic targets are selected from the group consisting of RNA transcripts that mediate cytoskeletal remodeling, proliferation, and inflammatory responses.
[0050] In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise one or more therapeutic targets. In some embodiments, the one or more therapeutic targets are selected from the group consisting of a4B7, CCR6, CD30 ligand, FPR1, GLP-2, IL-2, IL-4 / IL-13, IL7R, IL-10, IL-12 / IL-23, IL-36, JAK, JAK1, JAK(ITK / TXK / JAK3), JAK3 / TEC, MC1r, MRP2, NLRP3 inflammasome, NLRX1, PDE4, PSGL-1, RIPK1, S1P1, TL1A, TLR9, TNFα, TNFSF15, TPL2, TREM1, TYK2, and any combination thereof. In some embodiments, the therapeutic target is a4B7. In some embodiments, the therapeutic target is CCR6. In some embodiments, the therapeutic target is CD30 ligand. In some embodiments, the therapeutic target is FPR1. In some embodiments, the therapeutic target is GLP-2. In some embodiments, the therapeutic target is IL-2. In some embodiments, the therapeutic target is IL-4 / IL-13. In some embodiments, the therapeutic target is IL7R. In some embodiments, the therapeutic target is IL-10. In some embodiments, the therapeutic target is IL-12 / IL-23. In some embodiments, the therapeutic target is IL-36. In some embodiments, the therapeutic target is JAK. In some embodiments, the therapeutic target is JAK1. In some embodiments, the therapeutic target is JAK (ITK / TXK / JAK3). In some embodiments, the therapeutic target is JAK3 / TEC. In some embodiments, the therapeutic target is MC1r. In some embodiments, the therapeutic target is MRP2. In some embodiments, the therapeutic target is the NLRP3 inflammasome. In some embodiments, the therapeutic target is NLRX1. In some embodiments, the therapeutic target is PDE4. In some embodiments, the therapeutic target is PSGL-1. In some embodiments, the therapeutic target is RIPK1. In some embodiments, the therapeutic target is S1P1. In some embodiments, the therapeutic target is TL1A. In some embodiments, the therapeutic target is TLR9. In some embodiments, the therapeutic target is TNFα. In some embodiments, the therapeutic target is TNFSF15. In some embodiments, the therapeutic target is TPL2.In one embodiment, the therapeutic target is TREM1. In one embodiment, the therapeutic target is TYK2.
[0051] In some embodiments, the evaluation comprises monitoring mucosal lesions in the subject. In some embodiments, the evaluation comprises evaluating inflammation in the subject. In some embodiments, the evaluation of inflammation comprises analyzing the amount of inflammation. In some embodiments, the evaluation of inflammation comprises analyzing the increase or decrease of inflammation. In some embodiments, the evaluation of inflammation comprises analyzing changes in inflammation.
[0052] In some embodiments, the evaluation includes evaluating a cell type in the subject. In some embodiments, the evaluation includes analyzing the amount of a cell type. In some embodiments, the evaluation includes analyzing the increase or decrease of a cell type. In some embodiments, the evaluation includes analyzing changes in the relative proportion of a cell type. In some embodiments, the cell type is an inflammatory cell. In some embodiments, the cell type is an immunogenic cell. In some embodiments, the cell type is an enterocyte. In some embodiments, the cell type is an enterocyte-associated cell. In some embodiments, the cell type is a lymphocyte cell. In some embodiments, the cell type is a lymphocyte-associated cell. In some embodiments, the cell type is a T cell. In some embodiments, the cell type is an NK cell. In some embodiments, the cell type is a B cell. In some embodiments, the cell type is a macrophage. In some embodiments, the cell type is a neutrophil. In some embodiments, the cell type is an endothelial cell. In some embodiments, the cell type is a fibroblast.
[0053] In some embodiments, the therapeutic response is a response to a medical intervention in a subject. In some embodiments, the medical intervention is a medication. In some embodiments, the medication is an IBD medication. In some embodiments, the medication is a UC medication. In some embodiments, the medication is a CD medication. In some embodiments, the medication comprises an anti-inflammatory drug. In some embodiments, the medication comprises an immune system suppressant. In some embodiments, the medication comprises a biologic. In some embodiments, the medication comprises an antibiotic. The medical therapy can include, for example, adalimumab (Humira) or ustekinumab (Stelara) or vedolizumab (Entyvio) or infliximab (Remicade) or tofacitinib (Xeljanz) or certolizumab (Cimzia) or golimumab (Simponi) or natalizumab (Tysabri) or ozanimod (Zeposia) or risankizumab-rzaa (Skyrizi) or upadacitinib (Rinvoq) or etrasimod (Velspity) or mirikizumab or guselkumab or filgotinib. In certain embodiments, the medical intervention is a colonoscopy.
[0054] In some embodiments, measuring the expression level of a nucleic acid biomarker comprises extracting nucleic acid from a eukaryotic cell. In some embodiments, measuring the expression level of a nucleic acid biomarker comprises extracting DNA from a eukaryotic cell. In some embodiments, measuring the expression level of a nucleic acid biomarker comprises extracting RNA from a eukaryotic cell. In some embodiments, measuring the expression level of a nucleic acid biomarker comprises next-generation sequencing.
[0055] In some embodiments, the method further comprises the step of c) treating a disease in the subject. In some embodiments, the disease is inflammatory bowel disease (IBD). In some embodiments, the disease is ulcerative colitis (UC). In some embodiments, the disease is Crohn's disease (CD).
[0056] In some embodiments, treating the disease comprises administering to the subject an IBD medication. In some embodiments, treating the disease comprises administering to the subject a UC medication. In some embodiments, treating the disease comprises administering to the subject a CD medication. In some embodiments, treating the disease comprises administering to the subject an anti-inflammatory drug. In some embodiments, treating the disease comprises administering to the subject an immune system suppressant. In some embodiments, treating the disease comprises administering to the subject a biologic. In some embodiments, treating the disease comprises administering to the subject an antibiotic. Immune system suppressants can include, for example, adalimumab (Humira) or ustekinumab (Stelara) or vedolizumab (Entyvio) or infliximab (Remicade) or tofacitinib (Xeljanz) or certolizumab (Cimzia) or golimumab (Simponi) or natalizumab (Tysabri) or ozanimod (Zeposia) or risankizumab-rzaa (Skyrizi) or upadacitinib (Rinvoq) or etrasimod (Velspity) or mirikizumab or guselkumab or filgotinib.
[0057] In an exemplary embodiment, a method is provided for assessing the presence and / or mechanism of inflammation in a subject, the method comprising measuring the expression level of one or more stool-derived eukaryotic nucleic acid biomarkers selected from the biomarkers described herein in eukaryotic nucleic acid extracted from a stool sample from the subject, wherein the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample indicates an assessment of inflammation in the subject.
[0058] In certain embodiments, the method comprises comparing the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample with the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in a control, wherein a difference in the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample relative to the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the control indicates an assessment of inflammation in the subject.
[0059] In some embodiments, the nucleic acid is DNA. In some embodiments, the nucleic acid is RNA. In some embodiments, the nucleic acid is a combination of DNA and RNA.
[0060] In some embodiments, the inflammation is associated with a disease. In some embodiments, the disease is inflammatory bowel disease (IBD). In some embodiments, the disease is ulcerative colitis (UC). In some embodiments, the disease is Crohn's disease (CD).
[0061] In some embodiments, assessing inflammation includes assessing disease activity in the subject. In some embodiments, the assessment is determining active IBD symptoms in the subject. In some embodiments, determining active IBD symptoms indicates mild IBD symptoms. In some embodiments, determining active IBD symptoms indicates moderate IBD symptoms. In some embodiments, determining active IBD symptoms indicates severe IBD symptoms. In some embodiments, the assessment is determining IBD remission in the subject.
[0062] In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 1. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 2. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 3. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 4. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include a combination of biomarkers listed in Table 5.
[0063] In some embodiments, the one or more stool-derived eukaryotic nucleic acid biomarkers comprise stool-derived eukaryotic RNA biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise intestinal cell-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist essentially of intestinal cell-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist of intestinal cell-specific biomarkers.
[0064] In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise lymphocyte-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist essentially of lymphocyte-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist of lymphocyte-specific biomarkers.
[0065] In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise a gut cell-specific biomarker and a lymphocyte-specific biomarker. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist essentially of a gut cell-specific biomarker and a lymphocyte-specific biomarker. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist of a gut cell-specific biomarker and a lymphocyte-specific biomarker.
[0066] In some embodiments, the stool-derived eukaryotic RNA biomarkers include one or more non-therapeutic targets, hi some embodiments, the one or more non-therapeutic targets are selected from the group consisting of RNA transcripts that mediate cytoskeletal remodeling, proliferation, and inflammatory responses.
[0067] In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise one or more therapeutic targets. In some embodiments, the one or more therapeutic targets are selected from the group consisting of a4B7, CCR6, CD30 ligand, FPR1, GLP-2, IL-2, IL-4 / IL-13, IL7R, IL-10, IL-12 / IL-23, IL-36, JAK, JAK1, JAK(ITK / TXK / JAK3), JAK3 / TEC, MC1r, MRP2, NLRP3 inflammasome, NLRX1, PDE4, PSGL-1, RIPK1, S1P1, TL1A, TLR9, TNFα, TNFSF15, TPL2, TREM1, TYK2, and any combination thereof. In some embodiments, the therapeutic target is a4B7. In some embodiments, the therapeutic target is CCR6. In some embodiments, the therapeutic target is CD30 ligand. In some embodiments, the therapeutic target is FPR1. In some embodiments, the therapeutic target is GLP-2. In some embodiments, the therapeutic target is IL-2. In some embodiments, the therapeutic target is IL-4 / IL-13. In some embodiments, the therapeutic target is IL7R. In some embodiments, the therapeutic target is IL-10. In some embodiments, the therapeutic target is IL-12 / IL-23. In some embodiments, the therapeutic target is IL-36. In some embodiments, the therapeutic target is JAK. In some embodiments, the therapeutic target is JAK1. In some embodiments, the therapeutic target is JAK (ITK / TXK / JAK3). In some embodiments, the therapeutic target is JAK3 / TEC. In some embodiments, the therapeutic target is MC1r. In some embodiments, the therapeutic target is MRP2. In some embodiments, the therapeutic target is the NLRP3 inflammasome. In some embodiments, the therapeutic target is NLRX1. In some embodiments, the therapeutic target is PDE4. In some embodiments, the therapeutic target is PSGL-1. In some embodiments, the therapeutic target is RIPK1. In some embodiments, the therapeutic target is S1P1. In some embodiments, the therapeutic target is TL1A. In some embodiments, the therapeutic target is TLR9. In some embodiments, the therapeutic target is TNFα. In some embodiments, the therapeutic target is TNFSF15. In some embodiments, the therapeutic target is TPL2.In one embodiment, the therapeutic target is TREM1. In one embodiment, the therapeutic target is TYK2.
[0068] In some embodiments, the evaluation comprises monitoring mucosal lesions in the subject. In some embodiments, the evaluation comprises evaluating inflammation in the subject. In some embodiments, the evaluation of inflammation comprises analyzing the amount of inflammation. In some embodiments, the evaluation of inflammation comprises analyzing the increase or decrease of inflammation. In some embodiments, the evaluation of inflammation comprises analyzing changes in inflammation.
[0069] In some embodiments, the evaluation includes evaluating a cell type in the subject. In some embodiments, the evaluation includes analyzing the amount of a cell type. In some embodiments, the evaluation includes analyzing the increase or decrease of a cell type. In some embodiments, the evaluation includes analyzing changes in the relative proportion of a cell type. In some embodiments, the cell type is an inflammatory cell. In some embodiments, the cell type is an immunogenic cell. In some embodiments, the cell type is an enterocyte. In some embodiments, the cell type is an enterocyte-associated cell. In some embodiments, the cell type is a lymphocyte cell. In some embodiments, the cell type is a lymphocyte-associated cell. In some embodiments, the cell type is a T cell. In some embodiments, the cell type is an NK cell. In some embodiments, the cell type is a B cell. In some embodiments, the cell type is a macrophage. In some embodiments, the cell type is a neutrophil. In some embodiments, the cell type is an endothelial cell. In some embodiments, the cell type is a fibroblast.
[0070] In some embodiments, the evaluation comprises a prognosis of a therapeutic response to a medical intervention in a subject. In some embodiments, the medical intervention is a medication. In some embodiments, the medication is an IBD medication. In some embodiments, the medication is a UC medication. In some embodiments, the medication is a CD medication. In some embodiments, the medication comprises an anti-inflammatory drug. In some embodiments, the medication comprises an immune system suppressant. In some embodiments, the medication comprises a biologic. In some embodiments, the medication comprises an antibiotic. The medical therapy can include, for example, adalimumab (Humira) or ustekinumab (Stelara) or vedolizumab (Entyvio) or infliximab (Remicade) or tofacitinib (Xeljanz) or certolizumab (Cimzia) or golimumab (Simponi) or natalizumab (Tysabri) or ozanimod (Zeposia) or risankizumab-rzaa (Skyrizi) or upadacitinib (Rinvoq) or etrasimod (Velspity) or mirikizumab or guselkumab or filgotinib. In certain embodiments, the medical intervention is a colonoscopy.
[0071] In some embodiments, the evaluation comprises determining the therapeutic effectiveness of a medical intervention in the subject. In some embodiments, the medical intervention is a medication. In some embodiments, the medication is an IBD medication. In some embodiments, the medication is a UC medication. In some embodiments, the medication is a CD medication. In some embodiments, the medication comprises an anti-inflammatory drug. In some embodiments, the medication comprises an immune system suppressant. In some embodiments, the medication comprises a biologic. In some embodiments, the medication comprises an antibiotic. The medical therapy can include, for example, adalimumab (Humira) or ustekinumab (Stelara) or vedolizumab (Entyvio) or infliximab (Remicade) or tofacitinib (Xeljanz) or certolizumab (Cimzia) or golimumab (Simponi) or natalizumab (Tysabri) or ozanimod (Zeposia) or risankizumab-rzaa (Skyrizi) or upadacitinib (Rinvoq) or etrasimod (Velspity) or mirikizumab or guselkumab or filgotinib. In certain embodiments, the medical intervention is a colonoscopy.
[0072] In some embodiments, measuring the expression level of a nucleic acid biomarker comprises extracting nucleic acid from a eukaryotic cell. In some embodiments, measuring the expression level of a nucleic acid biomarker comprises extracting DNA from a eukaryotic cell. In some embodiments, measuring the expression level of a nucleic acid biomarker comprises extracting RNA from a eukaryotic cell. In some embodiments, measuring the expression level of a nucleic acid biomarker comprises next-generation sequencing.
[0073] In some embodiments, the method further comprises the step of c) diagnosing the disease in the subject. In some embodiments, the disease is inflammatory bowel disease (IBD). In some embodiments, the disease is ulcerative colitis (UC). In some embodiments, the disease is Crohn's disease (CD).
[0074] In some embodiments, the method further comprises c) treating the disease in the subject. In some embodiments, the disease is inflammatory bowel disease (IBD). In some embodiments, the disease is ulcerative colitis (UC). In some embodiments, the disease is Crohn's disease (CD). In some embodiments, treating the disease comprises administering an IBD medication to the subject. In some embodiments, treating the disease comprises administering a UC medication to the subject. In some embodiments, treating the disease comprises administering a CD medication to the subject. In some embodiments, treating the disease comprises administering an anti-inflammatory drug to the subject. In some embodiments, treating the disease comprises administering an immune system suppressant to the subject. In some embodiments, treating the disease comprises administering a biologic to the subject. In some embodiments, treating the disease comprises administering an antibiotic to the subject. Immune system suppressants can include, for example, adalimumab (Humira) or ustekinumab (Stelara) or vedolizumab (Entyvio) or infliximab (Remicade) or tofacitinib (Xeljanz) or certolizumab (Cimzia) or golimumab (Simponi) or natalizumab (Tysabri) or ozanimod (Zeposia) or risankizumab-rzaa (Skyrizi) or upadacitinib (Rinvoq) or etrasimod (Velspity) or mirikizumab or guselkumab or filgotinib.
[0075] In an exemplary embodiment, a method for assessing one or more immune cells or immune-related cells in a subject is provided. The method includes measuring the expression level of one or more stool-derived eukaryotic nucleic acid biomarkers selected from the biomarkers described herein in eukaryotic nucleic acid extracted from a stool sample from the subject, wherein the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample indicates the assessment of one or more immune cells in the subject. By way of example, the immune-related cells may include fibroblasts, stromal cells, etc.
[0076] In certain embodiments, the method comprises comparing the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample with the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in a control, wherein a difference in the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample relative to the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the control indicates an assessment of immune cells in the subject.
[0077] In some embodiments, the nucleic acid is DNA. In some embodiments, the nucleic acid is RNA. In some embodiments, the nucleic acid is a combination of DNA and RNA.
[0078] In some embodiments, the immune cells are associated with a disease. In some embodiments, the disease is inflammatory bowel disease (IBD). In some embodiments, the disease is ulcerative colitis (UC). In some embodiments, the disease is Crohn's disease (CD).
[0079] In some embodiments, the evaluation of immune cells comprises evaluating disease activity in the subject. In some embodiments, the evaluation is determining active IBD symptoms in the subject. In some embodiments, the determination of active IBD symptoms indicates mild IBD symptoms. In some embodiments, the determination of active IBD symptoms indicates moderate IBD symptoms. In some embodiments, the determination of active IBD symptoms indicates severe IBD symptoms. In some embodiments, the evaluation is determining IBD remission in the subject.
[0080] In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 1. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 2. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 3. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 4. In some embodiments, the stool-derived eukaryotic nucleic acid biomarkers include a combination of biomarkers listed in Table 5.
[0081] In some embodiments, the one or more stool-derived eukaryotic nucleic acid biomarkers comprise stool-derived eukaryotic RNA biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise intestinal cell-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist essentially of intestinal cell-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist of intestinal cell-specific biomarkers.
[0082] In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise lymphocyte-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist essentially of lymphocyte-specific biomarkers. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist of lymphocyte-specific biomarkers.
[0083] In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise a gut cell-specific biomarker and a lymphocyte-specific biomarker. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist essentially of a gut cell-specific biomarker and a lymphocyte-specific biomarker. In some embodiments, the stool-derived eukaryotic RNA biomarkers consist of a gut cell-specific biomarker and a lymphocyte-specific biomarker.
[0084] In some embodiments, the stool-derived eukaryotic RNA biomarkers include one or more non-therapeutic targets, hi some embodiments, the one or more non-therapeutic targets are selected from the group consisting of RNA transcripts that mediate cytoskeletal remodeling, proliferation, and inflammatory responses.
[0085] In some embodiments, the stool-derived eukaryotic RNA biomarkers comprise one or more therapeutic targets. In some embodiments, the one or more therapeutic targets are selected from the group consisting of a4B7, CCR6, CD30 ligand, FPR1, GLP-2, IL-2, IL-4 / IL-13, IL7R, IL-10, IL-12 / IL-23, IL-36, JAK, JAK1, JAK(ITK / TXK / JAK3), JAK3 / TEC, MC1r, MRP2, NLRP3 inflammasome, NLRX1, PDE4, PSGL-1, RIPK1, S1P1, TL1A, TLR9, TNFα, TNFSF15, TPL2, TREM1, TYK2, and any combination thereof. In some embodiments, the therapeutic target is a4B7. In some embodiments, the therapeutic target is CCR6. In some embodiments, the therapeutic target is CD30 ligand. In some embodiments, the therapeutic target is FPR1. In some embodiments, the therapeutic target is GLP-2. In some embodiments, the therapeutic target is IL-2. In some embodiments, the therapeutic target is IL-4 / IL-13. In some embodiments, the therapeutic target is IL7R. In some embodiments, the therapeutic target is IL-10. In some embodiments, the therapeutic target is IL-12 / IL-23. In some embodiments, the therapeutic target is IL-36. In some embodiments, the therapeutic target is JAK. In some embodiments, the therapeutic target is JAK1. In some embodiments, the therapeutic target is JAK (ITK / TXK / JAK3). In some embodiments, the therapeutic target is JAK3 / TEC. In some embodiments, the therapeutic target is MC1r. In some embodiments, the therapeutic target is MRP2. In some embodiments, the therapeutic target is the NLRP3 inflammasome. In some embodiments, the therapeutic target is NLRX1. In some embodiments, the therapeutic target is PDE4. In some embodiments, the therapeutic target is PSGL-1. In some embodiments, the therapeutic target is RIPK1. In some embodiments, the therapeutic target is S1P1. In some embodiments, the therapeutic target is TL1A. In some embodiments, the therapeutic target is TLR9. In some embodiments, the therapeutic target is TNFα. In some embodiments, the therapeutic target is TNFSF15. In some embodiments, the therapeutic target is TPL2.In one embodiment, the therapeutic target is TREM1. In one embodiment, the therapeutic target is TYK2.
[0086] In some embodiments, the evaluation comprises monitoring mucosal lesions in the subject. In some embodiments, the evaluation comprises evaluating inflammation in the subject. In some embodiments, the evaluation of inflammation comprises analyzing the amount of inflammation. In some embodiments, the evaluation of inflammation comprises analyzing the increase or decrease of inflammation. In some embodiments, the evaluation of inflammation comprises analyzing changes in inflammation.
[0087] In some embodiments, the evaluation includes evaluating a cell type in the subject. In some embodiments, the evaluation includes analyzing the amount of a cell type. In some embodiments, the evaluation includes analyzing the increase or decrease of a cell type. In some embodiments, the evaluation includes analyzing changes in the relative proportion of a cell type. In some embodiments, the cell type is an inflammatory cell. In some embodiments, the cell type is an immunogenic cell. In some embodiments, the cell type is an enterocyte. In some embodiments, the cell type is an enterocyte-associated cell. In some embodiments, the cell type is a lymphocyte cell. In some embodiments, the cell type is a lymphocyte-associated cell. In some embodiments, the cell type is a T cell. In some embodiments, the cell type is an NK cell. In some embodiments, the cell type is a B cell. In some embodiments, the cell type is a macrophage. In some embodiments, the cell type is a neutrophil. In some embodiments, the cell type is an endothelial cell. In some embodiments, the cell type is a fibroblast.
[0088] In some embodiments, the assessment is a prognosis of a therapeutic response to a medical intervention in a subject. In some embodiments, the medical intervention is a medication. In some embodiments, the medication is an IBD medication. In some embodiments, the medication is a UC medication. In some embodiments, the medication is a CD medication. In some embodiments, the medication comprises an anti-inflammatory drug. In some embodiments, the medication comprises an immune system suppressant. In some embodiments, the medication comprises a biologic. In some embodiments, the medication comprises an antibiotic. In some embodiments, the medical intervention is a colonoscopy. The medication may include, for example, adalimumab (Humira) or ustekinumab (Stelara) or vedolizumab (Entyvio) or infliximab (Remicade) or tofacitinib (Xeljanz) or certolizumab (Cimzia) or golimumab (Simponi) or natalizumab (Tysabri) or ozanimod (Zeposia) or risankizumab-rzaa (Skyrizi) or upadacitinib (Rinvoq) or etrasimod (Velspity) or mirikizumab or guselkumab or filgotinib.
[0089] In some embodiments, the evaluation is a determination of the therapeutic effectiveness of a medical intervention in a subject. In some embodiments, the medical intervention is a medication. In some embodiments, the medication is an IBD medication. In some embodiments, the medication is a UC medication. In some embodiments, the medication is a CD medication. In some embodiments, the medication comprises an anti-inflammatory drug. In some embodiments, the medication comprises an immune system suppressant. In some embodiments, the medication comprises a biologic. In some embodiments, the medication comprises an antibiotic. In some embodiments, the medical intervention is a colonoscopy. The medication may include, for example, adalimumab (Humira) or ustekinumab (Stelara) or vedolizumab (Entyvio) or infliximab (Remicade) or tofacitinib (Xeljanz) or certolizumab (Cimzia) or golimumab (Simponi) or natalizumab (Tysabri) or ozanimod (Zeposia) or risankizumab-rzaa (Skyrizi) or upadacitinib (Rinvoq) or etrasimod (Velspity) or mirikizumab or guselkumab or filgotinib.
[0090] In some embodiments, measuring the expression level of a nucleic acid biomarker comprises extracting nucleic acid from a eukaryotic cell. In some embodiments, measuring the expression level of a nucleic acid biomarker comprises extracting DNA from a eukaryotic cell. In some embodiments, measuring the expression level of a nucleic acid biomarker comprises extracting RNA from a eukaryotic cell. In some embodiments, measuring the expression level of a nucleic acid biomarker comprises next-generation sequencing.
[0091] In some embodiments, the method further comprises the step of c) diagnosing the disease in the subject. In some embodiments, the disease is inflammatory bowel disease (IBD). In some embodiments, the disease is ulcerative colitis (UC). In some embodiments, the disease is Crohn's disease (CD).
[0092] In some embodiments, the method further comprises c) treating the disease in the subject. In some embodiments, the disease is inflammatory bowel disease (IBD). In some embodiments, the disease is ulcerative colitis (UC). In some embodiments, the disease is Crohn's disease (CD). In some embodiments, treating the disease comprises administering an IBD medication to the subject. In some embodiments, treating the disease comprises administering a UC medication to the subject. In some embodiments, treating the disease comprises administering a CD medication to the subject. In some embodiments, treating the disease comprises administering an anti-inflammatory drug to the subject. In some embodiments, treating the disease comprises administering an immune system suppressant to the subject. In some embodiments, treating the disease comprises administering a biologic to the subject. In some embodiments, treating the disease comprises administering an antibiotic to the subject. Immune system suppressants can include, for example, adalimumab (Humira) or ustekinumab (Stelara) or vedolizumab (Entyvio) or infliximab (Remicade) or tofacitinib (Xeljanz) or certolizumab (Cimzia) or golimumab (Simponi) or natalizumab (Tysabri) or ozanimod (Zeposia) or risankizumab-rzaa (Skyrizi) or upadacitinib (Rinvoq) or etrasimod (Velspity) or mirikizumab or guselkumab or filgotinib.
[0093] Consider the following numbered embodiments, which are non-limiting: 1. A method for assessing a disease in a subject, comprising: measuring the expression level of one or more stool-derived eukaryotic nucleic acid biomarkers selected from the biomarkers described herein in eukaryotic nucleic acid extracted from a stool sample from the subject; Including, A method wherein the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in a stool sample is indicative of an assessment of disease in the subject. 2. The method of clause 1, any other suitable clause, or any combination of suitable clauses, comprising comparing the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in a stool sample with the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in a control, wherein a difference in the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample relative to the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the control indicates an assessment of disease in the subject. 3. The method of paragraph 1, any other suitable paragraph, or any combination of suitable paragraphs, wherein the nucleic acid is DNA. 4. The method of paragraph 1, any other suitable paragraph, or any combination of suitable paragraphs, wherein the nucleic acid is RNA. 5. The method of paragraph 1, any other suitable paragraph, or any combination of suitable paragraphs, wherein the nucleic acid is a combination of DNA and RNA. 6. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the disease is inflammatory bowel disease (IBD). 7. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the disease is ulcerative colitis (UC). 8. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the disease is Crohn's disease (CD). 9. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein assessing the disease comprises assessing disease activity in the subject. 10. The method of clause 9, any other suitable clause, or any combination of suitable clauses, wherein the assessment is a determination of active IBD symptoms in the subject. 11. The method of clause 10, any other suitable clause, or any combination of suitable clauses, wherein the determination of active IBD symptoms indicates mild IBD symptoms. 12. The method of clause 10, any other suitable clause, or any combination of suitable clauses, wherein the determination of active IBD symptoms indicates moderate IBD symptoms. 13. The method of clause 10, any other suitable clause, or any combination of suitable clauses, wherein the determination of active IBD symptoms indicates severe IBD symptoms. 14. The method of clause 9, any other suitable clause, or any combination of suitable clauses, wherein the assessment is a determination of IBD remission in the subject. 15. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 1. 16. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 2. 17. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 3. 18. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 4. 19. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise a combination of biomarkers listed in Table 5. 20. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the one or more stool-derived eukaryotic nucleic acid biomarkers comprise a stool-derived eukaryotic RNA biomarker. 21. The method of clause 20, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic RNA biomarkers comprise enterocyte-specific biomarkers. 22. The method of clause 20, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic RNA biomarkers consist essentially of enterocyte-specific biomarkers. 23. The method of clause 20, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic RNA biomarkers consist of enterocyte-specific biomarkers. 24. The method of clause 20, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic RNA biomarkers comprise lymphocyte-specific biomarkers. 25. The method of clause 20, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic RNA biomarkers consist essentially of lymphocyte-specific biomarkers. 26. The method of clause 20, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic RNA biomarkers consist of lymphocyte-specific biomarkers. 27. The method of clause 20, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic RNA biomarkers include enterocyte-specific biomarkers and lymphocyte-specific biomarkers. 28. The method of clause 20, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic RNA biomarkers consist essentially of enterocyte-specific biomarkers and lymphocyte-specific biomarkers. 29. The method of clause 20, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic RNA biomarkers consist of enterocyte-specific biomarkers and lymphocyte-specific biomarkers. 30. The method of clause 20, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic RNA biomarkers include one or more non-therapeutic targets. 31. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the one or more non-therapeutic targets are selected from the group consisting of RNA transcripts that mediate cytoskeletal remodeling, proliferation, and inflammatory responses. 32. The method of clause 20, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic RNA biomarkers comprise one or more therapeutic targets. 33. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the one or more therapeutic targets are selected from the group consisting of TNF, MADCAM1, ITGA4, JAK1, TYK2, IL-12, IL-23, and any combination thereof. 34. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TNF. 35. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is MADCAM1. 36. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is ITGA4. 37. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is JAK1. 38. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TYK2. 39. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is IL-12. 40. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is IL-23. 41. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the one or more therapeutic targets are selected from the group consisting of a4B7, CCR6, CD30 ligand, FPR1, GLP-2, IL-2, IL-4 / IL-13, IL7R, IL-10, IL-12 / IL-23, IL-36, JAK, JAK1, JAK(ITK / TXK / JAK3), JAK3 / TEC, MC1r, MRP2, NLRP3 inflammasome, NLRX1, PDE4, PSGL-1, RIPK1, S1P1, TL1A, TLR9, TNFα, TNFSF15, TPL2, TREM1, TYK2, and any combination thereof. 42. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is a4B7. 43. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is CCR6. 44. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is CD30 ligand. 45. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is FPR1. 46. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is GLP-2. 47. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is IL-2. 48. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is IL-4 / IL-13. 49. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is IL7R. 50. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is IL-10. 51. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is IL-12 / IL-23. 52. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is IL-36. 53. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is JAK. 54. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is JAK1. 55. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is JAK (ITK / TXK / JAK3). 56. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is JAK3 / TEC. 57. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is MC1r. 58. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is MRP2. 59. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is the NLRP3 inflammasome. 60. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is NLRX1. 61. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is PDE4. 62. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is PSGL-1. 63. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is RIPK1. 64. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is S1P1. 65. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TL1A. 66. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TLR9. 67. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TNFα. 68. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TNFSF15. 69. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TPL2. 70. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TREM1. 71. The method of clause 32, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TYK2. 72. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the assessment comprises monitoring mucosal lesions in the subject. 73. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the assessment includes assessment of inflammation in the subject. 74. The method of clause 73, any other suitable clause, or any combination of suitable clauses, wherein assessing inflammation comprises analyzing the amount of inflammation. 75. The method of clause 73, any other suitable clause, or any combination of suitable clauses, wherein assessing inflammation comprises analyzing increases or decreases in inflammation. 76. The method of clause 73, any other suitable clause, or any combination of suitable clauses, wherein assessing inflammation comprises analyzing changes in inflammation. 77. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein assessing comprises assessing a cell type in the subject. 78. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the assessment comprises analysis of the abundance of cell types. 79. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the evaluation comprises analysis of cell type gain or loss. 80. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the evaluation comprises analysis of changes in the relative proportions of cell types. 81. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the cell type is an inflammatory cell. 82. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the cell type is an immunogenic cell. 83. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the cell type is an intestinal cell. 84. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the cell type is an enterocyte-associated cell. 85. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the cell type is a lymphocyte cell. 86. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the cell type is a lymphocyte-related cell. 87. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the cell type is a T cell. 88. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the cell type is a NK cell. 89. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the cell type is a B cell. 90. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the cell type is a macrophage. 91. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the cell type is a neutrophil. 92. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the cell type is an endothelial cell. 93. The method of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the cell type is a fibroblast. 94. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the assessment is prognostic of a therapeutic response to a medical intervention in the subject. 95. The method of clause 94, any other suitable clause, or any combination of suitable clauses, wherein the medical intervention is a drug therapy. 96. The method of clause 95, any other suitable clause, or any combination of suitable clauses, wherein the medication is an IBD medication. 97. The method of clause 95, any other suitable clause, or any combination of suitable clauses, wherein the medication is a UC medication. 98. The method of clause 95, any other suitable clause, or any combination of suitable clauses, wherein the medication is a CD medication. 99. The method of clause 95, any other suitable clause, or any combination of suitable clauses, wherein the medication comprises an anti-inflammatory drug. 100. The method of clause 95, any other suitable clause, or any combination of suitable clauses, wherein the medication comprises an immune system suppressant. 101. The method of clause 95, any other suitable clause, or any combination of suitable clauses, wherein the medical therapy includes a biologic. 102. The method of clause 95, any other suitable clause, or any combination of suitable clauses, wherein the medical therapy includes an antibiotic. 103. The method of clause 94, any other suitable clause, or any combination of suitable clauses, wherein the medical intervention is a colonoscopy. 104. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the assessment is a determination of the therapeutic efficacy of a medical intervention in the subject. 105. The method of clause 104, any other suitable clause, or any combination of suitable clauses, wherein the medical intervention is a drug therapy. 106. The method of clause 105, any other suitable clause, or any combination of suitable clauses, wherein the medication is an IBD medication. 107. The method of clause 105, any other suitable clause, or any combination of suitable clauses, wherein the medication is a UC medication. 108. The method of clause 105, any other suitable clause, or any combination of suitable clauses, wherein the medication is a CD medication. 109. The method of clause 105, any other suitable clause, or any combination of suitable clauses, wherein the medication comprises an anti-inflammatory drug. 110. The method of clause 105, any other suitable clause, or any combination of suitable clauses, wherein the medication comprises an immune system suppressant. 111. The method of clause 105, any other suitable clause, or any combination of suitable clauses, wherein the medical therapy includes a biologic. 112. The method of clause 105, any other suitable clause, or any combination of suitable clauses, wherein the medical therapy includes an antibiotic. 113. The method of clause 104, any other suitable clause, or any combination of suitable clauses, wherein the medical intervention is a colonoscopy. 114. The method of paragraph 1, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring the expression level of the nucleic acid biomarker comprises extracting nucleic acid from a eukaryotic cell. 115. The method of paragraph 1, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring the expression level of the nucleic acid biomarker comprises extracting DNA from eukaryotic cells. 116. The method of paragraph 1, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring the expression level of the nucleic acid biomarker comprises RNA extraction from eukaryotic cells. 117. The method of clause 1, any other suitable clause, or any combination of suitable clauses, wherein measuring the expression levels of nucleic acid biomarkers comprises next generation sequencing. 118. The method of clause 1, any other suitable clause, or any combination of suitable clauses, further comprising diagnosing the disease in the subject. 119. The method of clause 118, any other suitable clause, or any combination of suitable clauses, wherein the disease is inflammatory bowel disease (IBD). 120. The method of clause 118, any other suitable clause, or any combination of suitable clauses, wherein the disease is ulcerative colitis (UC). 121. The method of clause 118, any other suitable clause, or any combination of suitable clauses, wherein the disease is Crohn's disease (CD). 122. The method of clause 1, any other suitable clause, or any combination of suitable clauses, further comprising treating a disease in a subject. 123. The method of clause 122, any other suitable clause, or any combination of suitable clauses, wherein the disease is inflammatory bowel disease (IBD). 124. The method of clause 122, any other suitable clause, or any combination of suitable clauses, wherein the disease is ulcerative colitis (UC). 125. The method of clause 122, any other suitable clause, or any combination of suitable clauses, wherein the disease is Crohn's disease (CD). 126. The method of clause 122, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject an IBD medication. 127. The method of clause 122, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject a UC medication. 128. The method of clause 122, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject a CD medication. 129. The method of clause 122, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering an anti-inflammatory agent to the subject. 130. The method of clause 122, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject an immune system suppressant. 131. The method of clause 122, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject a biologic. 132. The method of clause 122, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering an antibiotic to the subject. 133. A method for predicting a therapeutic response to a disease in a subject, comprising: measuring the expression level of one or more stool-derived eukaryotic nucleic acid biomarkers selected from the biomarkers described herein in eukaryotic nucleic acid extracted from a stool sample from the subject; Including, A method wherein the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in a stool sample is indicative of a treatment response to a disease in the subject. 134. The method of paragraph 133, any other suitable paragraph, or any combination of suitable paragraphs, comprising comparing the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in a stool sample with the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in a control, wherein a difference in the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample relative to the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the control indicates a treatment response to a disease in the subject. 135. The method of paragraph 133, any other suitable paragraph, or any combination of suitable paragraphs, wherein the nucleic acid is DNA. 136. The method of clause 133, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid is RNA. 137. The method of paragraph 133, any other suitable paragraph, or any combination of suitable paragraphs, wherein the nucleic acid is a combination of DNA and RNA. 138. The method of clause 133, any other suitable clause, or any combination of suitable clauses, wherein the disease is inflammatory bowel disease (IBD). 139. The method of clause 133, any other suitable clause, or any combination of suitable clauses, wherein the disease is ulcerative colitis (UC). 140. The method of clause 133, any other suitable clause, or any combination of suitable clauses, wherein the disease is Crohn's disease (CD). 141. The method of clause 133, any other suitable clause, or any combination of suitable clauses, wherein the treatment response comprises an assessment of disease activity in the subject. 142. The method of clause 141, any other suitable clause, or any combination of suitable clauses, wherein the assessment is a determination of active IBD symptoms in the subject. 143. The method of clause 142, any other suitable clause, or any combination of suitable clauses, wherein the determination of active IBD symptoms indicates mild IBD symptoms. 144. The method of clause 142, any other suitable clause, or any combination of suitable clauses, wherein the determination of active IBD symptoms indicates moderate IBD symptoms. 145. The method of clause 142, any other suitable clause, or any combination of suitable clauses, wherein the determination of active IBD symptoms indicates severe IBD symptoms. 146. The method of clause 133, any other suitable clause, or any combination of suitable clauses, wherein the assessment is a determination of IBD remission in the subject. 147. The method of clause 133, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 1. 148. The method of clause 133, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 2. 149. The method of clause 133, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 3. 150. The method of clause 133, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 4. 151. The method of paragraph 133, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise a combination of biomarkers listed in Table 5. 152. The method of paragraph 133, any other suitable paragraph, or any combination of suitable paragraphs, wherein the one or more stool-derived eukaryotic nucleic acid biomarkers comprise stool-derived eukaryotic RNA biomarkers. 153. The method of paragraph 152, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers include enterocyte-specific biomarkers. 154. The method of paragraph 152, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist essentially of enterocyte-specific biomarkers. 155. The method of paragraph 152, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist of enterocyte-specific biomarkers. 156. The method of paragraph 152, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers include lymphocyte-specific biomarkers. 157. The method of paragraph 152, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist essentially of lymphocyte-specific biomarkers. 158. The method of paragraph 152, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist of lymphocyte-specific biomarkers. 159. The method of paragraph 152, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers include enterocyte-specific biomarkers and lymphocyte-specific biomarkers. 160. The method of paragraph 152, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist essentially of enterocyte-specific biomarkers and lymphocyte-specific biomarkers. 161. The method of paragraph 152, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist of enterocyte-specific biomarkers and lymphocyte-specific biomarkers. 162. The method of paragraph 152, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers include one or more non-therapeutic targets. 163. The method of paragraph 162, any other suitable paragraph, or any combination of suitable paragraphs, wherein the one or more non-therapeutic targets are selected from the group consisting of RNA transcripts that mediate cytoskeletal remodeling, proliferation, and inflammatory responses. 164. The method of paragraph 152, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers comprise one or more therapeutic targets. 165. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the one or more therapeutic targets are selected from the group consisting of TNF, MADCAM1, ITGA4, JAK1, TYK2, IL-12, IL-23, and any combination thereof. 166. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TNF. 167. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is MADCAM1. 168. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is ITGA4. 169. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is JAK1. 170. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TYK2. 171. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is IL-12. 172. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-23. 173. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the one or more therapeutic targets are selected from the group consisting of a4B7, CCR6, CD30 ligand, FPR1, GLP-2, IL-2, IL-4 / IL-13, IL7R, IL-10, IL-12 / IL-23, IL-36, JAK, JAK1, JAK(ITK / TXK / JAK3), JAK3 / TEC, MC1r, MRP2, NLRP3 inflammasome, NLRX1, PDE4, PSGL-1, RIPK1, S1P1, TL1A, TLR9, TNFα, TNFSF15, TPL2, TREM1, TYK2, and any combination thereof. 174. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is a4B7. 175. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is CCR6. 176. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is CD30 ligand. 177. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is FPR1. 178. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is GLP-2. 179. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is IL-2. 180. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-4 / IL-13. 181. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is IL7R. 182. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-10. 183. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-12 / IL-23. 184. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is IL-36. 185. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is JAK. 186. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is JAK1. 187. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is JAK (ITK / TXK / JAK3). 188. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is JAK3 / TEC. 189. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is MC1r. 190. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is MRP2. 191. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is the NLRP3 inflammasome. 192. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is NLRX1. 193. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is PDE4. 194. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is PSGL-1. 195. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is RIPK1. 196. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is S1P1. 197. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TL1A. 198. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TLR9. 199. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TNFα. 200. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TNFSF15. 201. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TPL2. 202. The method of clause 164, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is TREM1. 203. The method of paragraph 164, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TYK2. 204. The method of paragraph 133, any other suitable paragraph, or any combination of suitable paragraphs, wherein assessing includes assessing inflammation in the subject. 205. The method of paragraph 204, any other suitable paragraph, or any combination of suitable paragraphs, wherein assessing inflammation includes analyzing the amount of inflammation. 206. The method of paragraph 204, any other suitable paragraph, or any combination of suitable paragraphs, wherein assessing inflammation includes analyzing increases or decreases in inflammation. 207. The method of paragraph 204, any other suitable paragraph, or any combination of suitable paragraphs, wherein assessing inflammation includes analyzing changes in inflammation. 208. The method of paragraph 133, any other suitable paragraph, or any combination of suitable paragraphs, wherein assessing comprises assessing a cell type in the subject. 209. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the evaluation includes analysis of the abundance of cell types. 210. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the evaluation includes analysis of cell type gain or loss. 211. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the evaluation comprises analysis of changes in the relative proportions of cell types. 212. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is an inflammatory cell. 213. The method of clause 208, any other suitable clause, or any combination of suitable clauses, wherein the cell type is an immunogenic cell. 214. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is an intestinal cell. 215. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is an enterocyte-associated cell. 216. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a lymphocyte cell. 217. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a lymphocyte-related cell. 218. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a T cell. 219. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a NK cell. 220. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a B cell. 221. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a macrophage. 222. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a neutrophil. 223. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is an endothelial cell. 224. The method of paragraph 208, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a fibroblast. 225. The method of clause 133, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic response is a response to a medical intervention in the subject. 226. The method of paragraph 225, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical intervention is a drug therapy. 227. The method of clause 226, any other suitable clause, or any combination of suitable clauses, wherein the medication is an IBD medication. 228. The method of paragraph 226, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication is a UC medication. 229. The method of clause 226, any other suitable clause, or any combination of suitable clauses, wherein the medication is a CD medication. 230. The method of paragraph 226, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication comprises an anti-inflammatory drug. 231. The method of clause 226, any other suitable clause, or any combination of suitable clauses, wherein the medication comprises an immune system suppressant. 232. The method of paragraph 226, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical therapy includes a biologic. 233. The method of paragraph 226, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical therapy includes an antibiotic. 234. The method of clause 225, any other suitable clause, or any combination of suitable clauses, wherein the medical intervention is a colonoscopy. 235. The method of paragraph 133, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring the expression level of the nucleic acid biomarker comprises extracting nucleic acid from a eukaryotic cell. 236. The method of paragraph 133, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring the expression level of the nucleic acid biomarker comprises extracting DNA from eukaryotic cells. 237. The method of paragraph 133, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring the expression level of the nucleic acid biomarker comprises RNA extraction from eukaryotic cells. 238. The method of paragraph 133, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring the expression levels of nucleic acid biomarkers comprises next generation sequencing. 239.c) The method of clause 133, any other suitable clause, or any combination of suitable clauses, further comprising treating a disease in the subject. 240. The method of clause 239, any other suitable clause, or any combination of suitable clauses, wherein the disease is inflammatory bowel disease (IBD). 241. The method of clause 239, any other suitable clause, or any combination of suitable clauses, wherein the disease is ulcerative colitis (UC). 242. The method of clause 239, any other suitable clause, or any combination of suitable clauses, wherein the disease is Crohn's disease (CD). 243. The method of clause 239, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject an IBD medication. 244. The method of clause 239, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject a UC medication. 245. The method of clause 239, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject a CD medication. 246. The method of clause 239, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject an anti-inflammatory drug. 247. The method of clause 239, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject an immune system suppressant. 248. The method of clause 239, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject a biologic. 249. The method of clause 239, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering an antibiotic to the subject. 250. A method for assessing inflammation in a subject, comprising: measuring the expression level of one or more stool-derived eukaryotic nucleic acid biomarkers selected from the biomarkers described herein in eukaryotic nucleic acid extracted from a stool sample from the subject; Including, The method, wherein the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample indicates an assessment of inflammation in the subject. 251. The method of clause 250, any other suitable clause, or any combination of suitable clauses, comprising comparing the measured expression level of one or more fecal-derived eukaryotic nucleic acid biomarkers in a stool sample with the measured expression level of one or more fecal-derived eukaryotic nucleic acid biomarkers in a control, wherein a difference in the measured expression level of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the stool sample relative to the measured expression level of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the control indicates an assessment of inflammation in the subject. 252. The method of paragraph 250, any other suitable paragraph, or any combination of suitable paragraphs, wherein the nucleic acid is DNA. 253. The method of paragraph 250, any other suitable paragraph, or any combination of suitable paragraphs, wherein the nucleic acid is RNA. 254. The method of paragraph 250, any other suitable paragraph, or any combination of suitable paragraphs, wherein the nucleic acid is a combination of DNA and RNA. 255. The method of clause 250, any other suitable clause, or any combination of suitable clauses, wherein inflammation is associated with the disease. 256. The method of clause 255, any other suitable clause, or any combination of suitable clauses, wherein the disease is inflammatory bowel disease (IBD). 257. The method of clause 255, any other suitable clause, or any combination of suitable clauses, wherein the disease is ulcerative colitis (UC). 258. The method of clause 255, any other suitable clause, or any combination of suitable clauses, wherein the disease is Crohn's disease (CD). 259. The method of clause 250, any other suitable clause, or any combination of suitable clauses, wherein assessing inflammation comprises assessing disease activity in the subject. 260. The method of clause 259, any other suitable clause, or any combination of suitable clauses, wherein the assessment is a determination of active IBD symptoms in the subject. 261. The method of clause 260, any other suitable clause, or any combination of suitable clauses, wherein the determination of active IBD symptoms indicates mild IBD symptoms. 262. The method of clause 260, any other suitable clause, or any combination of suitable clauses, wherein the determination of active IBD symptoms indicates moderate IBD symptoms. 263. The method of clause 260, any other suitable clause, or any combination of suitable clauses, wherein the determination of active IBD symptoms indicates severe IBD symptoms. 264. The method of clause 259, any other suitable clause, or any combination of suitable clauses, wherein the assessment is a determination of IBD remission in the subject. 265. The method of clause 250, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 1. 266. The method of clause 250, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 2. 267. The method of clause 250, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 3. 268. The method of clause 250, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 4. 269. The method of paragraph 250, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise a combination of biomarkers listed in Table 5. 270. The method of paragraph 250, any other suitable paragraph, or any combination of suitable paragraphs, wherein the one or more stool-derived eukaryotic nucleic acid biomarkers comprise a stool-derived eukaryotic RNA biomarker. 271. The method of paragraph 270, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers include enterocyte-specific biomarkers. 272. The method of paragraph 270, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist essentially of enterocyte-specific biomarkers. 273. The method of paragraph 270, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist of enterocyte-specific biomarkers. 274. The method of paragraph 270, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers include lymphocyte-specific biomarkers. 275. The method of paragraph 270, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist essentially of lymphocyte-specific biomarkers. 276. The method of paragraph 270, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist of lymphocyte-specific biomarkers. 277. The method of paragraph 270, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers include enterocyte-specific biomarkers and lymphocyte-specific biomarkers. 278. The method of paragraph 270, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist essentially of enterocyte-specific biomarkers and lymphocyte-specific biomarkers. 279. The method of paragraph 270, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist of enterocyte-specific biomarkers and lymphocyte-specific biomarkers. 280. The method of paragraph 270, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers include one or more non-therapeutic targets. 281. The method of paragraph 280, any other suitable paragraph, or any combination of suitable paragraphs, wherein the one or more non-therapeutic targets are selected from the group consisting of RNA transcripts that mediate cytoskeletal remodeling, proliferation, and inflammatory responses. 282. The method of paragraph 270, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers comprise one or more therapeutic targets. 283. The method of paragraph 282, any other suitable clause, or any combination of suitable clauses, wherein the one or more therapeutic targets are selected from the group consisting of TNF, MADCAM1, ITGA4, JAK1, TYK2, IL-12, IL-23, and any combination thereof. 284. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TNF. 285. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is MADCAM1. 286. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is ITGA4. 287. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is JAK1. 288. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TYK2. 289. The method of paragraph 282, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is IL-12. 290. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-23. 291. The method of clause 282, any other suitable clause, or any combination of suitable clauses, wherein the one or more therapeutic targets are selected from the group consisting of a4B7, CCR6, CD30 ligand, FPR1, GLP-2, IL-2, IL-4 / IL-13, IL7R, IL-10, IL-12 / IL-23, IL-36, JAK, JAK1, JAK(ITK / TXK / JAK3), JAK3 / TEC, MC1r, MRP2, NLRP3 inflammasome, NLRX1, PDE4, PSGL-1, RIPK1, S1P1, TL1A, TLR9, TNFα, TNFSF15, TPL2, TREM1, TYK2, and any combination thereof. 292. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is a4B7. 293. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is CCR6. 294. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is CD30 ligand. 295. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is FPR1. 296. The method of paragraph 282, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is GLP-2. 297. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-2. 298. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-4 / IL-13. 299. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL7R. 300. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-10. 301. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-12 / IL-23. 302. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-36. 303. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is JAK. 304. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is JAK1. 305. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is JAK (ITK / TXK / JAK3). 306. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is JAK3 / TEC. 307. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is MC1r. 308. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is MRP2. 309. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is the NLRP3 inflammasome. 310. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is NLRX1. 311. The method of paragraph 282, any other suitable clause, or any combination of suitable clauses, wherein the therapeutic target is PDE4. 312. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is PSGL-1. 313. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is RIPK1. 314. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is S1P1. 315. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TL1A. 316. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TLR9. 317. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TNFα. 318. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TNFSF15. 319. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TPL2. 320. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TREM1. 321. The method of paragraph 282, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TYK2. 322. The method of clause 250, any other suitable clause, or any combination of suitable clauses, wherein the assessment includes monitoring mucosal lesions in the subject. 323. The method of clause 250, any other suitable clause, or any combination of suitable clauses, wherein assessing includes assessing inflammation in the subject. 324. The method of paragraph 323, any other suitable paragraph, or any combination of suitable paragraphs, wherein assessing inflammation includes analyzing the amount of inflammation. 325. The method of paragraph 323, any other suitable paragraph, or any combination of suitable paragraphs, wherein assessing inflammation includes analyzing increases or decreases in inflammation. 326. The method of paragraph 323, any other suitable paragraph, or any combination of suitable paragraphs, wherein assessing inflammation includes analyzing changes in inflammation. 327. The method of clause 250, any other suitable clause, or any combination of suitable clauses, wherein the assessment includes assessment of cell types in the subject. 328. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the evaluation includes analysis of the abundance of cell types. 329. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the evaluation comprises analysis of cell type gain or loss. 330. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the evaluation comprises analysis of changes in the relative proportions of cell types. 331. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is an inflammatory cell. 332. The method of clause 327, any other suitable clause, or any combination of suitable clauses, wherein the cell type is an immunogenic cell. 333. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is an intestinal cell. 334. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is an enterocyte-related cell. 335. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a lymphocyte cell. 336. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a lymphocyte-related cell. 337. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a T cell. 338. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a NK cell. 339. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a B cell. 340. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a macrophage. 341. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a neutrophil. 342. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is an endothelial cell. 343. The method of paragraph 327, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a fibroblast. 344. The method of clause 250, any other suitable clause, or any combination of suitable clauses, wherein the assessment comprises a prognosis of a treatment response to a medical intervention in the subject. 345. The method of paragraph 344, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical intervention is a drug therapy. 346. The method of clause 345, any other suitable clause, or any combination of suitable clauses, wherein the medication is an IBD medication. 347. The method of paragraph 345, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication is a UC medication. 348. The method of clause 345, any other suitable clause, or any combination of suitable clauses, wherein the medication is a CD medication. 349. The method of clause 345, any other suitable clause, or any combination of suitable clauses, wherein the medication comprises an anti-inflammatory drug. 350. The method of paragraph 345, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication comprises an immune system suppressant. 351. The method of paragraph 345, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical therapy includes a biologic. 352. The method of paragraph 345, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical therapy includes an antibiotic. 353. The method of clause 344, any other suitable clause, or any combination of suitable clauses, wherein the medical intervention is a colonoscopy. 354. The method of paragraph 250, any other suitable paragraph, or any combination of suitable paragraphs, wherein the evaluation comprises determining the therapeutic effectiveness of a medical intervention in the subject. 355. The method of paragraph 354, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical intervention is a drug therapy. 356. The method of paragraph 355, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication is an IBD medication. 357. The method of paragraph 355, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication is a UC medication. 358. The method of paragraph 355, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication is a CD medication. 359. The method of paragraph 355, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication comprises an anti-inflammatory drug. 360. The method of paragraph 355, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication comprises an immune system suppressant. 361. The method of paragraph 355, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical therapy includes a biologic. 362. The method of paragraph 355, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical therapy includes an antibiotic. 363. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the medical intervention is a colonoscopy. 364. The method of paragraph 250, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring the expression level of the nucleic acid biomarker comprises extracting nucleic acid from a eukaryotic cell. 365. The method of paragraph 250, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring the expression level of the nucleic acid biomarker comprises extracting DNA from eukaryotic cells. 366. The method of paragraph 250, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring expression levels of nucleic acid biomarkers comprises RNA extraction from eukaryotic cells. 367. The method of paragraph 250, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring expression levels of nucleic acid biomarkers comprises next generation sequencing. 368.c) The method of clause 250, any other suitable clause, or any combination of suitable clauses, further comprising the step of diagnosing the disease in the subject. 369. The method of clause 368, any other suitable clause, or any combination of suitable clauses, wherein the disease is inflammatory bowel disease (IBD). 370. The method of clause 368, any other suitable clause, or any combination of suitable clauses, wherein the disease is ulcerative colitis (UC). 371. The method of clause 368, any other suitable clause, or any combination of suitable clauses, wherein the disease is Crohn's disease (CD). 372.c) The method of clause 250, any other suitable clause, or any combination of suitable clauses, further comprising treating a disease in the subject. 373. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the disease is inflammatory bowel disease (IBD). 374. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the disease is ulcerative colitis (UC). 375. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the disease is Crohn's disease (CD). 376. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject an IBD medication. 377. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject a UC medication. 378. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject a CD medication. 379. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject an anti-inflammatory drug. 380. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject an immune system suppressant. 381. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject a biologic. 382. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering an antibiotic to the subject. 383. A method for assessing one or more immune cells in a subject, comprising: measuring the expression level of one or more stool-derived eukaryotic nucleic acid biomarkers selected from the biomarkers described herein in eukaryotic nucleic acid extracted from a stool sample from the subject; Including, The method, wherein the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample indicates an assessment of one or more immune cells in the subject. 384. The method of clause 383, any other suitable clause, or any combination of suitable clauses, comprising comparing the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in a stool sample with the measured expression level of one or more stool-derived eukaryotic nucleic acid biomarkers in a control, wherein a difference in the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample relative to the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the control indicates an assessment of immune cells in the subject. 385. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein the nucleic acid is DNA. 386. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein the nucleic acid is RNA. 387. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein the nucleic acid is a combination of DNA and RNA. 388. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein the immune cells are associated with the disease. 389. The method of clause 388, any other suitable clause, or any combination of suitable clauses, wherein the disease is inflammatory bowel disease (IBD). 390. The method of clause 388, any other suitable clause, or any combination of suitable clauses, wherein the disease is ulcerative colitis (UC). 391. The method of clause 388, any other suitable clause, or any combination of suitable clauses, wherein the disease is Crohn's disease (CD). 392. The method of clause 383, any other suitable clause, or any combination of suitable clauses, wherein assessing immune cells comprises assessing disease activity in the subject. 393. The method of clause 392, any other suitable clause, or any combination of suitable clauses, wherein the assessment is a determination of active IBD symptoms in the subject. 394. The method of clause 393, any other suitable clause, or any combination of suitable clauses, wherein the determination of active IBD symptoms indicates mild IBD symptoms. 395. The method of clause 393, any other suitable clause, or any combination of suitable clauses, wherein the determination of active IBD symptoms indicates moderate IBD symptoms. 396. The method of clause 393, any other suitable clause, or any combination of suitable clauses, wherein the determination of active IBD symptoms indicates severe IBD symptoms. 397. The method of paragraph 392, any other suitable paragraph, or any combination of suitable paragraphs, wherein the assessment is a determination of IBD remission in the subject. 398. The method of clause 383, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 1. 399. The method of clause 383, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 2. 400. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 3. 401. The method of clause 383, any other suitable clause, or any combination of suitable clauses, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 4. 402. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise a combination of biomarkers listed in Table 5. 403. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein the one or more stool-derived eukaryotic nucleic acid biomarkers comprise stool-derived eukaryotic RNA biomarkers. 404. The method of paragraph 403, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers include enterocyte-specific biomarkers. 405. The method of paragraph 403, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist essentially of enterocyte-specific biomarkers. 406. The method of paragraph 403, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist of enterocyte-specific biomarkers. 407. The method of paragraph 403, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers include lymphocyte-specific biomarkers. 408. The method of paragraph 403, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist essentially of lymphocyte-specific biomarkers. 409. The method of paragraph 403, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist of lymphocyte-specific biomarkers. 410. The method of paragraph 403, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers include enterocyte-specific biomarkers and lymphocyte-specific biomarkers. 411. The method of paragraph 403, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist essentially of enterocyte-specific biomarkers and lymphocyte-specific biomarkers. 412. The method of paragraph 403, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers consist of enterocyte-specific biomarkers and lymphocyte-specific biomarkers. 413. The method of paragraph 403, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers include one or more non-therapeutic targets. 414. The method of paragraph 413, any other suitable paragraph, or any combination of suitable paragraphs, wherein the one or more non-therapeutic targets are selected from the group consisting of RNA transcripts that mediate cytoskeletal remodeling, proliferation, and inflammatory responses. 415. The method of paragraph 403, any other suitable paragraph, or any combination of suitable paragraphs, wherein the stool-derived eukaryotic RNA biomarkers comprise one or more therapeutic targets. 416. The method of clause 415, any other suitable clause, or any combination of suitable clauses, wherein the one or more therapeutic targets are selected from the group consisting of TNF, MADCAM1, ITGA4, JAK1, TYK2, IL-12, IL-23, and any combination thereof. 417. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TNF. 418. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is MADCAM1. 419. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is ITGA4. 420. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is JAK1. 421. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TYK2. 422. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-12. 423. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-23. 424. The method of clause 415, any other suitable clause, or any combination of suitable clauses, wherein the one or more therapeutic targets are selected from the group consisting of a4B7, CCR6, CD30 ligand, FPR1, GLP-2, IL-2, IL-4 / IL-13, IL7R, IL-10, IL-12 / IL-23, IL-36, JAK, JAK1, JAK(ITK / TXK / JAK3), JAK3 / TEC, MC1r, MRP2, NLRP3 inflammasome, NLRX1, PDE4, PSGL-1, RIPK1, S1P1, TL1A, TLR9, TNFα, TNFSF15, TPL2, TREM1, TYK2, and any combination thereof. 425. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is a4B7. 426. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is CCR6. 427. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is CD30 ligand. 428. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is FPR1. 429. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is GLP-2. 430. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-2. 431. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-4 / IL-13. 432. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL7R. 433. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-10. 434. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-12 / IL-23. 435. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is IL-36. 436. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is JAK. 437. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is JAK1. 438. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is JAK (ITK / TXK / JAK3). 439. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is JAK3 / TEC. 440. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is MC1r. 441. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is MRP2. 442. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is the NLRP3 inflammasome. 443. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is NLRX1. 444. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is PDE4. 445. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is PSGL-1. 446. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is RIPK1. 447. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is S1P1. 448. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TL1A. 449. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TLR9. 450. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TNFα. 451. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TNFSF15. 452. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TPL2. 453. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TREM1. 454. The method of paragraph 415, any other suitable paragraph, or any combination of suitable paragraphs, wherein the therapeutic target is TYK2. 455. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein the assessment includes monitoring mucosal lesions in the subject. 456. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein assessing includes assessing inflammation in the subject. 457. The method of paragraph 456, any other suitable paragraph, or any combination of suitable paragraphs, wherein assessing inflammation includes analyzing the amount of inflammation. 458. The method of paragraph 456, any other suitable paragraph, or any combination of suitable paragraphs, wherein assessing inflammation includes analyzing increases or decreases in inflammation. 459. The method of paragraph 456, any other suitable paragraph, or any combination of suitable paragraphs, wherein assessing inflammation includes analyzing changes in inflammation. 460. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein the evaluation includes evaluation of cell types in the subject. 461. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the evaluation includes analysis of the abundance of cell types. 462. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the evaluation includes analysis of cell type gain or loss. 463. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the evaluation comprises analysis of changes in the relative proportions of cell types. 464. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is an inflammatory cell. 465. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is an immunogenic cell. 466. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is an intestinal cell. 467. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is an enterocyte-related cell. 468. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a lymphocyte cell. 469. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a lymphocyte-related cell. 470. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a T cell. 471. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a NK cell. 472. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a B cell. 473. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a macrophage. 474. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a neutrophil. 475. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is an endothelial cell. 476. The method of paragraph 460, any other suitable paragraph, or any combination of suitable paragraphs, wherein the cell type is a fibroblast. 477. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein the assessment is prognostic of a treatment response to a medical intervention in the subject. 478. The method of paragraph 477, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical intervention is a drug therapy. 479. The method of paragraph 478, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication is an IBD medication. 480. The method of paragraph 478, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication is a UC medication. 481. The method of paragraph 478, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication is a CD medication. 482. The method of paragraph 478, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication comprises an anti-inflammatory drug. 483. The method of paragraph 478, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication comprises an immune system suppressant. 484. The method of paragraph 478, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical therapy includes a biologic. 485. The method of paragraph 478, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical therapy includes an antibiotic. 486. The method of paragraph 477, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical intervention is a colonoscopy. 487. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein the assessment is a determination of the therapeutic effectiveness of a medical intervention in the subject. 488. The method of paragraph 487, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical intervention is a drug therapy. 489. The method of paragraph 488, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication is an IBD medication. 490. The method of paragraph 488, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication is a UC medication. 491. The method of paragraph 488, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication is a CD medication. 492. The method of paragraph 488, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication comprises an anti-inflammatory drug. 493. The method of paragraph 488, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medication comprises an immune system suppressant. 494. The method of paragraph 488, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical therapy includes a biologic. 495. The method of paragraph 488, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical therapy includes an antibiotic. 496. The method of paragraph 487, any other suitable paragraph, or any combination of suitable paragraphs, wherein the medical intervention is a colonoscopy. 497. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring the expression level of the nucleic acid biomarker comprises extracting nucleic acid from a eukaryotic cell. 498. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring the expression level of the nucleic acid biomarker comprises extracting DNA from the eukaryotic cell. 499. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring the expression level of the nucleic acid biomarker comprises RNA extraction from eukaryotic cells. 500. The method of paragraph 383, any other suitable paragraph, or any combination of suitable paragraphs, wherein measuring the expression levels of the nucleic acid biomarkers comprises next generation sequencing. 501.c) The method of clause 383, any other suitable clause, or any combination of suitable clauses, further comprising the step of diagnosing the disease in the subject. 502. The method of clause 501, any other suitable clause, or any combination of suitable clauses, wherein the disease is inflammatory bowel disease (IBD). 503. The method of clause 501, any other suitable clause, or any combination of suitable clauses, wherein the disease is ulcerative colitis (UC). 504. The method of clause 501, any other suitable clause, or any combination of suitable clauses, wherein the disease is Crohn's disease (CD). 505.c) The method of clause 383, any other suitable clause, or any combination of suitable clauses, further comprising treating a disease in a subject. 506. The method of clause 505, any other suitable clause, or any combination of suitable clauses, wherein the disease is inflammatory bowel disease (IBD). 507. The method of clause 505, any other suitable clause, or any combination of suitable clauses, wherein the disease is ulcerative colitis (UC). 508. The method of clause 505, any other suitable clause, or any combination of suitable clauses, wherein the disease is Crohn's disease (CD). 509. The method of clause 505, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject an IBD medication. 510. The method of clause 505, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject a UC medication. 511. The method of clause 505, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject a CD medication. 512. The method of clause 505, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject an anti-inflammatory drug. 513. The method of clause 505, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject an immune system suppressant. 514. The method of clause 505, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering to the subject a biologic. 515. The method of clause 505, any other suitable clause, or any combination of suitable clauses, wherein treating the disease comprises administering an antibiotic to the subject. [Example]
[0094] Example 1 Analysis of seRNA in Crohn's disease subjects Stool samples were collected from 68 individuals and followed at up to three time points during routine clinic visits, before and after the initiation of advanced treatment. Stool samples underwent RNA extraction and sequencing using a custom capture panel (n = 1,507 transcripts). When available, stool-derived eukaryotic RNA (seRNA) signatures were compared with CD Activity Index (CDAI) scores and endoscopy. Random forest models were constructed to assess their ability to classify disease severity compared with CDAI scores. Furthermore, seRNA signatures were also used to assess therapeutic target expression and cell type abundance at various time points.
[0095] Across 102 samples from 68 individuals, a random forest classifier successfully distinguished individuals with active disease (n = 37) from those in remission (n = 65) with 81% accuracy. The machine learning model was constructed using 5-fold internal cross-validation. As shown in Figure 1A, classifier 1 predicted the Crohn's Disease Activity Index (CDAI) for subjects with active disease (n = 37) compared with subjects in remission (n = 65). As shown in Figure 1B, classifier 2 further distinguished subjects with mild disease (n = 16) from those with moderate disease (n = 22). For each classifier, the top three biomarker features are shown. Each row in the heatmap represents a composite biomarker consisting of the transcripts highlighted in that row. Color highlighting indicates transcript expression. The gene ontology for each transcript is also presented.
[0096] A second classifier was utilized for subjects with active (mild or moderate) disease (n=37). This classifier successfully separated individuals with mild disease (n=15) from those with moderate disease (n=22) with 92% accuracy. In 16 subjects with longitudinal data, in responders whose lymphocyte signatures declined during treatment, pretreatment seRNA signatures with either vedolizumab, ustekinumab, or infliximab showed high expression of relevant therapeutic targets (e.g., ITGA4 / ITGB7 for vedolizumab, IL12A / IL12B / IL23A for ustekinumab, or TNF for infliximab) at TO.
[0097] Figures 2A-2C show various subjects treated with vedolizumab, ustekinumab, and infliximab, respectively. For each subject, the boxes in the first column represent the expression of transcripts associated with the therapeutic target, pathways of the therapeutic target, or receptors associated with the therapy. The boxes in the second column present the expression of various lymphocytes or stromal cells (i.e., cell type deconvolution). For each subject, the number of rows corresponds to the number of longitudinal samples evaluated, ordered chronologically with the first box representing the earliest time point and subsequent boxes representing later time points. Target expression and cell type deconvolution are presented at multiple time points to show changes in expression over the course of treatment. Certain boxes with darker shades represent increases in normalized expression.
[0098] Example 2 Alternative analysis of seRNA in Crohn's disease subjects Stool samples can be collected from subjects with Crohn's disease who are being evaluated for a treatment. By way of example, subjects can be randomized into a drug treatment group and a placebo (control) group. Subjects can be evaluated for efficacy, safety, and / or tolerability of the drug treatment compared to placebo according to this example.
[0099] Patients can be evaluated for clinical response, endoscopic response, laboratory outcome, and / or histological evaluation. In the study, stool samples can be collected from subjects before, during, and / or after completing drug or placebo treatment.
[0100] Stool samples can be subjected to seRNA extraction and sequencing to evaluate transcriptome changes associated with drug treatment and treatment response.For example, stool samples collected from subjects can be subjected to total RNA extraction and / or next-generation sequencing according to conventional methods.Sequencing data can be compared with one or more of clinical response, endoscopic response, clinical outcome, and / or histological evaluation.
[0101] Example 3 Analysis of seRNA in ulcerative colitis subjects Stool samples were obtained from 15 subjects with active ulcerative colitis (UC) and 15 healthy volunteers. The diagnosis of UC was confirmed by recent endoscopy or based on patients with no history of the disease. Stool samples were collected and frozen with or without a stabilizing buffer prior to analysis. Samples were thawed and subjected to parallel evaluation of both protein and nucleic acid. Protein evaluation was performed by ELISA assay to quantify human calprotectin in the samples. Each stool sample was subjected to calprotectin quantification by ELISA in duplicate. Nucleic acid evaluation was performed by eukaryotic RNA extraction, RNA quality control evaluation, library preparation, hybridization capture, and whole transcriptome sequencing.
[0102] The log2 mean concentrations of ELISA calprotectin assays were compared to total S100A8 or S100A9 concentrations (calprotectin subunit transcripts) normalized to total read counts. Figure 3 shows protein-based calprotectin measurements (ELISA assay) compared to RNA-based calprotectin measurements (whole transcriptome sequencing). As shown in Figure 3, significant elevations were observed in both protein-based and RNA-based calprotectin measurements when individuals with ulcerative colitis (UC) were compared to healthy volunteers. A correlation existed between protein-based and RNA-based calprotectin measurements. Sensitivity for RNA-based measurements correlated with the ability to measure housekeeping transcript concentrations and total read counts. For example, UC subjects with low GAPDH read counts (red dots on the scatter plot) had lower normalized RNA-based calprotectin measurements.
[0103] Figure 4 shows a receiver operating characteristic (ROC) plot, demonstrating a reduced area under the curve (AUC) with the protein-based method versus the RNA-based method (0.824 vs. 0.879). When assessing the optimum on the ROC AUC for both the protein-based and RNA-based calprotectin measurements, the RNA-based measurement demonstrated a higher level of specificity.
[0104] Example 4 Analysis of RNA and FIT in patients with IBD Twelve individuals with inflammatory bowel disease underwent fecal immunochemical testing before undergoing standard-of-care colonoscopy. Stool samples were mailed at ambient temperature for up to 96 hours. Stool samples were subjected to RNA extraction, quality assessment, and digital droplet PCR. Eight RNA transcripts were examined to assess the presence of colorectal cancer and advanced adenomas. These transcripts, demographic information, and FIT results were evaluated by an algorithm to determine positive or negative results. Of the 12 subjects, three had other precancerous lesions on colonoscopy, seven had hyperplastic polyps on colonoscopy, and two had no colonoscopy findings. Of the three subjects with adenomas, one had a positive RNA-FIT result. Of the seven subjects with hyperplastic polyps, four had a positive RNA-FIT result. Of the two patients without colonoscopy findings, both had negative RNA-FIT results.
Claims
1. 1. A method for assessing a disease in a subject, comprising: measuring the expression level of one or more stool-derived eukaryotic nucleic acid biomarkers selected from the biomarkers described herein in eukaryotic nucleic acid extracted from a stool sample from said subject. Including, wherein the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample is indicative of the assessment of disease in the subject.
2. 10. The method of claim 1, comprising comparing the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the stool sample with the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in a control, wherein a difference in the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the stool sample relative to the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the control indicates the assessment of disease in the subject.
3. The method of claim 1, wherein the nucleic acid is DNA.
4. The method of claim 1, wherein the nucleic acid is RNA.
5. 2. The method of claim 1, wherein the disease is inflammatory bowel disease (IBD).
6. 2. The method of claim 1, wherein the disease is ulcerative colitis (UC).
7. 2. The method of claim 1, wherein the disease is Crohn's disease (CD).
8. 10. The method of claim 1, wherein said assessment of disease comprises assessment of disease activity in said subject.
9. 2. The method of claim 1, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 1.
10. 2. The method of claim 1, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 2.
11. 2. The method of claim 1, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 3.
12. 2. The method of claim 1, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 4.
13. 2. The method of claim 1, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise a combination of biomarkers listed in Table 5.
14. 2. The method of claim 1, wherein the one or more stool-derived eukaryotic nucleic acid biomarkers comprise stool-derived eukaryotic RNA biomarkers, and the stool-derived eukaryotic RNA biomarkers comprise one or more therapeutic targets.
15. The method of claim 1 , wherein the assessment comprises assessing inflammation in the subject.
16. The method of claim 1 , wherein said evaluation comprises evaluation of a cell type in said subject.
17. 10. The method of claim 1, further comprising diagnosing a disease in the subject, wherein the disease is inflammatory bowel disease (IBD).
18. 10. The method of claim 1, further comprising diagnosing a disease in the subject, wherein the disease is ulcerative colitis (UC).
19. 10. The method of claim 1, further comprising diagnosing a disease in the subject, wherein the disease is Crohn's disease (CD).
20. 1. A method for predicting a therapeutic response to a disease in a subject, comprising: measuring the expression level of one or more stool-derived eukaryotic nucleic acid biomarkers selected from the biomarkers described herein in eukaryotic nucleic acid extracted from a stool sample from said subject. Including, The method, wherein the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample is indicative of a treatment response for the disease in the subject.
21. 21. The method of claim 20, comprising comparing the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the stool sample with the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in a control, wherein a difference in the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the stool sample relative to the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the control indicates a treatment response for the disease in the subject.
22. 21. The method of claim 20, wherein the nucleic acid is DNA.
23. 21. The method of claim 20, wherein the nucleic acid is RNA.
24. 21. The method of claim 20, wherein the disease is inflammatory bowel disease (IBD).
25. 21. The method of claim 20, wherein the disease is ulcerative colitis (UC).
26. 21. The method of claim 20, wherein the disease is Crohn's disease (CD).
27. 21. The method of claim 20, wherein the therapeutic response comprises an assessment of disease activity in the subject.
28. 21. The method of claim 20, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 1.
29. 21. The method of claim 20, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 2.
30. 21. The method of claim 20, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 3.
31. 21. The method of claim 20, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 4.
32. 21. The method of claim 20, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise a combination of biomarkers listed in Table 5.
33. 21. The method of claim 20, wherein said assessment comprises assessment of inflammation in said subject.
34. 21. The method of claim 20, wherein said evaluating comprises evaluating a cell type in said subject.
35. 21. The method of claim 20, wherein the therapeutic response is a response to a medical intervention in the subject.
36. 21. The method of claim 20, further comprising the step of c) treating the disease in the subject.
37. 37. The method of claim 36, wherein the disease is inflammatory bowel disease (IBD).
38. 37. The method of claim 36, wherein the disease is ulcerative colitis (UC).
39. 37. The method of claim 36, wherein the disease is Crohn's disease (CD).
40. 1. A method for assessing inflammation in a subject, comprising: measuring the expression level of one or more stool-derived eukaryotic nucleic acid biomarkers selected from the biomarkers described herein in eukaryotic nucleic acid extracted from a stool sample from said subject. Including, wherein the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample is indicative of the assessment of inflammation in the subject.
41. 41. The method of Claim 40, comprising comparing the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the stool sample with the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in a control, wherein a difference in the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the stool sample relative to the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the control indicates the assessment of inflammation in the subject.
42. 41. The method of claim 40, wherein the nucleic acid is DNA.
43. 41. The method of claim 40, wherein the nucleic acid is RNA.
44. 41. The method of claim 40, wherein the inflammation is associated with a disease, and the disease is inflammatory bowel disease (IBD).
45. 41. The method of claim 40, wherein the inflammation is associated with a disease, and the disease is ulcerative colitis (UC).
46. 41. The method of claim 40, wherein the inflammation is associated with a disease, and the disease is Crohn's disease (CD).
47. 41. The method of claim 40, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 1.
48. 41. The method of claim 40, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 2.
49. 41. The method of claim 40, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 3.
50. 41. The method of claim 40, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 4.
51. 41. The method of claim 40, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise a combination of biomarkers listed in Table 5.
52. 41. The method of claim 40, wherein said one or more stool-derived eukaryotic nucleic acid biomarkers comprise stool-derived eukaryotic RNA biomarkers, and said stool-derived eukaryotic RNA biomarkers comprise one or more therapeutic targets.
53. 41. The method of claim 40, wherein said evaluating comprises evaluating a cell type in said subject.
54. 41. The method of claim 40, wherein the evaluation comprises a prognosis of a therapeutic response to a medical intervention in the subject.
55. 41. The method of claim 40, wherein said evaluation comprises determining the therapeutic efficacy of a medical intervention in said subject.
56. 41. The method of claim 40, further comprising the step of c) diagnosing a disease in the subject, wherein the disease is inflammatory bowel disease (IBD).
57. 41. The method of claim 40, further comprising the step of c) diagnosing a disease in the subject, wherein the disease is ulcerative colitis (UC).
58. 41. The method of claim 40, further comprising the step of c) diagnosing a disease in the subject, wherein the disease is Crohn's disease (CD).
59. 41. The method of claim 40, further comprising the step of c) treating a disease in the subject, wherein the disease is inflammatory bowel disease (IBD).
60. 41. The method of claim 40, further comprising the step of c) treating a disease in the subject, wherein the disease is ulcerative colitis (UC).
61. 41. The method of claim 40, further comprising the step of c) treating a disease in the subject, wherein the disease is Crohn's disease (CD).
62. 1. A method for assessing one or more immune cells in a subject, comprising: measuring the expression level of one or more stool-derived eukaryotic nucleic acid biomarkers selected from the biomarkers described herein in eukaryotic nucleic acid extracted from a stool sample from said subject. Including, wherein the measured expression level of the one or more stool-derived eukaryotic nucleic acid biomarkers in the stool sample is indicative of the assessment of the one or more immune cells in the subject.
63. 63. The method of Claim 62, comprising comparing the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the stool sample with the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in a control, wherein a difference in the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the stool sample relative to the measured expression levels of the one or more fecal-derived eukaryotic nucleic acid biomarkers in the control indicates said assessment of the immune cells in the subject.
64. 63. The method of claim 62, wherein the nucleic acid is DNA.
65. 63. The method of claim 62, wherein the nucleic acid is RNA.
66. 63. The method of claim 62, wherein said evaluation of immune cells comprises evaluation of disease activity in said subject.
67. 67. The method of claim 66, wherein said assessment is a determination of active IBD symptoms in said subject.
68. 67. The method of claim 66, wherein the evaluation is a determination of IBD remission in the subject.
69. 63. The method of claim 62, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 1.
70. 63. The method of claim 62, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 2.
71. 63. The method of claim 62, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 3.
72. 63. The method of claim 62, wherein the stool-derived eukaryotic nucleic acid biomarkers comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 biomarkers selected from the biomarkers listed in Table 4.
73. 63. The method of Claim 62, wherein said stool-derived eukaryotic nucleic acid biomarkers comprise a combination of biomarkers listed in Table 5.
74. 63. The method of Claim 62, wherein said one or more stool-derived eukaryotic nucleic acid biomarkers comprise stool-derived eukaryotic RNA biomarkers, and said stool-derived eukaryotic RNA biomarkers comprise one or more non-therapeutic targets.
75. 63. The method of claim 62, wherein the evaluation comprises monitoring mucosal lesions in the subject.
76. 63. The method of claim 62, wherein said assessment comprises assessment of inflammation in said subject.
77. 63. The method of claim 62, wherein said evaluating comprises evaluating a cell type in said subject.
78. 63. The method of claim 62, wherein said assessment is prognostic of a therapeutic response to a medical intervention in said subject.
79. 63. The method of claim 62, wherein said evaluation is a determination of therapeutic efficacy of a medical intervention in said subject.
Citation Information
Patent Citations
Detection method
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