Methods, systems, and kits for treatment of inflammatory diseases by targeting tl1a

Abstract

Provided are methods, systems, and kits for selecting a subject for treatment with an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression based on the ratio between the TL1A isoforms.

Description

25743 METHODS, SYSTEMS, AND KITS FOR TREATMENT OF INFLAMMATORY DISEASES BY TARGETING TL1A CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 504,540 filed May 26, 2023, the entire contents of which are incorporated by reference herein. REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. The XML file, created on May 23, 2024, is named 25743-WO-PCT_SL.xml and is 1,346,000 bytes in size. 1. BACKGROUND

[0003] Inflammatory disease, fibrostenotic disease, and fibrotic disease pose a significant health burden worldwide due to the vast number of individuals affected and heterogeneous disease pathogenesis and varied clinical manifestations. One such disease is inflammatory bowel disease (IBD), which has two common forms, Crohn’s disease (CD) and ulcerative colitis (UC). IBD is the chronic, relapsing inflammatory disorders of the gastrointestinal tract. Incidences of IBD are prevalent, affecting nearly three million individuals in the United States alone.

[0004] Few treatment options are available to patients that suffer from inflammatory disease, fibrostenotic disease, and fibrotic disease. Existing anti-inflammatory therapy such as steroids and tumor necrosis factor (TNF) inhibitors are typically used as a first line treatment for treating IBD. Unfortunately, a significant number of patients experience a lack of response or a loss of response to existing anti-inflammatory therapies, especially TNF inhibitors. While the patient is treated with an anti-inflammatory therapy that is ineffective, the disease worsens. Surgery, in the form of structureplasty (reshaping of the intestine) or resection (removal of the intestine), is the only treatment option for patients that do not respond to first line therapies. Surgical treatments for IBD are invasive, causing post-operative risks for an estimated third of patients undergoing surgery, such as anastomotic leak, infection, and bleeding.

[0005] The pathogenesis of inflammatory disease, fibrostenotic disease, and fibrotic disease, like IBD, is thought to involve an uncontrolled immune response that may be triggered by certain environmental factors in a genetically susceptible individual. The heterogeneity of diseasepathogenesis and clinical course, combined with the variable response to treatment and its associated side effects, suggests a personalized medicine approach to treating these diseases is the best treatment strategy. Yet there are very few personalized therapies available to patients. Accordingly, there is a need to identify targeted therapeutic approaches f or the treatment of inflammatory disease, fibrostenotic disease, and fibrotic disease and subclinical phenotypes thereof, and an even greater need to develop reliable methodology to identifying patients who may respond to any given therapeutic approach. The needed methodologies would also identify subjects not yet diagnosed who are at risk of developing the disease, for which preventative interventions could be prescribed to reduce the growing health burden. 2. SUMMARY

[0006] The TL1A isoform ratios, proxy markers, and CDx models based on them described herein are associated (individually or together) with (i) an increase in a level of TNFSF15 (TL1A) protein expression in a sample obtained from a subject or patient, as compared to a reference level of TNFSF15 (TL1A) protein expression (e.g., derived from a normal individual), and / or (ii) an increase of a positive therapeutic response in IBD patients to a treatment with the TL1A inhibitor as compared to the reference level of response in patients not selected by the TL1A isoform ratios, proxy markers, and CDx models. More specifically, the TL1A isoform ratios, proxy markers, and CDx models based on them described herein are associated (individually or together) with (i) alone; (ii) alone; or (i) and (ii) together, wherein (i) and (ii) corresponds to the (i) and (ii) numbered items in the previous clause of this paragraph. Accordingly and as an example, the TL1A isoform ratios, proxy markers, and CDx models based on them described herein are associated with an increase in a level of TNFSF15 (TL1A) protein expression in a sample obtained from a subject or patient, as compared to a reference level of TNFSF15 (TL1A) protein expression (e.g., derived from a normal individual). Additionally, the TL1A isoform ratios, proxy markers, and CDx models based on them described herein are associated) with an increase of a positive therapeutic response in IBD patients to a treatment with the inhibitor of TL1A activity or expression, as compared to the reference level of response in patients not selected by the TL1A isoform ratios, proxy markers, and CDx models. The patient may be diagnosed with IBD, CD, or both. The subject may be suspected of having IBD, CD, or both.

[0007] In one aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, wherein the subject is selected based on a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof.

[0008] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) subjecting the sample to an assay adapted to determine a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof; (iii) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the TL1A isoform ratio or the proxy marker; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0009] In a further aspect, provided herein is a method of determining a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”) or a proxy marker having a statistically significant correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; and (c) determining a ratio TL1A isoform ratio, a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the TL1A isoform ratio or the proxy marker.

[0010] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; (c) determining aratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof; and (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the TL1A isoform ratio or the proxy marker.

[0011] In some embodiments, the method further comprises preparing nucleic acids from the sample.

[0012] In some embodiments, the correlation is Pearson correlation or Spearman correlation. In some embodiments, the correlation has a correlation coefficient with an absolute value of at least about 0.30, at least about 0.31, at least about 0.32, at least about 0.33, at least about 0.34, at least about 0.35, at least about 0.36, at least about 0.37, at least about 0.38, at least about 0.39, at least about 0.40, at least about 0.41, at least about 0.42, at least about 0.43, at least about 0.44, at least about 0.45, at least about 0.46, at least about 0.47, at least about 0.48, at least about 0.49, at least about 0.50, at least about 0.51, at least about 0.52, at least about 0.53, at least about 0.54, at least about 0.55, at least about 0.56, at least about 0.57, at least about 0.58, at least about 0.59, at least about 0.60, at least about 0.61, at least about 0.62, at least about 0.63, at least about 0.64, at least about 0.65, at least about 0.66, at least about 0.67, at least about 0.68, at least about 0.69, at least about 0.70, at least about 0.71, at least about 0.72, at least about 0.73, at least about 0.74, at least about 0.75, at least about 0.76, at least about 0.77, at least about 0.78, at least about 0.79, at least about 0.81, at least about 0.82, at least about 0.83, at least about 0.84, at least about 0.85, at least about 0.86, at least about 0.87, at least about 0.88, at least about 0.89, at least about 0.90, at least about 0.91, at least about 0.92, at least about 0.93, at least about 0.94, at least about 0.95, at least about 0.96, at least about 0.97, at least about 0.98, at least about 0.99, or 1.

[0013] In one aspect, provided herein is a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant correlation with the TL1A isoform ratio, wherein optionally the proxy marker relative to a cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenoticdisease or condition. In some embodiments, the proxy marker is identified by the method of described in this paragraph.

[0014] In one aspect, provided herein is a computer-implemented method of determining a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”) for a subject, the method comprising: (a) receiving TL1A expression data obtained from a sample from the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition; (b) analyzing the TL1A expression data with a statistical algorithm configured to produce the TL1A isoform ratio; and (d) applying a cutoff to the TL1A isoform ratio, wherein the TL1A isoform ratio relative to the cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition.

[0015] In another aspect, provided herein is a computer-implemented method of determining a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”) for a subject, the method comprising: (a) obtaining expression data in a sample from the subject; (b) determining expression of TL1A short isoform and TL1A long isoform; (c) calculating the TL1A isoform ratio; and (d) applying a cutoff to the TL1A isoform ratio, wherein the TL1A isoform ratio relative to the cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition.

[0016] In some embodiments of the methods provided herein, based on the TL1A isoform ratio is based on TL1A isoform ratio above a cutoff.

[0017] In some embodiments of the methods provided herein, the TL1A isoform ratio relative to the cutoff is the TL1A isoform ratio above the cutoff.

[0018] In some embodiments of the methods provided herein, the proxy marker comprises rs6478109.

[0019] In some embodiments of the methods provided herein, based on the proxy marker is (i) based on the proxy marker above a cutoff if the proxy marker and the TL1A isoform ratio has a positive correlation (such proxy marker as “positive proxy marker”); or (ii) based on the proxy marker below a cutoff if the proxy marker and the TL1A isoform ratio has a negative correlation (such proxy marker as “inverse proxy marker”).

[0020] In some embodiments of the methods provided herein, the positive proxy marker is identified by a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1Aisoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant positive correlation with the TL1A isoform ratio, wherein optionally the proxy marker relative to a cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition.

[0021] In some embodiments of the methods provided herein, TL1A isoform ratio or a positive proxy marker above a cutoff is determined if an inverse-proxy marker is below an alternative cutoff, wherein the inverse proxy marker has a negative correlation with the TL1A isoform ratio. In some embodiments of the methods provided herein, inverse proxy marker comprises the ratio of TL1A long isoform to the TL1A short isoform (TL1Along / TL1Ashort).

[0022] In some embodiments of the methods provided herein, the inverse proxy marker is identified by a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant negative correlation with the TL1A isoform ratio, wherein optionally the proxy marker relative to a cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition.

[0023] In some embodiments of the methods provided herein, the TL1A isoform ratio above a cutoff is determined if the ratio of TL1A long isoform to the TL1A short isoform is below an alternative cutoff.

[0024] In some embodiments of the methods provided herein, the cutoff ranges from about 0.090 to about 0.110. In some embodiments, the cutoff is about 0.097. In some embodiments, the cutoff in this paragraph is for selecting CD patients.

[0025] In some embodiments of the methods provided herein, the cutoff ranges from about 0.080 to about 0.10. In some embodiments the cutoff is about 0.085. In some embodiments, the cutoff in this paragraph is for selecting UC patients.

[0026] In some embodiments of the methods provided herein, the cutoff is (i) the TL1A isoform ratio or proxy marker level in a heathy subject without the inflammatory, fibrotic, or fibrostenotic disease or condition or (ii) the TL1A isoform ratio or proxy marker level in a tissue not afflicted by the inflammatory, fibrotic, or fibrostenotic disease or condition.

[0027] In some embodiments of the methods provided herein, the TL1A isoform ratio is calculated as, TL1Ashort / TL1Along, ln(TL1Ashort / TL1Along), or ln(TL1Ashort / TL1Along+n), wherein TL1Ashort is an expression level of the TL1A short isoform, TL1Along is an expression level of the TL1A long isoform, and n is a positive number. In some embodiments, n is 1.

[0028] In some embodiments of the methods provided herein, the expression level of the TL1A short isoform is the level of gene expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of gene expression of the TL1A long isoform. In some embodiments of the methods provided herein, the expression level of the TL1A short isoform is the level of protein expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of protein expression of the TL1A long isoform. In some embodiments of the methods provided herein, the expression level of the TL1A short isoform is the level of gene expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of protein expression of the TL1A long isoform. In some embodiments of the methods provided herein, the expression level of the TL1A short isoform is the level of protein expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of gene expression of the TL1A long isoform.

[0029] In some embodiments of the methods provided herein, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least about 29%, 30%, 35%, 40%, 45%, 50%, 51%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor ofTL1A activity or expression with a sensitivity of at least about 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive rate of at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or 75%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

[0030] In some embodiments of the methods provided herein, the cutoff is such that the TL1A isoform ratio or the proxy marker above the cutoff is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least about 29%, 30%, 35%, 40%, 45%, 50%, 51%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the cutoff is such that the TL1A isoform ratio or the proxy marker above the cutoff is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the cutoff is such that the TL1A isoform ratio or the proxy marker above the cutoff is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the cutoff is such that the TL1A isoform ratio or the proxy marker above the cutoff is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least about 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the cutoff is such that the TL1A isoform ratio or the proxy marker above the cutoff is predictive of an increase of one or more IBD enriched cell types with a positive rate of at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or 75%. In some embodiments, the cutoff is such that the TL1A isoform ratio or the proxy marker above the cutoff is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

[0031] In some embodiments of the methods provided herein, the TL1A isoform ratio is TL1A isoform ratio in a diseased tissue afflicted by the inflammatory, fibrotic, or fibrostenotic disease25743 or condition. In some embodiments, the diseased tissue is selected from the group consisting of ileum, colon, rectum, or small intestine.

[0032] In some embodiments of the methods provided herein, the TL1A isoform ratio is TL1A isoform ratio in a cell contributory to the inflammatory, fibrotic, or fibrostenotic disease or condition. In some embodiments, the cell is selected from the group consisting of a Goblet cell, a pericyte, a smooth muscle cell, an enterocyte, a clonocyte, a monocyte-derived dendritic cells (moDC), a resident macrophage, or a colon transit-amplifying (TA) cell.

[0033] In some embodiments of the methods provided herein, the TL1A isoform ratio is TL1A isoform ratio in blood of the subject.

[0034] In one aspect, provided herein is a computer-implemented system comprising at least one processor and instructions executable by the at least one processor to provide an application configured to determine a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”) for a subject by performing operations comprising: (a) receiving expression data of TL1A short isoform and TL1A long isoform obtained from a sample from the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition; (b) applying an algorithm to the expression data to produce the TL1A isoform ratio; and (d) applying a cutoff to the TL1A isoform ratio, wherein the TL1A isoform ratio relative to the cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression.

[0035] In another aspect, provided herein is a computer-implemented system comprising at least one processor and instructions executable by the at least one processor to provide an application configured to determine a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”) for a subject by performing operations comprising: (a) receiving expression data of TL1A short isoform and TL1A long isoform obtained from a sample from the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition; and (b) calculating TL1A isoform ratio by utilizing one or more algorithms, wherein the TL1A isoform ratio relative to the cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression.

[0036] In some embodiments of the computer-implemented system provided herein, the TL1A isoform ratio relative to the cutoff is the TL1A isoform ratio above the cutoff.

[0037] In some embodiments of the computer-implemented system provided herein, the cutoff ranges from about 0.090 to 0.110. In some embodiments of the computer-implemented system25743 provided herein, the cutoff is about 0.097. In some embodiments of the computer-implemented system provided in this paragraph, the cutoff is for selecting CD patients.

[0038] In some embodiments of the computer-implemented system provided herein, the cutoff ranges from about 0.080 to 0.10. In some embodiments of the computer-implemented system provided herein, the cutoff is about 0.085. In some embodiments of the computer-implemented system provided in this paragraph, the cutoff is for selecting UC patients.

[0039] In some embodiments of the computer-implemented system provided herein, the cutoff is (i) the TL1A isoform ratio or proxy marker level in a heathy subject without the inflammatory, fibrotic, or fibrostenotic disease or condition or (ii) the TL1A isoform ratio or proxy marker level in a tissue not afflicted by the inflammatory, fibrotic, or fibrostenotic disease or condition.

[0040] In some embodiments of the computer-implemented system provided herein, the TL1A isoform ratio is calculated as, TL1Ashort / TL1Along, ln(TL1Ashort / TL1Along), or ln(TL1Ashort / TL1Along+n), wherein TL1Ashort is an expression level of the TL1A short isoform, TL1Along is an expression level of the TL1A long isoform, and n is a positive number. In some embodiments of the computer-implemented system provided herein, n is 1.

[0041] In some embodiments of the computer-implemented system provided herein, the expression level of the TL1A short isoform is the level of gene expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of gene expression of the TL1A long isoform. In some embodiments of the computer-implemented system provided herein, the expression level of the TL1A short isoform is the level of protein expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of protein expression of the TL1A long isoform. In some embodiments of the computer-implemented system provided herein, the expression level of the TL1A short isoform is the level of gene expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of protein expression of the TL1A long isoform. In some embodiments of the computer- implemented system provided herein, the expression level of the TL1A short isoform is the level of protein expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of gene expression of the TL1A long isoform.

[0042] In some embodiments of the methods or the systems provided herein, the statistically significant correlation is a correlation with p value less than 0.1, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04.0.03, 0.02, or 0.01.25743

[0043] In some embodiments of the methods or the systems provided herein, the computer- implemented system of any one of claims 48 to 61, wherein the subject has been treated with an advanced IBD therapy prior to the treatment with the inhibitor of TL1A activity or expression. In some embodiments of the methods or the systems provided herein, the subject has not been treated with an advanced IBD therapy prior to the treatment with the inhibitor of TL1A activity or expression. In some embodiments of the methods or the systems provided herein, the advanced IBD therapy comprises one or more selected from the group consisting of a biologic therapeutic agent for IBD, an S1P1 modulator, or a JAK inhibitor. In some embodiments of the methods or the systems provided herein, the biologic therapeutic agent for IBD comprises an anti-71)Į^DQWLERG\^^DQ^DQWL-IL23 antibody, or an anti-LQWHJULQ^Į^ȕ^^DQWLERG\^

[0044] In some embodiments of the methods or the systems provided herein, the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A (anti-TL1A antibody or antigen binding fragment), wherein the anti-TL1A antibody or antigen binding fragment comprises a heavy chain variable region comprising: (a) an HCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 1; (b) an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 2-5; and (c) an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 6-9; and a light chain variable region comprising: (d) an LCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 10; (e) an LCDR2 comprising an amino acid sequence set forth by SEQ ID NO: 11; and (f) an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 12-15.

[0045] In some embodiments of the methods or the systems provided herein, the inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen binding fragment, wherein the anti-TL1A antibody or antigen binding fragment comprises a heavy chain variable domain comprising an amino acid sequence at least about 90% identical to any one of SEQ ID NOS: 101-135, or 310-302, and a light chain variable domain comprising an amino acid sequence at least about 90% identical to any one of SEQ ID NOS: 201-206 or 303. In some embodiments of the methods or the systems provided herein, the heavy chain variable domain comprises an amino acid sequence at least about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 101-135, or 310-302. In some embodiments of the methods or the systems provided herein, the light chain variable domain comprises an amino acid sequence at least about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 201-206 or 303.25743

[0046] In some embodiments of the methods or the systems provided herein, the inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen binding fragment, wherein the anti-TL1A antibody or antigen binding fragment comprises: (a) a heavy chain variable framework region comprising a human IGHV1-46*02 framework or a modified human IGHV1- 46*02 framework; and (b) a light chain variable framework region comprising a human IGKV3- 20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region collectively comprise less than about 14 amino acid modifications from the human IGHV1-46*02 framework and the human IGKV3-20 framework. In some embodiments of the methods or the systems provided herein, the amino acid modification of the less than 14 amino acid modifications comprises: (a) the amino acid modification is at position 47 in the heavy chain variable region, and the amino acid at position 47 is R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V; (b) the amino acid modification is at position 45 in the heavy chain variable region, and the amino acid at position 45 is A, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V; (c) the amino acid modification is at position 55 in the heavy chain variable region, and the amino acid at position 55 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y, or V; (d) the amino acid modification is at position 78 in the heavy chain variable region, and the amino acid at position 78 is A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, or Y; (e) the amino acid modification is at position 80 in the heavy chain variable region, and the amino acid at position 80 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y, or V; (f) the amino acid modification is at position 82 in the heavy chain variable region, and the amino acid at position 82 is A, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V; (g) the amino acid modification is at position 89 in the heavy chain variable region, and the amino acid at position 89 is A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, or Y; or (h) the amino acid modification is at position 91 in the heavy chain variable region, and the amino acid at position 91 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y, or V; or a combination of two or more modifications selected from (a) to (h). In some embodiments of the methods or the systems provided herein, the amino acid modification of the less than 14 amino acid modifications comprises: A47R, R45K, M55I, V78A, M80I, R82T, V89A, M91L in the heavy chain variable region, per Aho or Kabat numbering. In some embodiments of the methods or the systems provided herein, the amino acid modification of the less than 14 amino acid modifications comprises: (a) a modification at amino acid position 54 in the light chain variable region; and / or (b) a modification at amino acid position 55 in the light chain variable region; per25743 Aho or Kabat numbering. In some embodiments of the methods or the systems provided herein, the amino acid modification of the less than 14 amino acid modifications comprises: (a) the amino acid modification is at position 54 of the light chain variable region, and the amino acid at position 54 is A, R, N, D, C, Q, E, G, H, I, K, M, F, P, S, T, W, Y, or V; and / or (b) the amino acid modification is at position 55 of the light chain variable region, and the amino acid at position 55 is A, R, N, D, C, Q, E, G, H, I, K, M, F, P, S, T, W, Y, or V. In some embodiments of the methods or the systems provided herein, the amino acid modification of the less than 14 amino acid modifications comprises L54P and / or L55W in the light chain variable region, per Aho or Kabat numbering.

[0047] In some embodiments of the methods or the systems provided herein, the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A and comprises: a heavy chain variable region comprising SEQ ID NO: 301 X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[HCDR2]RX5 TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR[HCDR3]WGQGTTVTVSS, and a light chain variable region comprising SEQ ID NO: 303 EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11IY[LCDR2]GIPDRFSG SGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V. In some embodiments of the methods or the systems provided herein, the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A and comprises: a heavy chain variable region comprising SEQ ID NO: 302 X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[HCDR2]RX5 TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC[HCDR3]WGQGTTVTVSS, and a light chain variable region comprising SEQ ID NO: 303 EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11IY[LCDR2]GIPDRFSG SGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V. In some embodiments of the methods or the systems provided herein, (a) X1 is Q or E; (b) X2 is R or K (c) X3 is A or R; (d) X4 is M or I; (e) X5 is V or A; (f) X6 is M or I; (g) X7 is R or T; (h) X8 is V or A; (i) X9 is M or L (j) X10 is L or P; (k) X11 is L or W; or (l) X1-X11 are any combination of (a) to (k).25743

[0048] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a heavy chain CDR1 as set forth by SEQ ID NO: 1, a heavy chain CDR2 as set forth by any one of SEQ ID NOS: 2-5, a heavy chain CDR3 as set forth by any one of SEQ ID NOS: 6-9, a light chain CDR1 as set forth by SEQ ID NO: 10, a light chain CDR2 as set forth by SEQ ID NO: 11, and a light chain CDR3 as set forth by any one of SEQ ID NOS: 12-15.

[0049] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a heavy chain framework (FR) 1 as set forth by SEQ ID NO: 304, a heavy chain FR2 as set forth by SEQ ID NO: 305 or SEQ ID NO: 313, a heavy chain FR3 as set forth by any one of SEQ ID NOS: 306, 307, 314, or 315, a heavy chain FR4 as set forth by SEQ ID NO: 308, a light chain FR1 as set forth by SEQ ID NO: 309, a light chain FR2 as set forth by SEQ ID NO: 310, a light chain FR3 as set forth by SEQ ID NO: 311, or a light chain FR4 as set forth by SEQ ID NO: 312, or a combination thereof.

[0050] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a human IgG1 Fc region comprising (a) 297A, 297Q, 297G, or 297D, (b) 279F, 279K, or 279L, (c) 228P, (d) 235A, 235E, 235G, 235Q, 235R, or 235S, (e) 237A, 237E, 237K, 237N, or 237R, (f) 234A, 234V, or 234F, (g) 233P, (h) 328A, (i) 327Q or 327T, (j) 329A, 329G, 329Y, or 329R (k) 331S, (l) 236F or 236R, (m) 238A, 238E, 238G, 238H, 238I, 238V, 238W, or 238Y, (n) 248A, (o) 254D, 254E, 254G, 254H, 254I, 254N, 254P, 254Q, 254T, or 254V, (p) 255N, (q) 256H, 256K, 256R, or 256V, (r) 264S, (s) 265H, 265K, 265S, 265Y, or 265A, (t) 267G, 267H, 267I, or 267K, (u) 268K, (v) 269N or 269Q, (w) 270A, 270G, 270M, or 270N, (x) 271T, (y) 272N, (z) 292E, 292F, 292G, or 292I, (aa) 293S, (bb) 301W, (cc) 304E, (dd) 311E, 311G, or 311S, (ee) 316F, (ff) 328V, (gg) 330R, (hh) 339E or 339L, (ii) 343I or 343V, (jj) 373A, 373G, or 373S, (kk) 376E, 376W, or 376Y, (ll) 380D, (mm) 382D or 382P, (nn) 385P, (oo) 424H, 424M, or 424V, (pp) 434I, (qq) 438G, (rr) 439E, 439H, or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T, or 440V, (tt) E233P, (uu) L235E, (vv) L234A and L235A, (ww) L234A, L235A, and G237A, (xx) L234A, L235A, and P329G, (yy) L234F, L235E, and P331S, (zz) L234A, L235E, and G237A, (aaa), L234A, L235E, G237A, and P331S (bbb) L234A, / ^^^$^^*^^^$^^3^^^6^^+^^^$^^$^^^6^^DQG^3^^^6^^,J*^ı^^^^FFF^^ / ^^^$^^ / ^^^$^^DQG^3^^^$^^ (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) any combination of two or more selected from (a) – (uu), per Kabat numbering.25743

[0051] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a human IgG4 Fc region.

[0052] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a Fc region comprising a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 320-362.

[0053] In some embodiments of the methods or the systems provided herein, the antibody of antigen binding fragment comprises a fragment crystallizable (Fc) region comprising reduced antibody-dependent cell-mediated cytotoxicity (ADCC) function as compared to human IgG1 and / or reduced complement-dependent cytotoxicity (CDC) as compared to human IgG1.

[0054] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a Fc region and wherein the Fc comprises the human IgG1 comprises SEQ ID NO: 320.

[0055] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a Fc region and wherein the ADCC function of the Fc region comprising reduced ADCC is at least about 50% reduced as compared to human IgG1.

[0056] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a Fc region and wherein the CDC function of the Fc region comprising reduced CDC is at least about 50% reduced as compared to human IgG1.

[0057] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a Fc region and wherein the Fc comprises (i) a human IgG4 Fc region or (ii) a human IgG4 Fc region comprising (a) S228P, (b) S228P and L235E, or (c) S228P, F234A, and L235A, per Kabat numbering.

[0058] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a Fc region and wherein the Fc comprises a human IgG2 Fc region; IgG2-IgG4 cross-subclass Fc region; IgG2-IgG3 cross-subclass Fc region; IgG2 comprising H268Q, V309L, A330S, P331S (IgG2m4); or IgG2 comprising V234A, G237A, 3^^^6^^+^^^$^^9^^^ / ^^$^^^6^^3^^^6^^,J*^ı^^

[0059] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a Fc region and wherein the Fc comprises a human IgG1 with a substitution selected from 329A, 329G, 329Y, 331S, 236F, 236R, 238A, 238E, 238G, 238H, 238I, 238V, 238W, 238Y, 248A, 254D, 254E, 254G, 254H, 254I, 254N, 254P, 254Q,25743 254T, 254V, 264S, 265H, 265K, 265S, 265Y, 265A, 267G, 267H, 267I, 267K, 434I, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T, and 440V, per Kabat numbering.

[0060] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a Fc region and wherein the Fc comprises a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 320-362.

[0061] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a Fc region and wherein the Fc comprises any one of SEQ ID NOs: 401-413 or a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 401-413.

[0062] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a heavy chain comprising any one of SEQ ID NOs: 501-513 or a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 501-513.

[0063] In some embodiments of the methods or the systems provided herein, the antibody or antigen binding fragment comprises a light chain comprising any one of SEQ ID NO: 514 or a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ 515.

[0064] In some embodiments of the methods or the systems provided herein, the inflammatory, fibrotic, or fibrostenotic disease or condition comprises inflammatory bowel disease, Crohn’s disease, obstructive Crohn’s disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, or primary sclerosing cholangitis. In some embodiments of the methods or the systems provided herein, the Crohn’s disease is ileal, ileocolonic, or colonic Crohn’s disease.

[0065] In some embodiments of the methods or the systems provided herein, the subject has, or is at risk for developing, a non-response or loss-of-response to a standard therapy comprising glucocorticosteriods, anti-TNF therapy, anti-Į^ȕ^^WKHUDS\^^DQWL-IL12p40 therapy, or a combination thereof.

[0066] In some embodiments of the methods or the systems provided herein, the expression of the TL1A short isoform and the expression level of the TL1A long isoform is determined by ELISA, RNA sequencing, PCR, or mass spectrometry.

[0067] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only25743 illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive. 3. INCORPORATION BY REFERENCE

[0068] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material. 4. BRIEF DESCRIPTION OF THE DRAWINGS

[0069] The novel features of the inventive concepts set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also “Figure” and “FIG.” herein), of which:

[0070] FIG.1 shows a workflow according to an embodiment of the present disclosure for processing a biological sample obtained from a subject to inform the selection of a therapeutic agent to treat a disease or a condition of the subject.

[0071] FIG.2 shows a computer-implemented workflow according to an embodiment of the present disclosure for generating an electronic report to a user, such as a physician, comprising a TNFSF15 profile of a subject based on an analysis of the data on TL1A isoforms and / or proxy markers from the subject.

[0072] FIG.3 shows a computer system that is programmed or otherwise configured to implement methods provided herein.

[0073] FIG.4 shows a computer-implemented workflow according to an embodiment of the present disclosure for producing a TNFSF15 profile.25743

[0074] FIGS.5-7 show chromatograms for analytical size exclusion chromatography of anti- TL1A antibodies. FIG.5 shows chromatograms for analytical size exclusion chromatography of antibodies A193, A194, and A195. FIG.6 shows chromatograms for analytical size exclusion chromatography of antibodies A196, A197, and A198. FIG.7 shows chromatograms for analytical size exclusion chromatography of antibodies A199, A200, and A201.

[0075] FIGS.8-9 depict inhibition of interferon gamma in human blood with anti-TL1A antibodies. FIG.8 depicts inhibition of interferon gamma in human blood with anti-TL1A antibodies A219 and A213. FIG.9 depicts inhibition of interferon gamma in human blood with anti-TL1A antibody A212.

[0076] FIGS.10-12 depicts a PLS model demonstrating effect of pH and protein concentration on viscosity. FIG.10 shows a PLS graph, FIG.11 shows a model of the predicted viscosity versus anti-TL1A antibody concentration in mg / mL, and FIG.12 shows a model of the estimated viscosity versus actual viscosity. Viscosity units are in mPa-s.

[0077] FIG.13 graphically depicts TL1A long isoform and TL1A short isoform on chromosome 9. The TL1A long isoform (also known and referred to as the canonical isoform) can comprise the sequence set forth in SEQ ID NO: 2050. The TL1A short isoform can comprise the sequence set forth in SEQ ID NO: 2052. The third TL1A mRNA isoform encoding SEQ ID NO: 2051 was not observed by the inventors in gastrointestinal tissues in IBD patients, and not depicted in FIG.13.

[0078] FIG.14 shows the software design architecture of the assay interpretation software, according to some embodiments herein.

[0079] FIGS.15A-15K show screenshots of the assay interpretation software application from to illustrate the user experience, according to some embodiments herein. The assay interpretation software application comprises a user interface that comprises a login view (FIG.15A), a files view (FIG.15B), a samples view (FIG.15C), a data analyses view (FIG.15D), a new data analysis view (FIG.15E), system settings view (FIG.15F), a clinical settings view (FIG.15G), a clinical study settings view (FIG.15H), a user management view (FIG.15I), an activities view (FIG.15J), or a my profile view (FIG.15K), or any combination thereof.

[0080] FIGS.16A-16B show exemplary clinical trial studies of the anti-TL1A antibodies disclosed herein. FIG.16A depicts the study schema for induction period for the phase 2 clinical trial for A219 in UC in accordance with some embodiments herein. FIG.16B depicts the study25743 schema for open-label extension period for the phase 2 clinical trial for A219 in UC in accordance with some embodiments herein.

[0081] FIGS.17A-17D show mRNA transcript levels of TL1A isoforms in various gastrointestinal tissues. FIG.17A and FIG.17B show mRNA transcript levels of TL1A long isoform and TL1A short isoform, respectively, in biopsy samples obtained before TL1A inhibitor treatment. FIG.17C and FIG.17D show mRNA transcript levels of TL1A long isoform and TL1A short isoform, respectively, in biopsy samples obtained both before and after TL1A inhibitor treatment. The horizontal lines in FIGS.17B and 17D depicts the approximate detection limit if RNAseq is performed at 50 million reads.

[0082] FIG.18 shows both TL1A short and long isoforms were detected in ileum across the course of treatment and no statistically significant changes were seen in the ratio between TL1A short isoform and TL1A long isoform across the time points during the treatment. The early termination has very few data points (as very few patients had early termination) and thus is not a statistically significant time point.

[0083] FIG.19 shows in samples of an IBD patient cohort treated and collected at University of California San Diego, both TL1A short and long isoforms were detected in ileum and colon tissues and the expression of both TL1A short and long isoforms were higher in ileum.

[0084] FIGS.20A-20E show that TL1A isoform ratio has statistically significant association with the CD patients’ endoscopic response to the anti-TL1A treatment. Samples were filtered to those with greater than 0 transcripts per million for short isoform and greater than 0.2 transcripts per million for long isoform. In FIG.20A, a combination of available baseline (before treatment) and after treatment ileal samples were used to determine TL1A isoform ratio. In FIG.20B, a combination of available baseline-only ileal and colon samples were used to determine TL1A isoform ratio. In FIG.20C, only baseline ileal samples were used to determine TL1A isoform ratio for association studies with CD patients’ endoscopic response to the anti-TL1A treatment. In FIG.20D, only basedline colon samples were used to determine TL1A isoform ratio for association studies with CD patients’ endoscopic response to the anti-TL1A treatment. In FIG. 20E, only basedline rectum samples were used to determine TL1A isoform ratio for association studies with CD patients’ endoscopic response to the anti-TL1A treatment.

[0085] FIG.21 shows both TL1A short and long isoforms were detected in colon across the course of treatment and no statistically significant changes were seen in the ratio between TL1A25743 short isoform and TL1A long isoform across the time points during the treatment with anti-TL1A (A219) in UC patients.

[0086] FIGS.22A-22B show that TL1A isoform ratio has statistically significant association with the UC patients’ positive therapeutic response (e.g. clinical remission and endoscopic improvement) to the anti-TL1A treatment. Samples were filtered based on detectable (at greater than 0 transcript per million) levels of short isoform and detectable (at greater than 0.4 transcripts per million) level of long TL1A isoform. In FIG.22A, TL1A short / long isoform ratio from baseline colon samples of UC patients significantly associated with the clinical remission of the UC patients after anti-TL1A treatment (A219 treatment). In FIG.22B, UC patients who had endoscopic improvement after anti-TL1A treatment (A219 treatment) had higher TL1A short / long isoform ratio as determined in baseline colon samples of the UC patients.

[0087] FIGS.23A-23C show the risk alleles for rs6478109 SNP correlated with TL1A short / long isoform ratio in the cohort of CD patients with statistical significance (p<0.05). Samples were filtered based on detectable (at greater than 0.1 transcript per million) levels of short and long TL1A isoforms. FIG.23A shows the transcripts of canonical isoform (long isoform) plotted against the risk alleles of rs6478109, FIG.23B shows the transcripts of the TL1A short isoform plotted against the risk alleles of rs6478109, and FIG.23C shows the TL1A short / long isoform ratio plotted against the risk alleles of rs6478109. In FIGS.23A-23C, 0 indicates homozygous for risk allele (minor allele), 1 indicates heterozygous for risk allele (minor allele) and non-risk (major allele), and 2 indicates homozygous for non-risk allele (major allele).

[0088] FIGS.24A-24B show the validation of TL1A isoform ratio as CDx for selecting CD or UC patients that have a positive therapeutic response to treatment with anti-TL1A antibody (A219). FIG.24A shows the plot of standardized Wilcoxon statistic with TL1A isoform ratio and endoscopic response in CD patients treated with anti-TL1A antibodies (A219). FIG.24B shows the plot of standardized Wilcoxon statistic with TL1A isoform ratio and clinical remission in UC patients treated with anti-TL1A antibodies (A219). In both FIGS.24A (CD patient clinical result) and 24B (UC patient clinical result), a range of cutoffs for using TL1A isoform ratio as a CDx, a specific cutoff for using TL1A isoform ratio as a CDx, and the performance matrix of CDx with such specific TL1A isoform ratio are indicated.25743 5. DETAILED DESCRIPTION

[0089] Provided herein are methods, systems, and kits for treating a subject who may be suitable for treatment with an inhibitor of Tumor Necrosis Factor (Ligand) Superfamily, Member 15 (TL1A) activity or expression, provided the subject is selected based on the TL1A short isoform to TL1A long isoform ratio (TL1A isoform ratio or TL1A short / long isoform ratio) or a proxy marker thereto. The subject may be a patient, who may be diagnosed with an inflammatory disease, a fibrostenotic disease, or a fibrotic disease, such as inflammatory bowel disease (IBD) or Crohn’s disease (CD). The subject may not be a patient, but may be suspected of having the inflammatory disease, the fibrostenotic disease, or the fibrotic disease. The TL1A isoform ratio may, in some cases, be useful for treating the inflammatory fibrostenotic, or fibrotic disease or condition, as mediated by TL1A. The subject, in some embodiments, is treated by administering the inhibitor of TL1A activity or expression (e.g., anti-TL1A antibody) to the subject, provided the TL1A isoform ratio or the proxy marker is detected. In some cases, identifying the subject as being suitable for treatment with the inhibitor of activity or expression is required in order to administer the inhibitor to the subject.

[0090] The TL1A isoform ratio described herein are detected using suitable assays and devices (e.g., array, sequencing). In some instances, a sample is obtained from the subject or patient indirectly or directly. In some instances, the sample may be obtained by the subject. In other instances, the sample may be obtained by a healthcare professional, such as a nurse or physician. The sample may be derived from biological fluid or tissue containing gene expression information or genetic information, such as blood or tissue biopsy.

[0091] The subject disclosed herein can be a mammal, such as for example a mouse, rat, guinea pig, rabbit, non-human primate, or farm animal. In some instances, the subject is human. In some instances, the subject is suffering from a symptom related to a disease or condition disclosed herein (e.g., abdominal pain, cramping, diarrhea, rectal bleeding, fever, weight loss, fatigue, loss of appetite, dehydration, and malnutrition, anemia, or ulcers).

[0092] In some embodiments, the subject is susceptible to, or is inflicted with, thiopurine toxicity, or a disease caused by thiopurine toxicity (such as pancreatitis or leukopenia). The subject may experience, or is suspected of experiencing, non-response or loss-of-response to a standard treatment (e.g., anti-TNF alpha therapy, anti-a4-b7 therapy (vedolizumab), anti-IL12p40 therapy (ustekinumab), Thalidomide, or Cytoxin).25743

[0093] The disease or condition disclosed herein may be an inflammatory disease, a fibrostenotic disease, or a fibrotic disease. In some instances, the disease or the condition is a TL1A-mediated disease or condition. The term, “TL1A-mediated disease or condition” refers to a disease or a condition pathology or pathogenesis that is driven, at least in part, by TL1A signaling. In some instances, the disease or the condition is immune-mediated disease or condition, such as those mediated by TL1A.

[0094] In some embodiments the disease or the condition is an inflammatory disease or disorder that is mediated, at least in part, by TL1A signaling. Non-limiting examples of inflammatory disease include, allergy, ankylosing spondylitis, asthma, atopic dermatitis, autoimmune diseases or disorders, cancer, celiac disease, chronic obstructive pulmonary disease (COPD), chronic peptic ulcer, cystic fibrosis, diabetes (e.g., type 1 diabetes and type 2 diabetes), glomerulonephritis, gout, hepatitis (e.g., active hepatitis), an immune-mediated disease or disorder, inflammatory bowel disease (IBD) such as Crohn’s disease and ulcerative colitis, myositis, osteoarthritis, pelvic inflammatory disease (PID), multiple sclerosis, neurodegenerative diseases of aging, periodontal disease (e.g., periodontitis), preperfusion injury transplant rejection, psoriasis, pulmonary fibrosis, rheumatic disease, scleroderma, sinusitis, tuberculosis.

[0095] In some embodiments, the disease or the condition is an autoimmune disease that is mediated, at least in part, by TL1A signaling. Non-limiting examples of autoimmune disease or disorder include Achalasia, Addison’s disease, Adult Still's disease, Agammaglobulinemia, Alopecia areata, Amyloidosis, Ankylosing spondylitis, Anti-GBM / Anti-TBM nephritis, Antiphospholipid syndrome, Autoimmune angioedema, Autoimmune dysautonomia, Autoimmune encephalomyelitis, Autoimmune hepatitis, Autoimmune inner ear disease (AIED), Autoimmune myocarditis, Autoimmune oophoritis, Autoimmune orchitis, Autoimmune pancreatitis, Autoimmune retinopathy, Autoimmune urticaria, Axonal & neuronal neuropathy (AMAN), Baló disease, Behcet’s disease, Benign mucosal pemphigoid, Bullous pemphigoid, Castleman disease (CD), Celiac disease, Chagas disease, Chronic inflammatory demyelinating polyneuropathy (CIDP), Chronic recurrent multifocal osteomyelitis (CRMO), Churg-Strauss Syndrome (CSS) or Eosinophilic Granulomatosis (EGPA), Cicatricial pemphigoid, Cogan’s syndrome, Cold agglutinin disease, Congenital heart block, Coxsackie myocarditis, CREST syndrome, Crohn’s disease, Dermatitis herpetiformis, Dermatomyositis, Devic’s disease (neuromyelitis optica), Discoid lupus, Dressler’s syndrome, Endometriosis, Eosinophilic esophagitis (EoE), Eosinophilic fasciitis, Erythema nodosum, Essential mixed cryoglobulinemia,25743 Evans syndrome, Fibromyalgia, Fibrosing alveolitis, Giant cell arteritis (temporal arteritis), Giant cell myocarditis, Glomerulonephritis, Goodpasture’s syndrome, Granulomatosis with Polyangiitis, Graves’ disease, Guillain-Barre syndrome, Hashimoto’s thyroiditis, Hemolytic anemia, Henoch-Schonlein purpura (HSP), Herpes gestationis or pemphigoid gestationis (PG), Hidradenitis Suppurativa (HS) (Acne Inversa), Hypogammalglobulinemia, IgA Nephropathy, IgG4-related sclerosing disease, Immune thrombocytopenic purpura (ITP), Inclusion body myositis (IBM), Interstitial cystitis (IC), Juvenile arthritis, Juvenile diabetes (Type 1 diabetes), Juvenile myositis (JM), Kawasaki disease, Lambert-Eaton syndrome, Leukocytoclastic vasculitis, Lichen planus, Lichen sclerosus, Ligneous conjunctivitis, Linear IgA disease (LAD), Lupus, Lyme disease chronic, Meniere’s disease, Microscopic polyangiitis (MPA), Mixed connective tissue disease (MCTD), Mooren’s ulcer, Mucha-Habermann disease, Multifocal Motor Neuropathy (MMN) or MMNCB, Multiple sclerosis, Myasthenia gravis, Myositis, Narcolepsy, Neonatal Lupus, Neuromyelitis optica, Neutropenia, Ocular cicatricial pemphigoid, Optic neuritis, Palindromic rheumatism (PR), PANDAS, Paraneoplastic cerebellar degeneration (PCD), Paroxysmal nocturnal hemoglobinuria (PNH), Parry Romberg syndrome, Pars planitis (peripheral uveitis), Parsonage-Turner syndrome, Pemphigus, Peripheral neuropathy, Perivenous encephalomyelitis, Pernicious anemia (PA), POEMS syndrome, Polyarteritis nodosa, Polyglandular syndromes type I, II, III, Polymyalgia rheumatica, Polymyositis, Postmyocardial infarction syndrome, Postpericardiotomy syndrome, Primary biliary cirrhosis, Primary sclerosing cholangitis, Progesterone dermatitis, Psoriasis, Psoriatic arthritis, Pure red cell aplasia (PRCA), Pyoderma gangrenosum, Raynaud’s phenomenon, Reactive Arthritis, Reflex sympathetic dystrophy, Relapsing polychondritis, Restless legs syndrome (RLS), Retroperitoneal fibrosis, Rheumatic fever, Rheumatoid arthritis, Sarcoidosis, Schmidt syndrome, Scleritis, Scleroderma, Sjögren’s syndrome, Sperm & testicular autoimmunity, Stiff person syndrome (SPS), Subacute bacterial endocarditis (SBE), Susac’s syndrome, Sympathetic ophthalmia (SO), Takayasu’s arteritis, Temporal arteritis / Giant cell arteritis, Thrombocytopenic purpura (TTP), Tolosa-Hunt syndrome (THS), Transverse myelitis, Type 1 diabetes, Ulcerative colitis (UC), Undifferentiated connective tissue disease (UCTD), Uveitis, Vasculitis, Vitiligo, and Vogt-Koyanagi-Harada Disease.

[0096] In some embodiments, the disease or the condition is a cancer that is mediated, at least in part, by TL1A signaling. Non-limiting examples of cancers include Adenoid Cystic Carcinoma, Adrenal Gland Cancer, Amyloidosis, Anal Cancer, Ataxia-Telangiectasia, Atypical25743 Mole Syndrome, Basal Cell Carcinoma, Bile Duct Cancer, Birt Hogg Dube Syndrome, Bladder Cancer, Bone Cancer, Brain Tumor, Breast Cancer, Breast Cancer in Men, Carcinoid Tumor, Cervical Cancer, Colorectal Cancer, Ductal Carcinoma, Endometrial Cancer, Esophageal Cancer, Gastric Cancer, Gastrointestinal Stromal Tumor (GIST), HER2-Positive Breast Cancer, Islet Cell Tumor, Juvenile Polyposis Syndrome, Kidney Cancer, Laryngeal Cancer, Leukemia - Acute Lymphoblastic Leukemia, Leukemia - Acute Lymphocytic (ALL), Leukemia - Acute Myeloid AML, Leukemia - Adult, Leukemia - Childhood, Leukemia - Chronic Lymphocytic (CLL), Leukemia - Chronic Myeloid (CML), Liver Cancer, Lobular Carcinoma, Lung Cancer, Lung Cancer - Small Cell (SCLC), Lung Cancer - Non-small Cell (NSCLC), Lymphoma - Hodgkin's, Lymphoma - Non-Hodgkin's, Malignant Glioma, Melanoma, Meningioma, Multiple Myeloma, Myelodysplastic Syndrome (MDS), Nasopharyngeal Cancer, Neuroendocrine Tumor, Oral Cancer, Osteosarcoma, Ovarian Cancer, Pancreatic Cancer, Pancreatic Neuroendocrine Tumors, Parathyroid Cancer, Penile Cancer, Peritoneal Cancer, Peutz-Jeghers Syndrome, Pituitary Gland Tumor, Polycythemia Vera, Prostate Cancer, Renal Cell Carcinoma, Retinoblastoma, Salivary Gland Cancer, Sarcoma, Sarcoma - Kaposi, Skin Cancer, Small Intestine Cancer, Stomach Cancer, Testicular Cancer, Thymoma, Thyroid Cancer, Uterine (Endometrial) Cancer, Vaginal Cancer, and Wilms’ Tumor.

[0097] In some embodiments, the disease or the condition is an inflammatory bowel disease, such as Crohn’s disease (CD) or ulcerative colitis (UC). A subject may suffer from fibrosis, fibrostenosis, or a fibrotic disease, either isolated or in combination with an inflammatory disease. In some cases, the CD is severe CD. The severe CD may result from inflammation that has led to the formation of scar tissue in the intestinal wall (fibrostenosis) and / or swelling. In some cases, the severe CD is characterized by the presence of fibrotic and / or inflammatory strictures. The strictures may be determined by computed tomography enterography (CTE), and magnetic resonance imaging enterography (MRE). The disease or condition may be characterized as refractory, which in some cases, means the disease is resistant to a standard treatment (e.g., anti-71)Į^^WKHUDS\^^^1RQ-limiting examples of standard treatment include glucocorticosteriods, anti-TNF therapy, anti-a4-b7 therapy (vedolizumab), anti-IL12p40 therapy (ustekinumab), Thalidomide, and Cytoxin.

[0098] Disclosed herein are TL1A isoforms, TL1A isoform ratios, and a proxy maker thereto that may be detected in a sample obtained from a subject by analyzing the nucleic acid and protein material in the sample. In some instances, the subject may be human. In someembodiments, the genetic material is obtained from a subject having a disease or condition disclosed herein. In some cases, the nucleic acid and protein material is obtained from blood, serum, plasma, and / or tissue biopsies by techniques known by one of skill in the art. In some cases, the nucleic acid and protein material is obtained from a biopsy, e.g., from the intestinal track of the subject.

[0099] Aspects disclosed herein provide TL1A isoform ratio or a proxy marker thereto that is associated with, and therefore indicative of, a subject associated with an increase TNFSF15 (TL1A) expression or activity contributory to an inflammatory, a fibrotic, or a fibrostenotic disease or condition in the subject (such as CD and UC). Thus, the TL1A isoform ratio or a proxy marker thereto is indicative that the subject will have a positive therapeutic response to an inhibitor of TL1A activity or expression. The term, “positive therapeutic response” refers to a reduction or an elimination of at least one symptom of the disease or the condition (e.g., Cohn’s disease) after induction of a therapy (e.g., anti-TL1A antibody).

[0100] The TL1A isoform ration or the proxy marker thereof has already been validated to correlate with an increase of a positive therapeutic response in IBD patients to a treatment with the inhibitor of TL1A activity or expression, as further described in Section 7 (EXAMPLES). As such, the disclosure provides that the TL1A isoform ratio or the proxy marker thereof provided herein can be used as criteria for identifying subjects or patients for the various methods provided herein including in Sections 2, 5.1, and 7 (EXAMPLES). Similarly, the disclosure provides that the TL1A isoform ratio or the proxy marker thereof provided herein can be used as criteria for identifying subjects or patients for the various kits and compositions provided herein including in Sections 2, 5.4, 5.5, and 7 (EXAMPLES). Additionally, the disclosure provides that the TL1A isoform ratio or the proxy marker thereof provided herein can be used as criteria for the various methods of selecting patients provided herein including in Sections 2, 5.1, and 7.

[0101] The disclosure further provides simple methods to validate the suitability of the TL1A isoform ratio or the proxy marker thereof for the various methods of treatment, methods of selecting patients, and / or the kits and compositions provided herein including in Sections 2, 5.1, 5.4, 5.5, and 7.

[0102] The TL1A isoform ratio or the proxy marker thereof provided in the Examples may be used to predict a positive therapeutic response in a subject or a patient to an inhibitor of TL1A activity or expression (e.g., anti-TL1A antibody), either alone, or in combinations. The TL1A isoform ratio or the proxy marker thereof described herein may be used in a diagnostic orprognostic test to identify a subject suitable for treatment with an inhibitor of TL1A activity or expression to treat a disease or condition described herein in the subject. In some cases, the diagnostic is a companion diagnostic test, such as for example, a TL1A companion diagnostic test (“TL1A CDx”).

[0103] To validate the CDx based on the TL1A isoform ratio or the proxy marker thereof, an external cohort of IBD (e.g., UC or CD) patients can be identified and their biopsied tissue samples assayed to determine the TL1A isoform ratio or the proxy marker thereof. The positive predictive value, negative predictive value, specificity, sensitivity, and positive rate of the patient population can be calculated from the patients that have the TL1A isoform ratio or the proxy marker and the clinical response or clinical remission of the IBD patients after the TL1A inhibitor therapy, for example as described in Section 7 (Examples). The cutoff value for the TL1A isoform ratio used to make CDx positive or CDx negative determination for a given positive predictive value, negative predictive value, specificity, sensitivity, and / or positive rate can be identified by the machine learning algorithms and validated as provided herein without undue experimentation.

[0104] In some embodiments, the elevated TL1A expression and elevated TL1A activity in this Section (including in the preceding paragraphs) are in reference to such in a tissue or subject not affected by IBD (e.g. UC or CD). 5.1 Methods of Treatment

[0105] Disclosed herein are methods of treating a disease or condition, or a symptom of the disease or condition, in a subject, comprising administrating of therapeutic effective amount of one or more therapeutic agents to the subject. In some embodiments, the one or more therapeutic agents is administered to the subject alone (e.g., standalone therapy). In some embodiments, the one or more therapeutic agents is administered in combination with an additional agent. In some embodiments, the therapeutic agent is a first-line therapy for the disease or condition. In some embodiments, the therapeutic agent is a second-line, third-line, or fourth-line therapy, for the disease or condition. In some embodiments, the therapeutic agent comprises an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression.

[0106] Various embodiments provide for methods of treating inflammatory bowel disease (IBD), comprising administering an anti-TL1A antibody described herein to a subject in need thereof. In some embodiments, the subject comprises the TL1A isoform ratio or the proxy marker. In some embodiments, the IBD is a severe form of IBD.25743

[0107] In one aspect, provided herein is method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, wherein the subject is selected based on a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof.

[0108] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) subjecting the sample to an assay adapted to determine a TL1A isoform ratio, a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof; (iii) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the TL1A isoform ratio or the proxy marker; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0109] In a further aspect, provided herein is a method of determining a TL1A isoform ratio or a proxy marker having a statistically significant correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; and (c) determining a ratio TL1A isoform ratio, a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the TL1A isoform ratio or the proxy marker.

[0110] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising:25743 (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; (c) determining a TL1A isoform ratio, a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof; and (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the TL1A isoform ratio or the proxy marker.

[0111] In one aspect, provided herein is method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, wherein the subject is selected based on a TL1A isoform ratio.

[0112] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) subjecting the sample to an assay adapted to determine a TL1A isoform ratio; (iii) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the TL1A isoform ratio; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0113] In a further aspect, provided herein is a method of determining a TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; and (c) determining a ratio TL1A isoform ratio, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the TL1A isoform ratio.25743

[0114] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; (c) determining a TL1A isoform ratio; and (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the TL1A isoform ratio.

[0115] In one aspect, provided herein is method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, wherein the subject is selected based on a proxy marker having a statistically significant correlation with the TL1A isoform ratio.

[0116] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) subjecting the sample to an assay adapted to determine a proxy marker having a statistically significant correlation with the TL1A isoform ratio; (iii) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the proxy marker; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0117] In a further aspect, provided herein is a method of determining a proxy marker having a statistically significant correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect the proxy marker; and (c) determining the proxy marker, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the proxy marker.25743

[0118] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect a proxy marker having a statistically significant correlation with the TL1A isoform ratio; (c) determining the proxy marker; and (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the proxy marker.

[0119] In one aspect, provided herein is method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, wherein the subject is selected based on a proxy marker having a statistically significant correlation with the TL1A isoform ratio, wherein the correlation is positive correlation.

[0120] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) subjecting the sample to an assay adapted to determine a proxy marker having a statistically significant correlation with the TL1A isoform ratio, wherein the correlation is positive correlation; (iii) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the proxy marker; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0121] In a further aspect, provided herein is a method of determining a proxy marker having a statistically significant correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject;25743 (b) subjecting the sample to an assay adapted to detect the proxy marker; and (c) determining the proxy marker, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the proxy marker, wherein the correlation is positive correlation.

[0122] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect a proxy marker having a statistically significant correlation with the TL1A isoform ratio, wherein the correlation is positive correlation; (c) determining the proxy marker; and (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the proxy marker.

[0123] In various method provided herein, including in the preceding paragraphs of this Section, the method further comprises preparing nucleic acids from the sample.

[0124] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) preparing nucleic acids from the sample; (iii) subjecting the sample to an assay adapted to determine a TL1A isoform ratio, a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof; (iv) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the TL1A isoform ratio or the proxy marker; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0125] In a further aspect, provided herein is a method of determining a TL1A isoform ratio or a proxy marker having a statistically significant correlation with the TL1A isoform ratio for a25743 subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; and (d) determining a ratio TL1A isoform ratio, a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the TL1A isoform ratio or the proxy marker.

[0126] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; (d) determining a TL1A isoform ratio, a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof; and (e) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the TL1A isoform ratio or the proxy marker.

[0127] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) preparing nucleic acids from the sample; (iii) subjecting the sample to an assay adapted to determine a TL1A isoform ratio; (iv) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the TL1A isoform ratio; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.25743

[0128] In a further aspect, provided herein is a method of determining a TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; and (d) determining a ratio TL1A isoform ratio, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the TL1A isoform ratio.

[0129] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; (d) determining a TL1A isoform ratio; and (e) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the TL1A isoform ratio.

[0130] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) preparing nucleic acids from the sample; (iii) subjecting the sample to an assay adapted to determine a proxy marker having a statistically significant correlation with the TL1A isoform ratio; (iv) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the proxy marker; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.25743

[0131] In a further aspect, provided herein is a method of determining a proxy marker having a statistically significant correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect the proxy marker; and (d) determining the proxy marker, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the proxy marker.

[0132] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect a proxy marker having a statistically significant correlation with the TL1A isoform ratio; (d) determining the proxy marker; and (e) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the proxy marker.

[0133] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) preparing nucleic acids from the sample; (iii) subjecting the sample to an assay adapted to determine a proxy marker having a statistically significant correlation with the TL1A isoform ratio, wherein the correlation is positive correlation; (iv) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the proxy marker; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.25743

[0134] In a further aspect, provided herein is a method of determining a proxy marker having a statistically significant correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect the proxy marker; and (d) determining the proxy marker, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the proxy marker, wherein the correlation is positive correlation.

[0135] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect a proxy marker having a statistically significant correlation with the TL1A isoform ratio, wherein the correlation is positive correlation; (d) determining the proxy marker; and (e) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the proxy marker.

[0136] In one aspect, provided herein is method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, wherein the subject is selected based on a TL1A isoform ratio above a cutoff, a proxy marker above a cutoff, or a combination thereof, wherein the proxy marker has a statistically significant positive correlation with the TL1A isoform ratio.

[0137] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) subjecting the sample to an assay adapted to determine a TL1A isoform ratio,25743 a proxy marker having a statistically significant positive correlation with the TL1A isoform ratio, or a combination thereof; (iii) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the TL1A isoform ratio above a cutoff or the proxy marker above a cutoff; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0138] In a further aspect, provided herein is a method of determining a TL1A isoform ratio or a proxy marker having a statistically significant positive correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; and (c) determining the ratio TL1A isoform ratio, the proxy marker, or a combination thereof, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the TL1A isoform ratio above a cutoff or the proxy marker above a cutoff.

[0139] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; (c) determining a TL1A isoform ratio, a proxy marker having a statistically significant positive correlation with the TL1A isoform ratio, or a combination thereof; and (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the TL1A isoform ratio above a cutoff or the proxy marker above a cutoff.

[0140] In one aspect, provided herein is method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine25743 1A (TL1A) activity or expression, wherein the subject is selected based on a TL1A isoform ratio above a cutoff.

[0141] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) subjecting the sample to an assay adapted to determine a TL1A isoform ratio; (iii) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the TL1A isoform ratio above a cutoff; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0142] In a further aspect, provided herein is a method of determining a TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; and (c) determining a ratio TL1A isoform ratio, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the TL1A isoform ratio above a cutoff.

[0143] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; (c) determining a TL1A isoform ratio; and (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the TL1A isoform ratio above a cutoff.

[0144] In one aspect, provided herein is method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: administering to the25743 subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, wherein the subject is selected based on a proxy marker above a cutoff, wherein the proxy marker has a statistically significant positive correlation with the TL1A isoform ratio.

[0145] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) subjecting the sample to an assay adapted to determine a proxy marker having a statistically significant correlation with the TL1A isoform ratio, wherein the correlation is positive correlation; (iii) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the proxy marker above a cutoff; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0146] In a further aspect, provided herein is a method of determining a proxy marker having a statistically significant correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect the proxy marker; and (c) determining the proxy marker, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the proxy marker above a cutoff, wherein the correlation is positive correlation.

[0147] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect a proxy marker having a statistically significant correlation with the TL1A isoform ratio, wherein the correlation is positive correlation;25743 (c) determining the proxy marker; and (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the proxy marker above a cutoff.

[0148] In various method provided herein, including in the preceding paragraphs of this Section, the method further comprises preparing nucleic acids from the sample.

[0149] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) preparing nucleic acids from the sample; (iii) subjecting the sample to an assay adapted to determine a TL1A isoform ratio, a proxy marker having a statistically significant positive correlation with the TL1A isoform ratio, or a combination thereof; (iv) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the TL1A isoform ratio above a cutoff, the proxy marker above a cutoff or a combination thereof; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0150] In a further aspect, provided herein is a method of determining a TL1A isoform ratio or a proxy marker having a statistically significant positive correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; and (d) determining the ratio TL1A isoform ratio, the proxy marker, or a combination thereof, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the TL1A isoform ratio above a cutoff, the proxy marker above a cutoff or a combination thereof.25743

[0151] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; (d) determining a TL1A isoform ratio, a proxy marker having a statistically significant positive correlation with the TL1A isoform ratio, or a combination thereof; and (e) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the TL1A isoform ratio above a cutoff, the proxy marker above a cutoff, or a combination thereof.

[0152] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) preparing nucleic acids from the sample; (iii) subjecting the sample to an assay adapted to determine a TL1A isoform ratio; (iv) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the TL1A isoform ratio above a cutoff; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0153] In a further aspect, provided herein is a method of determining a TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; and (d) determining a ratio TL1A isoform ratio, wherein whether the subject is suitable for25743 treatment with an inhibitor of TL1A activity or expression is indicated based on the TL1A isoform ratio above a cutoff.

[0154] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; (d) determining a TL1A isoform ratio; and (e) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the TL1A isoform ratio above a cutoff.

[0155] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) preparing nucleic acids from the sample; (iii) subjecting the sample to an assay adapted to determine a proxy marker having a statistically significant positive correlation with the TL1A isoform ratio; (iv) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the proxy marker above a cutoff; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0156] In a further aspect, provided herein is a method of determining a proxy marker having a statistically positive significant correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect the proxy marker; and (d) determining the proxy marker, wherein whether the subject is suitable for treatment25743 with an inhibitor of TL1A activity or expression is indicated based on the proxy marker above a cutoff.

[0157] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect a proxy marker having a statistically significant positive correlation with the TL1A isoform ratio; (d) determining the proxy marker; and (e) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the proxy marker above a cutoff.

[0158] In one aspect, provided herein is method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, wherein the subject is selected based on a TL1A isoform ratio above a cutoff, a proxy marker below a cutoff, or a combination thereof, wherein the proxy marker has a statistically significant negative correlation with the TL1A isoform ratio.

[0159] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) subjecting the sample to an assay adapted to determine a TL1A isoform ratio, a proxy marker having a statistically significant negative correlation with the TL1A isoform ratio, or a combination thereof; (iii) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the TL1A isoform ratio above a cutoff, the proxy marker below a cutoff, or a combination thereof; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0160] In a further aspect, provided herein is a method of determining a TL1A isoform ratio or a proxy marker having a statistically significant negative correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; and (c) determining the ratio TL1A isoform ratio, the proxy marker, or a combination thereof, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the TL1A isoform ratio above a cutoff, the proxy marker below a cutoff, or a combination thereof.

[0161] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; (c) determining a TL1A isoform ratio, a proxy marker having a statistically significant negative correlation with the TL1A isoform ratio, or a combination thereof; and (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the TL1A isoform ratio above a cutoff, the proxy marker below a cutoff, or a combination thereof.

[0162] In one aspect, provided herein is method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, wherein the subject is selected based on a proxy marker below a cutoff, wherein the proxy marker has a statistically significant negative correlation with the TL1A isoform ratio.

[0163] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by:(i) obtaining or having obtained a sample from the subject; (ii) subjecting the sample to an assay adapted to determine a proxy marker having a statistically significant correlation with the TL1A isoform ratio, wherein the correlation is negative correlation; (iii) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the proxy marker below a cutoff; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0164] In a further aspect, provided herein is a method of determining a proxy marker having a statistically significant negative correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect the proxy marker; and (c) determining the proxy marker, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the proxy marker below a cutoff, wherein the correlation is negative correlation.

[0165] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect a proxy marker having a statistically significant correlation with the TL1A isoform ratio, wherein the correlation is negative correlation; (c) determining the proxy marker; and (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the proxy marker below a cutoff.

[0166] In various method provided herein, including in the preceding paragraphs of this Section, the method further comprises preparing nucleic acids from the sample.

[0167] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising:25743 (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) preparing nucleic acids from the sample; (iii) subjecting the sample to an assay adapted to determine a TL1A isoform ratio, a proxy marker having a statistically significant negative correlation with the TL1A isoform ratio, or a combination thereof; (iv) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the TL1A isoform ratio above a cutoff, the proxy marker below a cutoff or a combination thereof; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0168] In a further aspect, provided herein is a method of determining a TL1A isoform ratio or a proxy marker having a statistically significant negative correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; and (d) determining the ratio TL1A isoform ratio, the proxy marker, or a combination thereof, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the TL1A isoform ratio above a cutoff, the proxy marker below a cutoff or a combination thereof.

[0169] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; (d) determining a TL1A isoform ratio, a proxy marker having a statistically significant25743 negative correlation with the TL1A isoform ratio, or a combination thereof; and (e) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the TL1A isoform ratio above a cutoff, the proxy marker below a cutoff, or a combination thereof.

[0170] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) preparing nucleic acids from the sample; (iii) subjecting the sample to an assay adapted to determine a proxy marker having a statistically significant negative correlation with the TL1A isoform ratio; (iv) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the proxy marker below a cutoff; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0171] In a further aspect, provided herein is a method of determining a proxy marker having a statistically negative significant correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect the proxy marker; and (d) determining the proxy marker, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the proxy marker below a cutoff.

[0172] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect a proxy marker having a statistically significant negative correlation with the TL1A isoform ratio;25743 (d) determining the proxy marker; and (e) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the proxy marker below a cutoff.

[0173] In one aspect, provided herein is method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, wherein the subject is selected based on a proxy marker having a statistically significant negative correlation with the TL1A isoform ratio according to (i) or (ii): (i) the subject is selected based on the proxy marker above a cutoff if the proxy marker and the TL1A isoform ratio has a positive correlation (such proxy marker as “positive proxy marker”); or (ii) the subject is selected based on the proxy marker below a cutoff if the proxy marker and the TL1A isoform ratio has a negative correlation (such proxy marker as “inverse proxy marker”).

[0174] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) subjecting the sample to an assay adapted to determine a proxy marker having a statistically significant correlation with the TL1A isoform ratio; (iii) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the proxy marker according to (1) the subject is suitable based on the proxy marker above a cutoff if the proxy marker and the TL1A isoform ratio has a positive correlation; or (2) the subject is suitable based on the proxy marker below a cutoff if the proxy marker and the TL1A isoform ratio has a negative correlation; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0175] In a further aspect, provided herein is a method of determining a proxy marker having a statistically significant correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising:25743 (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect the proxy marker; and (c) determining the proxy marker, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the proxy marker according to (i) the subject is suitable based on the proxy marker above a cutoff if the proxy marker and the TL1A isoform ratio has a positive correlation; or (ii) the subject is suitable based on the proxy marker below a cutoff if the proxy marker and the TL1A isoform ratio has a negative correlation.

[0176] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect a proxy marker having a statistically significant correlation with the TL1A isoform ratio; (c) determining the proxy marker; and (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the proxy marker according to (i) the subject is selected based on the proxy marker above a cutoff if the proxy marker and the TL1A isoform ratio has a positive correlation; or (ii) the subject is selected based on the proxy marker below a cutoff if the proxy marker and the TL1A isoform ratio has a negative correlation.

[0177] In various method provided herein, including in the preceding paragraphs of this Section, the method further comprises preparing nucleic acids from the sample.

[0178] In another aspect, provided herein is a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) preparing nucleic acids from the sample; (iii) subjecting the sample to an assay adapted to determine a proxy marker having a statistically significant correlation with the TL1A isoform ratio; (iv) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the proxy marker according to (1) the subject is suitable based on25743 the proxy marker above a cutoff if the proxy marker and the TL1A isoform ratio has a positive correlation; or (2) the subject is suitable based on the proxy marker below a cutoff if the proxy marker and the TL1A isoform ratio has a negative correlation; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0179] In a further aspect, provided herein is a method of determining a proxy marker having a statistically significant correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect the proxy marker; and (d) determining the proxy marker, wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the proxy marker according to (i) the subject is suitable based on the proxy marker above a cutoff if the proxy marker and the TL1A isoform ratio has a positive correlation; or (ii) the subject is suitable based on the proxy marker below a cutoff if the proxy marker and the TL1A isoform ratio has a negative correlation.

[0180] In yet another aspect, provided herein is a method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) preparing nucleic acids from the sample; (c) subjecting the sample to an assay adapted to detect a proxy marker having a statistically significant correlation with the TL1A isoform ratio; (d) determining the proxy marker; and (e) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the proxy marker according to (i) the subject is suitable based on the proxy marker above a cutoff if the proxy marker and the TL1A isoform ratio has a positive correlation; or (ii) the subject is suitable based on the proxy marker below a cutoff if the proxy marker and the TL1A isoform ratio has a negative correlation.

[0181] As is clear from the descriptions herein, the proxy marker can have a positive correlation with the TL1A isoform ratio. When the proxy marker has a positive correlation with25743 the TL1A isoform, the proxy marker moves in the same direction as the TL1A isoform ratio with regard to increased probability of positive therapeutic response to an anti-TL1A treatment in IBD patients. Specifically, when the proxy marker has a positive correlation with the TL1A isoform ratio, the higher the level of the proxy marker in an IBD patient, the higher the probability that the IBD patient will have a positive therapeutic response to an anti-TL1A treatment. Conversely, when the proxy marker moves in the same direction as the TL1A isoform ratio with regard to increased probability of positive therapeutic response to an anti-TL1A treatment in IBD patients. Accordingly, when the proxy marker has a negative correlation with the TL1A isoform ratio, the higher the level of the proxy marker in an IBD patient, the higher the probability that the IBD patient will have a positive therapeutic response to an anti-TL1A treatment.

[0182] In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the method further comprises preparing DNA from the sample.

[0183] In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the correlation is Pearson correlation or Spearman correlation. In some embodiments, the correlation is Pearson correlation. In certain embodiments, the correlation is Spearman correlation.

[0184] The term “proxy marker” refers to a marker having statistically significant correlation with TL1A isoform ratio at least in a subrange of the TL1A isoform ratio and thus having information for selecting patients having positive therapeutic response to anti-TL1A treatment, because the TL1A isoform ratio itself provides information for selecting patients having positive therapeutic response to anti-TL1A treatment as demonstrated in Examples. Such proxy maker can have statistically significant correlation with TL1A isoform ratio over just a subrange of such the TL1A isoform ratio, so long as such subrange statistically distinguishes the population with high TL1Ashort / TL1Alongratio from the population with low TL1Ashort / TL1Alongratio. In some embodiments, the proxy marker has statistically significant correlation with such TL1Ashort / TL1Alongratio at least in a subrange that encompasses the mean or median of the TL1Ashort / TL1Along ratio. In some embodiments, the proxy marker has statistically significant correlation with such TL1Ashort / TL1Alongratio at least in a subrange that encompasses the 2nd and 3rd quartile of the TL1Ashort / TL1Along ratio. In some embodiments, the proxy marker has statistically significant correlation such TL1Ashort / TL1Along ratio at least in a subrange that encompasses the 2nd quartile of the TL1Ashort / TL1Along ratio. In some embodiments, the proxy25743 marker has statistically significant correlation with such TL1Ashort / TL1Along ratio at least in a subrange that encompasses the 3rd quartile of the TL1Ashort / TL1Alongratio. Accordingly, such proxy marker can be used in lieu of the TL1A isoform ratio for selecting patients having positive therapeutic response to anti-TL1A treatment. In some examples of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the proxy marker is a serological marker. In some examples of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the proxy marker is a genetic marker. In some examples of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the proxy marker is a histology marker. In some examples of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the proxy marker is a protein marker. In some examples of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the proxy marker is a gene expression marker. In some examples of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the proxy marker is a protein expression marker. In some examples of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the proxy marker is a mRNA marker. In some examples of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the proxy marker is a single nucleotide polymorphism. In some examples of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the proxy marker is rs6478109. In some embodiments, if the proxy marker and the TL1A isoform ratio has a positive correlation (such proxy marker as “positive proxy marker”), the higher the level of the proxy marker the higher the probability the patients can have a positive therapeutic response to anti- TL1A treatment; and if the proxy marker and the TL1A isoform ratio has a negative correlation (such proxy marker as “inverse proxy marker”), the higher the level of the proxy marker the lower the probability the patients can have a positive therapeutic response to anti-TL1A treatment.

[0185] Accordingly, the TL1A isoform ratio and / or the proxy marker can be used to indicate the probability of the patient having a therapeutic response to the treatment of an TL1A inhibitor, with higher TL1A isoform ratio indicating higher probability of the patient having a therapeutic response and lower TL1A isoform ratio indicating lower probability of the patient having a therapeutic response. In some examples of the methods provided herein, the TL1A isoform ratio can be used as the basis for binarily classifying a patient as a responder (CDx positive) or non-25743 responder (CDx negative). The cutoff of the TL1A isoform ratio for determining such binary classification of the patient can be determined by training the model with the therapeutic response data from a patient cohort such that the TL1A isoform ratio cutoff provide the highest accuracy for classifying the responder, the non-responder, or both the responder and the non- responder, as described elsewhere in this disclosure. Such TL1A isoform ratio cutoff can also be determined by other machine learning or computerized clustering methods known and practiced in the art and as described elsewhere in this disclosure. In other examples, the mathematical function (e.g. coefficients in the function) used to calculate the TL1A isoform ratio from patient’s samples can be trained and normalized such that the TL1A isoform ratio has a range of 0 to 1 and 0.5 is cutoff for optimally classifying patient as a responder (CDx positive) or non-responder (CDx negative) to TL1A inhibitor treatment. In one specific example, the TL1A isoform ratio is calculated as TL1Ashort / TL1Along, wherein TL1Ashortis an expression level of the TL1A short isoform, TL1Along is an expression level of the TL1A long isoform. In another specific example, the TL1A isoform ratio is calculated as ln(TL1Ashort / TL1Along). In yet another specific example, the TL1A isoform ratio is calculated as ln(TL1Ashort / TL1Along+n), wherein n is a positive number. In general, if the TL1A isoform ratio is Ӌ cutoff, the prediction is "yes, responder" and CDx positive and if the TL1A isoform ratio is <cutoff, the prediction is "no, non-responder" and CDx negative.

[0186] Similarly and as is already clear from the description herein, the proxy marker can be used to indicate the probability of the patient having a therapeutic response to the treatment of an TL1A inhibitor. If the proxy marker has a positive correlation with TL1A isoform ratio, the higher proxy marker level indicates higher probability of the patient having a therapeutic response and lower proxy marker level indicates lower probability of the patient having a therapeutic response. If the proxy marker has a negative correlation with TL1A isoform ratio, the higher proxy marker level indicates lower probability of the patient having a therapeutic response and lower proxy marker level indicates higher probability of the patient having a therapeutic response. In some examples of the methods provided herein, the proxy marker can be used as the basis for binarily classifying a patient as a responder (CDx positive) or non- responder (CDx negative). The cutoff of the proxy marker for determining such binary classification of the patient can be determined by training the model with the therapeutic response data from a patient cohort such that the proxy marker cutoff provides the highest accuracy for classifying the responder, the non-responder, or both the responder and the non-25743 responder, as described elsewhere in this disclosure. Such proxy marker cutoff can also be determined by other machine learning or computerized clustering methods known and practiced in the art and as described elsewhere in this disclosure. In other examples, the mathematical function (e.g. coefficients in the function) used to calculate the proxy marker from patient’s samples can be trained and normalized such that the proxy marker has a range of 0 to 1 and 0.5 is cutoff for optimally classifying patient as a responder (CDx positive) or non-responder (CDx negative) to TL1A inhibitor treatment. In general, when the proxy marker has a positive correlation with TL1A isoform ratio, then: if the proxy marker is Ӌ cutoff, the prediction is "yes, responder" and CDx positive and if the proxy marker is <cutoff, the prediction is "no, non- responder" and CDx negative. When the proxy marker has a negative correlation with TL1A isoform ratio, then: if the proxy marker is > cutoff, the prediction is "no, non-responder" and CDx negative and if the proxy marker is ^cutoff, the prediction is "yes, responder" and CDx positive.

[0187] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the correlation between the proxy marker and the TL1A isoform ratio has a correlation coefficient with an absolute value of at least about 0.30, at least about 0.31, at least about 0.32, at least about 0.33, at least about 0.34, at least about 0.35, at least about 0.36, at least about 0.37, at least about 0.38, at least about 0.39, at least about 0.40, at least about 0.41, at least about 0.42, at least about 0.43, at least about 0.44, at least about 0.45, at least about 0.46, at least about 0.47, at least about 0.48, at least about 0.49, at least about 0.50, at least about 0.51, at least about 0.52, at least about 0.53, at least about 0.54, at least about 0.55, at least about 0.56, at least about 0.57, at least about 0.58, at least about 0.59, at least about 0.60, at least about 0.61, at least about 0.62, at least about 0.63, at least about 0.64, at least about 0.65, at least about 0.66, at least about 0.67, at least about 0.68, at least about 0.69, at least about 0.70, at least about 0.71, at least about 0.72, at least about 0.73, at least about 0.74, at least about 0.75, at least about 0.76, at least about 0.77, at least about 0.78, at least about 0.79, at least about 0.81, at least about 0.82, at least about 0.83, at least about 0.84, at least about 0.85, at least about 0.86, at least about 0.87, at least about 0.88, at least about 0.89, at least about 0.90, at least about 0.91, at least about 0.92, at least about 0.93, at least about 0.94, at least about 0.95, at least about 0.96, at least about 0.97, at least about 0.98, at least about 0.99, or 1. In other embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the correlation between the proxy marker and the TL1A isoform ratio has a correlation coefficient with an absolute value of about 0.30, about 0.31,25743 about 0.32, about 0.33, about 0.34, about 0.35, about 0.36, about 0.37, about 0.38, about 0.39, about 0.40, about 0.41, about 0.42, about 0.43, about 0.44, about 0.45, about 0.46, about 0.47, about 0.48, about 0.49, about 0.50, about 0.51, about 0.52, about 0.53, about 0.54, about 0.55, about 0.56, about 0.57, about 0.58, about 0.59, about 0.60, about 0.61, about 0.62, about 0.63, about 0.64, about 0.65, about 0.66, about 0.67, about 0.68, about 0.69, about 0.70, about 0.71, about 0.72, about 0.73, about 0.74, about 0.75, about 0.76, about 0.77, about 0.78, about 0.79, about 0.81, about 0.82, about 0.83, about 0.84, about 0.85, about 0.86, about 0.87, about 0.88, about 0.89, about 0.90, about 0.91, about 0.92, about 0.93, about 0.94, about 0.95, about 0.96, about 0.97, about 0.98, about 0.99, or 1.

[0188] The statistical significance of the correlation can be evaluated by p value calculated from statistical tests. Accordingly, in some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the statistical significance of the correlation between the proxy marker and the TL1A isoform ratio is determined by p value no more than 0.1 in a statistical test. In some embodiments, the statistical significance of the correlation between the proxy marker and the TL1A isoform ratio is determined by p value no more than 0.09 in a statistical test. In some embodiments, the statistical significance of the correlation between the proxy marker and the TL1A isoform ratio is determined by p value no more than 0.08 in a statistical test. In some embodiments, the statistical significance of the correlation between the proxy marker and the TL1A isoform ratio is determined by p value no more than 0.07 in a statistical test. In some embodiments, the statistical significance of the correlation between the proxy marker and the TL1A isoform ratio is determined by p value no more than 0.06 in a statistical test. In some embodiments, the statistical significance of the correlation between the proxy marker and the TL1A isoform ratio is determined by p value no more than 0.05 in a statistical test. In some embodiments, the statistical significance of the correlation between the proxy marker and the TL1A isoform ratio is determined by p value no more than 0.04 in a statistical test. In some embodiments, the statistical significance of the correlation between the proxy marker and the TL1A isoform ratio is determined by p value no more than 0.03 in a statistical test. In some embodiments, the statistical significance of the correlation between the proxy marker and the TL1A isoform ratio is determined by p value no more than 0.02 in a statistical test. In some embodiments, the statistical significance of the correlation between the proxy marker and the TL1A isoform ratio is determined by p value no more than 0.01 in a statistical test. In some embodiments of the various methods provided herein, including in25743 Sections 2, 5.1, and 7 and in this paragraph, the statistical test is an ANOVA test. In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7 and in this paragraph, the statistical test is a linear regression test. In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7 and in this paragraph, the statistical test is a logistic regression test. In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7 and in this paragraph, the statistical test is a T-test. In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7 and in this paragraph, the statistical test is Pearson correlation test. In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7 and in this paragraph, the statistical test is a Chi-square test.

[0189] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of at least about 0.6. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of at least about 0.65. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of at least about 0.7. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of at least about 0.75. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of at least about 0.8. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of at least about 0.85. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of at least about 0.9. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of at least about 0.95. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of at least about 0.99.

[0190] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of at most about -0.6. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of25743 at most about -0.65. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of at most about -0.7. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of at most about - 0.75. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of at most about -0.8. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of at most about -0.85. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of at most about -0.9. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of at most about -0.95. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of at most about -0.99.

[0191] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of about 0.6. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of about 0.65. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of about 0.7. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of about 0.75. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of about 0.8. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of about 0.85. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of about 0.9. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of about 0.95. In some embodiments of the various methods provided herein, the proxy marker positively correlates with TL1A isoform ratio with a correlation coefficient of about 0.99.

[0192] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of about -0.6. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of about -0.65. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of about -0.7. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of about -0.75. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of about -0.8. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of about -0.85. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of about -0.9. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of about -0.95. In some embodiments of the various methods provided herein, the proxy marker negatively correlates with TL1A isoform ratio with a correlation coefficient of about -0.99.

[0193] In one aspect, provided herein is a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant correlation with the TL1A isoform ratio.

[0194] In one aspect, provided herein is a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects;(c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant correlation with the TL1A isoform ratio, wherein the proxy marker relative to a cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition.

[0195] In one aspect, provided herein is a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant correlation with the TL1A isoform ratio, wherein the proxy marker and the TL1A isoform ratio has a positive correlation.

[0196] In one aspect, provided herein is a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant correlation with the TL1A isoform ratio, wherein the proxy marker relative to a cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition and wherein the proxy marker and the TL1A isoform ratio has a positive correlation.

[0197] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker is identified by a method of identifying a proxy marker for a ratio25743 between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant correlation with the TL1A isoform ratio.

[0198] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker is identified by a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant correlation with the TL1A isoform ratio wherein the proxy marker and the TL1A isoform ratio has a positive correlation.

[0199] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker is identified by a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant correlation with the TL1A isoform ratio, wherein the proxy marker relative to a cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition.25743

[0200] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker is identified by a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant correlation with the TL1A isoform ratio, wherein the proxy marker relative to a cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition and wherein the proxy marker and the TL1A isoform ratio has a positive correlation.

[0201] In one aspect, provided herein is a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant correlation with the TL1A isoform ratio, wherein the proxy marker and the TL1A isoform ratio has a negative correlation.

[0202] In one aspect, provided herein is a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the25743 marker has a statistically significant correlation with the TL1A isoform ratio, wherein the proxy marker relative to a cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition and wherein the proxy marker and the TL1A isoform ratio has a negative correlation.

[0203] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker is identified by a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant correlation with the TL1A isoform ratio wherein the proxy marker and the TL1A isoform ratio has a negative correlation.

[0204] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker is identified by a method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant correlation with the TL1A isoform ratio, wherein the proxy marker relative to a cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition and wherein the proxy marker and the TL1A isoform ratio has a negative correlation.25743

[0205] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the element “based on the TL1A isoform ratio” in the method is based on TL1A isoform ratio above a cutoff.

[0206] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the element “TL1A isoform ratio relative to the cutoff” in the method is the TL1A isoform ratio above the cutoff.

[0207] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker comprises rs6478109. In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker comprises rs6478109 with one or two risk alleles. In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker comprises rs6478109 with one or two minor alleles. In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker comprises rs6478109 with one or two risk alleles, wherein the risk allele comprises an A at the nucleoposition of polymorphism. In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the proxy marker comprises rs6478109 with one or two minor alleles, wherein the minor allele comprises an A at the nucleoposition of polymorphism.

[0208] As is already clear from the description herein, when the proxy marker comprises a SNP, the SNP can be converted into numerical number and a CDx positive or CDx negative determination can be made according to the proxy marker above a cutoff. For example, the polymorphisms can be mathematically represented as: (i) 0 for homozygous nonrisk alleles, 1 for heterozygous nonrisk and risk alleles, and 2 for homozygous risk alleles; (ii) 1 for homozygous nonrisk alleles, 1 for heterozygous nonrisk and risk alleles, and 0 for homozygous risk alleles; (iii) 0 for homozygous nonrisk alleles, 1 for heterozygous nonrisk and risk alleles, and 1 for homozygous risk alleles; (iv) 0 for homozygous nonrisk alleles, 0 for heterozygous nonrisk and risk alleles, and 1 for homozygous risk alleles; (v) 1 for homozygous nonrisk alleles, 0 for heterozygous nonrisk and risk alleles, and 0 for homozygous risk alleles; (vi) 2 for homozygous nonrisk alleles, 1 for heterozygous nonrisk and risk alleles, and 0 for homozygous risk alleles; and / or (vii) 0 for homozygous nonrisk alleles, 1 for heterozygous nonrisk and risk alleles, and 0 for homozygous risk alleles. When the proxy marker has positive correlation with the TL1A isoform ratio, e.g. the proxy marker comprising rs6478109 that is encoded as (i) or (iii) in the 2ndclause of this paragraph, proxy marker above 0 (rs6478109=1 or 2) could be used to select25743 patients having a positive therapeutic response to anti-TL1A treatment (in which case the cutoff=0). When the proxy marker has positive correlation with the TL1A isoform ratio, e.g. the proxy marker comprising rs6478109 that is encoded as (vi) in the 2ndclause of this paragraph, proxy marker below 2 (rs6478109=1 or 0) could be used to select patients having a positive therapeutic response to anti-TL1A treatment (in which case the cutoff=2). Additionally, when the proxy marker has positive correlation with the TL1A isoform ratio, e.g. the proxy marker comprising rs6478109 that is encoded as (v) in the 2ndclause of this paragraph, proxy marker below 1 (rs6478109=0) could be used to select patients having a positive therapeutic response to anti-TL1A treatment (in which case the cutoff=1).

[0209] In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the methods comprise interpreting the TL1A isoform ratio, the proxy marker, or the combination thereof. In some embodiments, the interpreting step is performed by an interpretation software. In certain embodiments, the interpretation software is as described in Sections 5.6.1, 5.6.2, 5.6.3, 5.6.4, and 5.6.5. In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the methods comprise interpreting the TL1A isoform ratio, the proxy marker, or the combination thereof with an interpretation software. In certain embodiments, the step of interpreting the TL1A isoform ratio, the proxy marker, or the combination thereof is any embodiment of such interpreting step as described in Sections 5.6.1, 5.6.2, 5.6.3, 5.6.4, and 5.6.5. In some embodiments, the step of interpreting the TL1A isoform ratio, the proxy marker, or the combination thereof is performed with the software as described in Sections 5.6.1, 5.6.2, 5.6.3, 5.6.4, and 5.6.5. In some embodiments, the step of interpreting the TL1A isoform ratio, the proxy marker, or the combination thereof is performed in a system as described in Sections 5.6.1, 5.6.2, 5.6.3, 5.6.4, and 5.6.5. In some embodiments, the step of interpreting the TL1A isoform ratio, the proxy marker, or the combination thereof is performed with a software as described in Sections 5.6.1, 5.6.2, 5.6.3, 5.6.4, and 5.6.5 and in a system as described in Sections 5.6.1, 5.6.2, 5.6.3, 5.6.4, and 5.6.5.

[0210] In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the method further comprises preparing nucleic acid from the sample obtained from the subject. In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the method further comprises preparing RNA from the sample obtained from the subject. In various embodiments of the25743 methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the method further comprises preparing proteins from the sample obtained from the subject. In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the method further comprises isolating nucleic acid from the sample obtained from the subject. In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the method further comprises isolating RNA from the sample obtained from the subject. In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the method further comprises isolating proteins from the sample obtained from the subject.

[0211] In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the method further comprises contacting the sample with one or more probes adapted to detect the presence of TL1A long isoform RNA, TL1A short isoform RNA, TL1A long isoform protein, and, TL1A short isoform protein. In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the method further comprises contacting the sample with an assay adapted to detect TL1A long isoform RNA and TL1A short isoform RNA. In some embodiments, the method further comprises contacting the sample with an assay adapted to detect TL1A long isoform protein and TL1A short isoform protein. In some embodiments, the method further comprises contacting the sample with an assay adapted to detect TL1A long isoform RNA and TL1A short isoform protein. In some embodiments, the method further comprises contacting the sample with an assay adapted to detect TL1A long isoform protein and TL1A short isoform RNA.

[0212] In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the method further comprises processing the sample to enrich the RNA. In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the method further comprises processing the sample to enrich the protein. In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the method further comprises processing the sample to enrich the TL1A RNA. In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the method further comprises processing the sample to enrich the TL1A protein.25743

[0213] As is already clear from the descriptions above and below, inverse proxy marker has a negative correlation with the TL1A isoform ratio, therefore patients having a positive therapeutic response to anti-TL1A treatment have the lower level of inverse proxy marker and thus are selected when the inverse proxy marker is below a cutoff. Accordingly, as a result of the negative correlation between the inverse proxy marker and the TL1A isoform ratio, the higher TL1A isoform ratio and the prediction of such higher TL1A isoform ratio can be approximated by lower level of inverse proxy marker. As such, in various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, TL1A isoform ratio or a positive proxy marker above a cutoff is determined if an inverse-proxy marker is below an alternative cutoff, wherein the inverse proxy marker has a negative correlation with the TL1A isoform ratio. In some embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the inverse proxy marker comprises the ratio of TL1A long isoform to the TL1A short isoform (the reciprocal of TL1A isoform ratio). In some embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the TL1A isoform ratio above a cutoff is determined if the ratio of TL1A long isoform to the TL1A short isoform (the reciprocal of TL1A isoform ratio) is below an alternative cutoff. In certain embodiments, the alternative cutoff for the inverse proxy marker can be determined in correspondence to the cutoff for the TL1A isoform ratio based on the correlation between the inverse proxy marker and TL1A isoform ratio.

[0214] In some embodiments of the methods provided herein, including in Sections 2, 5.1, and 7, the cutoff ranges from about 0.090 to about 0.110. In some embodiments of the methods provided herein, including in Sections 2, 5.1, and 7, the cutoff is about 0.097. In some embodiment of the methods provided herein, including in this paragraph, the cutoff is for selecting CD patients. Specifically, in some embodiments of the methods provided herein, including in Sections 2, 5.1, and 7, the cutoff for TL1A isoform ratio ranges from about 0.090 to about 0.110 for selecting CD patients that can have a positive therapeutic response to treatment with an inhibitor of TL1A expression or activity. In some embodiments of the methods provided herein, including in Sections 2, 5.1, and 7, the cutoff for TL1A isoform ratio is about 0.097 for selecting CD patients that can have a positive therapeutic response to treatment with an inhibitor of TL1A expression or activity.

[0215] In some embodiments of the methods provided herein, including in Sections 2, 5.1, and 7, the cutoff ranges from about 0.080 to about 0.10. In some embodiments of the methods25743 provided herein, including in Sections 2, 5.1, and 7, the cutoff is about 0.085. In some embodiment of the methods provided herein, including in this paragraph, the cutoff is for selecting UC patients. Specifically, in some embodiments of the methods provided herein, including in Sections 2, 5.1, and 7, the cutoff for TL1A isoform ratio ranges from about 0.080 to about 0.10 for selecting UC patients that can have a positive therapeutic response to treatment with an inhibitor of TL1A expression or activity. In some embodiments of the methods provided herein, including in Sections 2, 5.1, and 7, the cutoff for TL1A isoform ratio is about 0.085 for selecting UC patients that can have a positive therapeutic response to treatment with an inhibitor of TL1A expression or activity.

[0216] In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the cutoff is (i) the TL1A isoform ratio or proxy marker level in a heathy subject without the inflammatory, fibrotic, or fibrostenotic disease or condition or (ii) the TL1A isoform ratio or proxy marker level in a tissue not afflicted by the inflammatory, fibrotic, or fibrostenotic disease or condition. In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the cutoff is the TL1A isoform ratio or proxy marker level in a heathy subject without the inflammatory, fibrotic, or fibrostenotic disease or condition. In some embodiments of the various methods provided herein, including in Sections 2, 5.1, and 7, the cutoff is the TL1A isoform ratio or proxy marker level in a tissue not afflicted by the inflammatory, fibrotic, or fibrostenotic disease or condition.

[0217] The TL1A isoform ratio can be calculated directly as the ratio of the level of TL1A short isoform over the level of TL1A long isoform or some mathematical operation of such ratio. In some embodiments of the methods provided herein, including in Sections 2, 5.1, and 7, the TL1A isoform ratio is calculated as, TL1Ashort / TL1Along, ln(TL1Ashort / TL1Along), or ln(TL1Ashort / TL1Along+n), wherein TL1Ashort is an expression level of the TL1A short isoform, TL1Alongis an expression level of the TL1A long isoform, and n is a positive number. In some embodiments of the methods provided herein, including in Sections 2, 5.1, and 7, the TL1A isoform ratio is calculated as TL1Ashort / TL1Along, wherein TL1Ashortis an expression level of the TL1A short isoform, TL1Along is an expression level of the TL1A long isoform. In some embodiments of the methods provided herein, including in Sections 2, 5.1, and 7, the TL1A isoform ratio is calculated as ln(TL1Ashort / TL1Along), wherein TL1Ashort is an expression level of the TL1A short isoform, TL1Along is an expression level of the TL1A long isoform. In some embodiments of the methods provided herein, including in Sections 2, 5.1, and 7, the TL1A25743 isoform ratio is calculated as ln(TL1Ashort / TL1Along + n), wherein TL1Ashort is an expression level of the TL1A short isoform, TL1Alongis an expression level of the TL1A long isoform and “n” is a positive number. In some embodiments of the methods provided herein, including in Sections 2, 5.1, and 7, n is 1.

[0218] The level of TL1A long or TL1A short isoforms used in the determination of TL1A isoform ratio can be TL1A mRNA level (gene expression), TL1A protein level (protein expression), or a combination of the two. Accordingly, in one embodiment of the methods provided herein, including in Sections 2, 5.1, and 7, the expression level of the TL1A short isoform is the level of gene expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of gene expression of the TL1A long isoform. In another embodiment of the methods provided herein, including in Sections 2, 5.1, and 7, the expression level of the TL1A short isoform is the level of protein expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of protein expression of the TL1A long isoform. In a further embodiment of the methods provided herein, including in Sections 2, 5.1, and 7, the expression level of the TL1A short isoform is the level of gene expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of protein expression of the TL1A long isoform. In yet another embodiment of the methods provided herein, including in Sections 2, 5.1, and 7, the expression level of the TL1A short isoform is the level of protein expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of gene expression of the TL1A long isoform. Furthermore, in one embodiment of the methods provided herein, including in Sections 2, 5.1, and 7, the expression level of the TL1A short isoform is the gene expression level. In one embodiment of the methods provided herein, including in Sections 2, 5.1, and 7, the expression level of the TL1A short isoform is the protein expression level. In one embodiment of the methods provided herein, including in Sections 2, 5.1, and 7, the expression level of the TL1A long isoform is the gene expression level. In one embodiment of the methods provided herein, including in Sections 2, 5.1, and 7, the expression level of the TL1A long isoform is the protein expression level. Gene expression in

[0219] In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 25%. The other embodiments described25743 in this paragraph are provided for the various methods described herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 26%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 27%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 28%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 29%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 30%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 31%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 32%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 33%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 34%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 35%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 40%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 45%. In some embodiments, the TL1A isoform ratio or the25743 proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 50%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 51%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 55%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 60%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 65%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 70%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 75%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 80%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 85%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 90%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 25%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 26%. In some25743 embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 27%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 28%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 29%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 30%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 31%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 32%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 33%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 34%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 35%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 40%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 45%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 50%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a25743 positive predictive value of about 51%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 55%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 60%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 65%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 70%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 75%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 80%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 85%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 90%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value from 25% to 95%, from 30% to 95%, from 35% to 95%, from 40% to 95%, from 45% to 95%, from 50% to 95%, from 55% to 95%, from 60% to 95%, from 65% to 95%, from 70% to 95%, from 75% to 95%, from 80% to 95%, from 85% to 95%, from 90% to 95%, from 25% to 90%, from 30% to 90%, from 35% to 90%, from 40% to 90%, from 45% to 90%, from 50% to 90%, from 55% to 90%, from 60% to 90%, from 65% to 90%, from 70% to 90%, from 75% to 90%, from 80% to 90%, from 85% to 90%, from 25% to 85%, from 30% to 85%, from 35% to 85%, from 40% to 85%, from 45% to 85%, from 50% to 85%, from 55% to25743 85%, from 60% to 85%, from 65% to 85%, from 70% to 85%, from 75% to 85%, from 80% to 85%, from 25% to 80%, from 30% to 80%, from 35% to 80%, from 40% to 80%, from 45% to 80%, from 50% to 80%, from 55% to 80%, from 60% to 80%, from 65% to 80%, from 70% to 80%, from 75% to 80%, from 25% to 75%, from 30% to 75%, from 35% to 75%, from 40% to 75%, from 45% to 75%, from 50% to 75%, from 55% to 75%, from 60% to 75%, from 65% to 75%, from 70% to 75%, from 25% to 70%, from 30% to 70%, from 35% to 70%, from 40% to 70%, from 45% to 70%, from 50% to 70%, from 55% to 70%, from 60% to 70%, from 65% to 70%, from 25% to 65%, from 30% to 65%, from 35% to 65%, from 40% to 65%, from 45% to 65%, from 50% to 65%, from 55% to 65%, from 60% to 65%, from 25% to 60%, from 30% to 60%, from 35% to 60%, from 40% to 60%, from 45% to 60%, from 50% to 60%, from 55% to 60%, from 25% to 55%, from 30% to 55%, from 35% to 55%, from 40% to 55%, from 45% to 55%, from 50% to 55%, from 25% to 50%, from 30% to 50%, from 35% to 50%, from 40% to 50%, from 45% to 50%, from 25% to 45%, from 30% to 45%, from 35% to 45%, from 40% to 45%, from 25% to 40%, from 30% to 40%, from 35% to 40%, from 25% to 35%, from 30% to 35%, or from 25% to 30%. As is clear from the description, the element “the TL1A isoform ratio or the proxy marker is predictive of” means that each embodiment described in this paragraph further includes two embodiments with one reciting “the TL1A isoform ratio is predictive of” and the other reciting “the proxy marker is predictive of.” Furthermore, for each embodiment described in this paragraph, the element “the proxy marker is predictive of” is (i) “the proxy marker above a cutoff is predictive of” if the proxy marker and the TL1A isoform ratio has a positive correlation, or (ii) “the proxy marker below a cutoff is predictive of” if the proxy marker and the TL1A isoform ratio has a negative correlation. Additionally, for each embodiment described in this paragraph, an additional embodiment is provided wherein the element “the TL1A isoform ratio is predictive of” is “the TL1A isoform ratio above a cutoff is predictive of.”

[0220] Accordingly, in various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 25%. The other embodiments described in this paragraph are provided for the various methods described herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 26%. In25743 some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 27%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 28%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 29%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 30%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 31%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 32%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 33%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 34%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 35%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 40%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 45%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 50%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of atleast 51%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 55%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 60%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 65%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 70%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 75%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 80%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 85%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 90%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least 95%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 25%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 26%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 27%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity orexpression with a positive predictive value of about 28%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 29%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 30%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 31%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 32%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 33%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 34%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 35%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 40%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 45%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 50%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 51%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 55%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a25743 treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 60%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 65%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 70%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 75%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 80%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 85%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 90%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of about 95%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value from 25% to 95%, from 30% to 95%, from 35% to 95%, from 40% to 95%, from 45% to 95%, from 50% to 95%, from 55% to 95%, from 60% to 95%, from 65% to 95%, from 70% to 95%, from 75% to 95%, from 80% to 95%, from 85% to 95%, from 90% to 95%, from 25% to 90%, from 30% to 90%, from 35% to 90%, from 40% to 90%, from 45% to 90%, from 50% to 90%, from 55% to 90%, from 60% to 90%, from 65% to 90%, from 70% to 90%, from 75% to 90%, from 80% to 90%, from 85% to 90%, from 25% to 85%, from 30% to 85%, from 35% to 85%, from 40% to 85%, from 45% to 85%, from 50% to 85%, from 55% to 85%, from 60% to 85%, from 65% to 85%, from 70% to 85%, from 75% to 85%, from 80% to 85%, from 25% to 80%, from 30% to 80%, from 35% to 80%, from 40% to 80%, from 45% to 80%, from 50% to 80%, from 55% to 80%, from 60% to 80%, from 65% to 80%, from 70% to 80%, from 75% to 80%, from 25% to 75%, from 30% to 75%, from 35% to 75%, from 40% to 75%, from 45% to 75%, from25743 50% to 75%, from 55% to 75%, from 60% to 75%, from 65% to 75%, from 70% to 75%, from 25% to 70%, from 30% to 70%, from 35% to 70%, from 40% to 70%, from 45% to 70%, from 50% to 70%, from 55% to 70%, from 60% to 70%, from 65% to 70%, from 25% to 65%, from 30% to 65%, from 35% to 65%, from 40% to 65%, from 45% to 65%, from 50% to 65%, from 55% to 65%, from 60% to 65%, from 25% to 60%, from 30% to 60%, from 35% to 60%, from 40% to 60%, from 45% to 60%, from 50% to 60%, from 55% to 60%, from 25% to 55%, from 30% to 55%, from 35% to 55%, from 40% to 55%, from 45% to 55%, from 50% to 55%, from 25% to 50%, from 30% to 50%, from 35% to 50%, from 40% to 50%, from 45% to 50%, from 25% to 45%, from 30% to 45%, from 35% to 45%, from 40% to 45%, from 25% to 40%, from 30% to 40%, from 35% to 40%, from 25% to 35%, from 30% to 35%, or from 25% to 30%. Furthermore, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the cutoff is such that the TL1A isoform ratio above the cutoff is predictive of.” Furthermore, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the cutoff is such that the proxy marker above the cutoff is predictive of.”

[0221] In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 40%. The other embodiments described in this paragraph are provided for the various methods described herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 45%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 50%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 55%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 60%. In some embodiments, the TL1A25743 isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 65%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 70%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 75%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 80%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 85%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 90%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 40%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 45%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 50%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 55%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 60%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of25743 about 65%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 70%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 75%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 80%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 85%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 90%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value from 50% to 95%, from 55% to 95%, from 60% to 95%, from 65% to 95%, from 70% to 95%, from 75% to 95%, from 80% to 95%, from 85% to 95%, from 90% to 95%, from 50% to 90%, from 55% to 90%, from 60% to 90%, from 65% to 90%, from 70% to 90%, from 75% to 90%, from 80% to 90%, from 85% to 90%, from 50% to 85%, from 55% to 85%, from 60% to 85%, from 65% to 85%, from 70% to 85%, from 75% to 85%, from 80% to 85%, from 50% to 80%, from 55% to 80%, from 60% to 80%, from 65% to 80%, from 70% to 80%, from 75% to 80%, from 50% to 75%, from 55% to 75%, from 60% to 75%, from 65% to 75%, from 70% to 75%, from 50% to 70%, from 55% to 70%, from 60% to 70%, from 65% to 70%, from 50% to 65%, from 55% to 65%, from 60% to 65%, from 50% to 60%, from 55% to 60%, or from 50% to 55%. As is clear from the description, the element “the TL1A isoform ratio or the proxy marker is predictive of” means that each embodiment described in this paragraph further includes two embodiments with one reciting “the TL1A isoform ratio is predictive of” and the other reciting “the proxy marker is predictive of.” Furthermore, for each embodiment described in this paragraph, the element “the proxy marker is predictive of” is (i) “the proxy marker above a cutoff is predictive of” if the proxy marker and the TL1A isoform25743 ratio has a positive correlation, or (ii) “the proxy marker below a cutoff is predictive of” if the proxy marker and the TL1A isoform ratio has a negative correlation. Additionally, for each embodiment described in this paragraph, an additional embodiment is provided wherein the element “the TL1A isoform ratio is predictive of” is “the TL1A isoform ratio above a cutoff is predictive of.”

[0222] Accordingly, in various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 40%. The other embodiments described in this paragraph are provided for the various methods described herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 45%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 50%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 55%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 60%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 65%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 70%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 75%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 80%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or25743 expression with a negative predictive value of at least 85%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 90%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least 95%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 40%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 45%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 50%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 55%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 60%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 65%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 70%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 75%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 80%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 85%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a25743 treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 90%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of about 95%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value from 50% to 95%, from 55% to 95%, from 60% to 95%, from 65% to 95%, from 70% to 95%, from 75% to 95%, from 80% to 95%, from 85% to 95%, from 90% to 95%, from 50% to 90%, from 55% to 90%, from 60% to 90%, from 65% to 90%, from 70% to 90%, from 75% to 90%, from 80% to 90%, from 85% to 90%, from 50% to 85%, from 55% to 85%, from 60% to 85%, from 65% to 85%, from 70% to 85%, from 75% to 85%, from 80% to 85%, from 50% to 80%, from 55% to 80%, from 60% to 80%, from 65% to 80%, from 70% to 80%, from 75% to 80%, from 50% to 75%, from 55% to 75%, from 60% to 75%, from 65% to 75%, from 70% to 75%, from 50% to 70%, from 55% to 70%, from 60% to 70%, from 65% to 70%, from 50% to 65%, from 55% to 65%, from 60% to 65%, from 50% to 60%, from 55% to 60%, or from 50% to 55%. Furthermore, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the cutoff is such that the TL1A isoform ratio above the cutoff is predictive of.” Additionally, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the cutoff is such that the proxy marker the above the cutoff is predictive of.”

[0223] In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 20%. The other embodiments described in this paragraph are provided for the various methods described herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 25%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 30%. In some embodiments, the TL1A isoform ratio or the proxy marker is25743 predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 35%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 40%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 45%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 50%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 55%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 60%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 65%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 70%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 75%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 80%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 85%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 90%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with25743 the inhibitor of TL1A activity or expression with a sensitivity of about 20%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 25%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 30%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 35%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 40%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 45%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 50%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 55%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 60%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 65%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 70%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 75%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 80%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 85%. In some embodiments, the TL1A isoform ratio or the25743 proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 90%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity from 20% to 95%, from 25% to 95%, from 30% to 95%, from 35% to 95%, from 40% to 95%, from 45% to 95%, from 50% to 95%, from 55% to 95%, from 60% to 95%, from 65% to 95%, from 70% to 95%, from 75% to 95%, from 80% to 95%, from 85% to 95%, from 90% to 95%, from 20% to 90%, from 25% to 90%, from 30% to 90%, from 35% to 90%, from 40% to 90%, from 45% to 90%, from 50% to 90%, from 55% to 90%, from 60% to 90%, from 65% to 90%, from 70% to 90%, from 75% to 90%, from 80% to 90%, from 85% to 90%, from 20% to 85%, from 25% to 85%, from 30% to 85%, from 35% to 85%, from 40% to 85%, from 45% to 85%, from 50% to 85%, from 55% to 85%, from 60% to 85%, from 65% to 85%, from 70% to 85%, from 75% to 85%, from 80% to 85%, from 20% to 80%, from 25% to 80%, from 30% to 80%, from 35% to 80%, from 40% to 80%, from 45% to 80%, from 50% to 80%, from 55% to 80%, from 60% to 80%, from 65% to 80%, from 70% to 80%, from 75% to 80%, from 20% to 75%, from 25% to 75%, from 30% to 75%, from 35% to 75%, from 40% to 75%, from 45% to 75%, from 50% to 75%, from 55% to 75%, from 60% to 75%, from 65% to 75%, from 70% to 75%, from 20% to 70%, from 25% to 70%, from 30% to 70%, from 35% to 70%, from 40% to 70%, from 45% to 70%, from 50% to 70%, from 55% to 70%, from 60% to 70%, from 65% to 70%, from 20% to 65%, from 25% to 65%, from 30% to 65%, from 35% to 65%, from 40% to 65%, from 45% to 65%, from 50% to 65%, from 55% to 65%, from 60% to 65%, from 20% to 60%, from 25% to 60%, from 30% to 60%, from 35% to 60%, from 40% to 60%, from 45% to 60%, from 50% to 60%, from 55% to 60%, from 20% to 55%, from 25% to 55%, from 30% to 55%, from 35% to 55%, from 40% to 55%, from 45% to 55%, from 50% to 55%, from 20% to 50%, from 25% to 50%, from 30% to 50%, from 35% to 50%, from 40% to 50%, from 45% to 50%, from 20% to 45%, from 25% to 45%, from 30% to 45%, from 35% to 45%, from 40% to 45%, from 20% to 40%, from 25% to 40%, from 30% to 40%, from 35% to 40%, from 20% to 35%, from 25% to 35%, from 30% to 35%, from 20% to 30%, from 25% to 30%, or from 20% to 25%. As is clear from the description, the element “the TL1A isoform ratio or the proxy marker is predictive of” means that each embodiment described in this paragraph25743 further includes two embodiments with one reciting “the TL1A isoform ratio is predictive of” and the other reciting “the proxy marker is predictive of.” Furthermore, for each embodiment described in this paragraph, the element “the proxy marker is predictive of” is (i) “the proxy marker above a cutoff is predictive of” if the proxy marker and the TL1A isoform ratio has a positive correlation, or (ii) “the proxy marker below a cutoff is predictive of” if the proxy marker and the TL1A isoform ratio has a negative correlation. Additionally, for each embodiment described in this paragraph, an additional embodiment is provided wherein the element “the TL1A isoform ratio is predictive of” is “the TL1A isoform ratio above a cutoff is predictive of.”

[0224] Accordingly, in various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 20%. The other embodiments described in this paragraph are provided for the various methods described herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 25%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 30%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 35%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 40%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 45%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 50%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 55%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 60%. In25743 some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 65%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 70%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 75%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 80%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 85%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 90%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least 95%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 20%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 25%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 30%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 35%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 40%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 45%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a25743 sensitivity of about 50%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 55%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 60%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 65%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 70%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 75%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 80%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 85%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 90%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of about 95%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity from 20% to 95%, from 25% to 95%, from 30% to 95%, from 35% to 95%, from 40% to 95%, from 45% to 95%, from 50% to 95%, from 55% to 95%, from 60% to 95%, from 65% to 95%, from 70% to 95%, from 75% to 95%, from 80% to 95%, from 85% to 95%, from 90% to 95%, from 20% to 90%, from 25% to 90%, from 30% to 90%, from 35% to 90%, from 40% to 90%, from 45% to 90%, from 50% to 90%, from 55% to 90%, from 60% to 90%, from 65% to 90%, from 70% to 90%, from 75% to 90%, from 80% to 90%, from 85% to 90%, from 20% to 85%, from 25% to 85%, from 30% to 85%, from 35% to 85%, from 40% to 85%, from 45% to 85%, from 50% to 85%, from 55% to 85%, from 60% to 85%, from 65% to 85%, from 70% to 85%, from 75% to 85%, from 80% to 85%, from 20% to 80%, from 25% to 80%, from 30% to 80%,25743 from 35% to 80%, from 40% to 80%, from 45% to 80%, from 50% to 80%, from 55% to 80%, from 60% to 80%, from 65% to 80%, from 70% to 80%, from 75% to 80%, from 20% to 75%, from 25% to 75%, from 30% to 75%, from 35% to 75%, from 40% to 75%, from 45% to 75%, from 50% to 75%, from 55% to 75%, from 60% to 75%, from 65% to 75%, from 70% to 75%, from 20% to 70%, from 25% to 70%, from 30% to 70%, from 35% to 70%, from 40% to 70%, from 45% to 70%, from 50% to 70%, from 55% to 70%, from 60% to 70%, from 65% to 70%, from 20% to 65%, from 25% to 65%, from 30% to 65%, from 35% to 65%, from 40% to 65%, from 45% to 65%, from 50% to 65%, from 55% to 65%, from 60% to 65%, from 20% to 60%, from 25% to 60%, from 30% to 60%, from 35% to 60%, from 40% to 60%, from 45% to 60%, from 50% to 60%, from 55% to 60%, from 20% to 55%, from 25% to 55%, from 30% to 55%, from 35% to 55%, from 40% to 55%, from 45% to 55%, from 50% to 55%, from 20% to 50%, from 25% to 50%, from 30% to 50%, from 35% to 50%, from 40% to 50%, from 45% to 50%, from 20% to 45%, from 25% to 45%, from 30% to 45%, from 35% to 45%, from 40% to 45%, from 20% to 40%, from 25% to 40%, from 30% to 40%, from 35% to 40%, from 20% to 35%, from 25% to 35%, from 30% to 35%, from 20% to 30%, from 25% to 30%, or from 20% to 25%. Furthermore, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the cutoff is such that the TL1A isoform ratio above the cutoff is predictive of.” Additionally, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the cutoff is such that the proxy marker the above the cutoff is predictive of.”

[0225] In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 40%. The other embodiments described in this paragraph are provided for the various methods described herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 45%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 50%. In some embodiments, the TL1A isoform ratio or the proxy marker is25743 predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 55%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 60%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 65%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 70%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 75%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 80%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 85%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 90%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 40%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 45%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 50%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 55%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the25743 inhibitor of TL1A activity or expression with a specificity of about 60%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 65%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 70%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 75%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 80%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 85%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 90%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity from 50% to 95%, from 55% to 95%, from 60% to 95%, from 65% to 95%, from 70% to 95%, from 75% to 95%, from 80% to 95%, from 85% to 95%, from 90% to 95%, from 50% to 90%, from 55% to 90%, from 60% to 90%, from 65% to 90%, from 70% to 90%, from 75% to 90%, from 80% to 90%, from 85% to 90%, from 50% to 85%, from 55% to 85%, from 60% to 85%, from 65% to 85%, from 70% to 85%, from 75% to 85%, from 80% to 85%, from 50% to 80%, from 55% to 80%, from 60% to 80%, from 65% to 80%, from 70% to 80%, from 75% to 80%, from 50% to 75%, from 55% to 75%, from 60% to 75%, from 65% to 75%, from 70% to 75%, from 50% to 70%, from 55% to 70%, from 60% to 70%, from 65% to 70%, from 50% to 65%, from 55% to 65%, from 60% to 65%, from 50% to 60%, from 55% to 60%, or from 50% to 55%. As is clear from the description, the element “the TL1A isoform ratio or the proxy marker is predictive of” means that each embodiment described in this paragraph further includes two embodiments with one reciting “the TL1A isoform ratio is predictive of” and the other reciting “the proxy marker is predictive of.” Furthermore, for each embodiment25743 described in this paragraph, the element “the proxy marker is predictive of” is (i) “the proxy marker above a cutoff is predictive of” if the proxy marker and the TL1A isoform ratio has a positive correlation, or (ii) “the proxy marker below a cutoff is predictive of” if the proxy marker and the TL1A isoform ratio has a negative correlation. Additionally, for each embodiment described in this paragraph, an additional embodiment is provided wherein the element “the TL1A isoform ratio is predictive of” is “the TL1A isoform ratio above a cutoff is predictive of.”

[0226] Accordingly, in various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 40%. The other embodiments described in this paragraph are provided for the various methods described herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 45%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 50%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 55%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 60%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 65%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 70%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 75%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 80%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a25743 specificity of at least 85%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 90%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least 95%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 40%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 45%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 50%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 55%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 60%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 65%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 70%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 75%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 80%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 85%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of about 90%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or25743 expression with a specificity of about 95%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity from 50% to 95%, from 55% to 95%, from 60% to 95%, from 65% to 95%, from 70% to 95%, from 75% to 95%, from 80% to 95%, from 85% to 95%, from 90% to 95%, from 50% to 90%, from 55% to 90%, from 60% to 90%, from 65% to 90%, from 70% to 90%, from 75% to 90%, from 80% to 90%, from 85% to 90%, from 50% to 85%, from 55% to 85%, from 60% to 85%, from 65% to 85%, from 70% to 85%, from 75% to 85%, from 80% to 85%, from 50% to 80%, from 55% to 80%, from 60% to 80%, from 65% to 80%, from 70% to 80%, from 75% to 80%, from 50% to 75%, from 55% to 75%, from 60% to 75%, from 65% to 75%, from 70% to 75%, from 50% to 70%, from 55% to 70%, from 60% to 70%, from 65% to 70%, from 50% to 65%, from 55% to 65%, from 60% to 65%, from 50% to 60%, from 55% to 60%, or from 50% to 55%. Furthermore, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the cutoff is such that the TL1A isoform ratio above the cutoff is predictive of.” Additionally, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the cutoff is such that the proxy marker the above the cutoff is predictive of.”

[0227] In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least 10%. The other embodiments described in this paragraph are provided for the various methods described herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least 15%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least 20%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least 25%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least 30%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least 35%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least25743 40%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least 45%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least 50%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least 55%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least 60%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least 65%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least 70%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is at least 75%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is about 10%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is about 15%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is about 20%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is about 25%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is about 30%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is about 35%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is about 40%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is about 45%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is about 50%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is about 55%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is about 60%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is about 65%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is about 70%. In some embodiments, the positive rate of the subjects with the TL1A25743 isoform ratio or the proxy marker as provided in the methods is about 75%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is from 10% to 75%, from 15% to 75%, from 20% to 75%, from 25% to 75%, from 30% to 75%, from 35% to 75%, from 40% to 75%, from 45% to 75%, from 50% to 75%, from 55% to 75%, from 60% to 75%, from 65% to 75%, from 70% to 75%, 10% to 70%, from 15% to 70%, from 20% to 70%, from 25% to 70%, from 30% to 70%, from 35% to 70%, from 40% to 70%, from 45% to 70%, from 50% to 70%, from 55% to 70%, from 60% to 70%, from 65% to 70%, from10% to 65%, from 15% to 65%, from 20% to 65%, from 25% to 65%, from 30% to 65%, from 35% to 65%, from 40% to 65%, from 45% to 65%, from 50% to 65%, from 55% to 65%, from 60% to 65%, from 10% to 60%, from 15% to 60%, from 20% to 60%, from 25% to 60%, from 30% to 60%, from 35% to 60%, from 40% to 60%, from 45% to 60%, from 50% to 60%, from 55% to 60%, from 10% to 55%, from 15% to 55%, from 20% to 55%, from 25% to 55%, from 30% to 55%, from 35% to 55%, from 40% to 55%, from 45% to 55%, from 50% to 55%, from 10% to 50%, from 15% to 50%, from 20% to 50%, from 25% to 50%, from 30% to 50%, from 35% to 50%, from 40% to 50%, from 45% to 50%, from 10% to 45%, from 15% to 45%, from 20% to 45%, from 25% to 45%, from 30% to 45%, from 35% to 45%, from 40% to 45%, from 10% to 40%, from 15% to 40%, from 20% to 40%, from 25% to 40%, from 30% to 40%, from 35% to 40%, from 10% to 35%, from 15% to 35%, from 20% to 35%, from 25% to 35%, from 30% to 35%, from 10% to 30%, from 15% to 30%, from 20% to 30%, from 25% to 30%, from 10% to 25%, from 15% to 25%, from 20% to 25%, from 10% to 20%, from 15% to 20%, or from 10% to 15%. In some specific embodiments, the positive rate of the subjects with the TL1A isoform ratio or the proxy marker as provided in the methods is from 30% to 40%. As is clear from the description, the element “with the TL1A isoform ratio or the proxy marker” means that each embodiment described in this paragraph further includes two embodiments with one reciting “with the TL1A isoform ratio” and the other reciting “with the proxy marker.” Furthermore, for each embodiment described in this paragraph, the element “with the proxy marker” is (i) “with the proxy marker above a cutoff” if the proxy marker and the TL1A isoform ratio has a positive correlation, or (ii) “with the proxy marker below a cutoff” if the proxy marker and the TL1A isoform ratio has a negative correlation. Additionally, for each embodiment described in this paragraph, an additional embodiment is provided wherein the element “with the TL1A isoform ratio” is “with the TL1A isoform ratio above a cutoff.”25743

[0228] Accordingly, in various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 10%. The other embodiments described in this paragraph are provided for the various methods described herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 15%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 20%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 25%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 30%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 35%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 40%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 45%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 50%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 55%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 60%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 65%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 70%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is at least 75%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 10%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 15%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 20%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 25%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 30%. In some embodiments,25743 the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 35%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 40%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 45%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 50%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 55%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 60%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 65%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 70%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is about 75%. In some embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is from 10% to 75%, from 15% to 75%, from 20% to 75%, from 25% to 75%, from 30% to 75%, from 35% to 75%, from 40% to 75%, from 45% to 75%, from 50% to 75%, from 55% to 75%, from 60% to 75%, from 65% to 75%, from 70% to 75%, 10% to 70%, from 15% to 70%, from 20% to 70%, from 25% to 70%, from 30% to 70%, from 35% to 70%, from 40% to 70%, from 45% to 70%, from 50% to 70%, from 55% to 70%, from 60% to 70%, from 65% to 70%, from10% to 65%, from 15% to 65%, from 20% to 65%, from 25% to 65%, from 30% to 65%, from 35% to 65%, from 40% to 65%, from 45% to 65%, from 50% to 65%, from 55% to 65%, from 60% to 65%, from 10% to 60%, from 15% to 60%, from 20% to 60%, from 25% to 60%, from 30% to 60%, from 35% to 60%, from 40% to 60%, from 45% to 60%, from 50% to 60%, from 55% to 60%, from 10% to 55%, from 15% to 55%, from 20% to 55%, from 25% to 55%, from 30% to 55%, from 35% to 55%, from 40% to 55%, from 45% to 55%, from 50% to 55%, from 10% to 50%, from 15% to 50%, from 20% to 50%, from 25% to 50%, from 30% to 50%, from 35% to 50%, from 40% to 50%, from 45% to 50%, from 10% to 45%, from 15% to 45%, from 20% to 45%, from 25% to 45%, from 30% to 45%, from 35% to 45%, from 40% to 45%, from 10% to 40%, from 15% to 40%, from 20% to 40%, from 25% to 40%, from 30% to 40%, from 35% to 40%, from 10% to 35%, from 15% to 35%, from 20% to 35%, from 25% to 35%, from 30% to 35%, from 10% to 30%, from 15% to 30%, from 20% to 30%, from 25% to 30%, from 10% to 25%, from 15% to 25%,25743 from 20% to 25%, from 10% to 20%, from 15% to 20%, or from 10% to 15%. In some specific embodiments, the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods is from 30% to 40%. Furthermore, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods” is substituted by the phrase “the cutoff is such that the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods.” Additionally, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the positive rate of the subjects with the TL1A isoform ratio above the cutoff as provided in the methods” is substituted by the phrase “the cutoff is such that the positive rate of the subjects with the proxy marker above the cutoff as provided in the methods.”

[0229] As used herein, the term “positive rate,” when used in reference to a matter (e.g. in reference to subjects having TL1A isoform ratio above a cutoff or in reference to TL1A isoform ratio above a cutoff), means the percentage of the subjects or patients that are positive or determined to be positive for the matter (e.g. positive for having TL1A isoform ratio above a cutoff) over the whole subject or patient population. For another example, the positive rate of samples classified as having a TL1A isoform ratio above a cutoff means the percentage of samples classified as having a TL1A isoform ratio above a cutoff over the population of samples subjected to the classification. The term “negative rate,” when used in reference to a matter (e.g. in reference to subjects having TL1A isoform ratio above a cutoff or in reference to TL1A isoform ratio above a cutoff), means the percentage of the subjects or patients that are negative or determined to be negative for the matter (e.g. negative for having TL1A isoform ratio above a cutoff) over the whole subject or patient population. As a subject or a patient is either positive or negative for having a TL1A isoform ratio above a cutoff, the disclosure provides the corresponding embodiments for the negative rate of having TL1A isoform ratio above a cutoff, which negative rate is calculated as 100% minus the positive rate of having TL1A isoform ratio above the cutoff. Similarly, the disclosure provides the corresponding embodiments for the negative rate of having a proxy marker above a cutoff, which negative rate is calculated as 100% minus the positive rate of having proxy marker above the cutoff.

[0230] In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity25743 or expression with an accuracy of at least 50%. The other embodiments described in this paragraph are provided for the various methods described herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 55%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 60%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 65%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 70%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 75%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 80%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 85%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 90%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 50%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 55%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 60%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a25743 positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 65%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 70%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 75%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 80%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 85%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 90%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 95%. In some embodiments, the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of from 60% to 95%, from 65% to 95%, from 70% to 95%, from 75% to 95%, from 80% to 95%, from 85% to 95%, from 90% to 95%, from 60% to 90%, from 65% to 90%, from 70% to 90%, from 75% to 90%, from 80% to 90%, from 85% to 90%, from 60% to 85%, from 65% to 85%, from 70% to 85%, from 75% to 85%, from 80% to 85%, from 60% to 80%, from 65% to 80%, from 70% to 80%, from 75% to 80%, from 60% to 75%, from 65% to 75%, from 70% to 75%, from 60% to 70%, from 65% to 70%, or from 60% to 65%. As is clear from the description, the element “the TL1A isoform ratio or the proxy marker is predictive of” means that each embodiment described in this paragraph further includes two embodiments with one reciting “the TL1A isoform ratio is predictive of” and the other reciting “the proxy marker is predictive of.” Furthermore, for each embodiment described in this paragraph, the element “the proxy marker is predictive of” is (i) “the proxy marker above a cutoff is predictive of” if the proxy marker and the TL1A isoform ratio has a positive correlation, or (ii) “the proxy marker below a cutoff is predictive of” if the proxy marker and the TL1A isoform ratio has a negative correlation. Additionally, for each embodiment25743 described in this paragraph, an additional embodiment is provided wherein the element “the TL1A isoform ratio is predictive of” is “the TL1A isoform ratio above a cutoff is predictive of.”

[0231] Accordingly, in various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 50%. The other embodiments described in this paragraph are provided for the various methods described herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 55%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 60%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 65%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 70%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 75%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 80%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 85%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 90%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least 95%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 50%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with25743 the inhibitor of TL1A activity or expression with an accuracy of about 55%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 60%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 65%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 70%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 75%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 80%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 85%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 90%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of about 95%. In some embodiments, the TL1A isoform ratio above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of from 60% to 95%, from 65% to 95%, from 70% to 95%, from 75% to 95%, from 80% to 95%, from 85% to 95%, from 90% to 95%, from 60% to 90%, from 65% to 90%, from 70% to 90%, from 75% to 90%, from 80% to 90%, from 85% to 90%, from 60% to 85%, from 65% to 85%, from 70% to 85%, from 75% to 85%, from 80% to 85%, from 60% to 80%, from 65% to 80%, from 70% to 80%, from 75% to 80%, from 60% to 75%, from 65% to 75%, from 70% to 75%, from 60% to 70%, from 65% to 70%, or from 60% to 65%. Furthermore, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the cutoff is such that the TL1A isoform ratio above the cutoff is predictive of.” Additionally, for each embodiment described in this paragraph, also provided is a corresponding embodiment25743 wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the cutoff is such that the proxy marker the above the cutoff is predictive of.”

[0232] The term “accuracy,” when used in reference to a test for selecting patients for treatment or in the context of a performing metrics of a test for selecting patients for treatment, means the summation of the performance for correctly calling the true positive and correctly calling the true negatives. Accuracy can be calculated as (true positive + true negative) / (true positive + true negative + false positive + false negative)). Accuracy can also be calculated as the balanced accuracy, which is the geometric mean of recall, or sensitivity, across all labels or treatment response phenotypes.

[0233] In various embodiments of the methods provided herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 25%. The other embodiments described in this paragraph are provided for the various methods described herein including in Sections 2, 5.1 (e.g. the preceding paragraphs), and 7. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 26%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 27%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 28%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 29%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 30%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in25743 TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 31%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 32%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 33%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 34%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 35%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 40%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 45%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 50%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 51%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 55%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample25743 obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 60%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 65%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 70%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 75%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 80%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 85%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 90%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of at least 95%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 25%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 26%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as25743 compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 27%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 28%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 29%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 30%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 31%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 32%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 33%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 34%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 35%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 40%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of25743 TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 45%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 50%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 51%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 55%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 60%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 65%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 70%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 75%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 80%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 85%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level25743 in a tissue not affected by IBD) with a positive predictive value of about 90%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value of about 95%. In some embodiments, the TL1A isoform ratio above the cutoff predicts an increase in TL1A protein expression in a sample obtained from a subject as compared to a reference level of TL1A protein expression (e.g., level in a tissue not affected by IBD) with a positive predictive value from 25% to 95%, from 30% to 95%, from 35% to 95%, from 40% to 95%, from 45% to 95%, from 50% to 95%, from 55% to 95%, from 60% to 95%, from 65% to 95%, from 70% to 95%, from 75% to 95%, from 80% to 95%, from 85% to 95%, from 90% to 95%, from 25% to 90%, from 30% to 90%, from 35% to 90%, from 40% to 90%, from 45% to 90%, from 50% to 90%, from 55% to 90%, from 60% to 90%, from 65% to 90%, from 70% to 90%, from 75% to 90%, from 80% to 90%, from 85% to 90%, from 25% to 85%, from 30% to 85%, from 35% to 85%, from 40% to 85%, from 45% to 85%, from 50% to 85%, from 55% to 85%, from 60% to 85%, from 65% to 85%, from 70% to 85%, from 75% to 85%, from 80% to 85%, from 25% to 80%, from 30% to 80%, from 35% to 80%, from 40% to 80%, from 45% to 80%, from 50% to 80%, from 55% to 80%, from 60% to 80%, from 65% to 80%, from 70% to 80%, from 75% to 80%, from 25% to 75%, from 30% to 75%, from 35% to 75%, from 40% to 75%, from 45% to 75%, from 50% to 75%, from 55% to 75%, from 60% to 75%, from 65% to 75%, from 70% to 75%, from 25% to 70%, from 30% to 70%, from 35% to 70%, from 40% to 70%, from 45% to 70%, from 50% to 70%, from 55% to 70%, from 60% to 70%, from 65% to 70%, from 25% to 65%, from 30% to 65%, from 35% to 65%, from 40% to 65%, from 45% to 65%, from 50% to 65%, from 55% to 65%, from 60% to 65%, from 25% to 60%, from 30% to 60%, from 35% to 60%, from 40% to 60%, from 45% to 60%, from 50% to 60%, from 55% to 60%, from 25% to 55%, from 30% to 55%, from 35% to 55%, from 40% to 55%, from 45% to 55%, from 50% to 55%, from 25% to 50%, from 30% to 50%, from 35% to 50%, from 40% to 50%, from 45% to 50%, from 25% to 45%, from 30% to 45%, from 35% to 45%, from 40% to 45%, from 25% to 40%, from 30% to 40%, from 35% to 40%, from 25% to 35%, from 30% to 35%, or from 25% to 30%. In some embodiments of the methods provided herein including in this paragraph, the subject is a subject having IBD. In some embodiments of the methods provided herein including in this paragraph, the subject is a subject having UC. In some embodiments of the methods provided herein including in this paragraph, the subject is a subject having CD. Furthermore, for25743 each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the cutoff is such that the TL1A isoform ratio above the cutoff is predictive of.” Additionally, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the cutoff is such that the proxy marker the above the cutoff is predictive of.” Still further, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the TL1A isoform ratio is predictive of.” Furthermore, for each embodiment described in this paragraph, also provided is a corresponding embodiment wherein the phrase “the TL1A isoform ratio above the cutoff predicts” is substituted by the phrase “the proxy marker is predictive of.” Additionally, for the embodiment described in this paragraph, the element “the proxy marker is ...

Claims

25743 WHAT IS CLAIMED:

1. A method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, wherein the subject is selected based on a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof.

2. A method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; (ii) subjecting the sample to an assay adapted to determine a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof; (iii) determining the subject is suitable for treatment with an inhibitor of TL1A activity or expression based on the TL1A isoform ratio or the proxy marker; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

3. A method of determining a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”) or a proxy marker having a statistically significant correlation with the TL1A isoform ratio for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; and (c) determining a ratio TL1A isoform ratio, a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof,25743 wherein whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression is indicated based on the TL1A isoform ratio or the proxy marker.

4. A method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) obtaining or having obtained a sample from the subject; (b) subjecting the sample to an assay adapted to detect an expression level of the TL1A short isoform and an expression level of the TL1A long isoform; (c) determining a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), a proxy marker having a statistically significant correlation with the TL1A isoform ratio, or a combination thereof; and (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on the TL1A isoform ratio or the proxy marker.

5. The method of any one of claims 2 to 4, wherein the method further comprises preparing nucleic acids from the sample.

6. The method of any one of claims 1 to 5, wherein the correlation is Pearson correlation or Spearman correlation.

7. The method of claim 6, wherein the correlation has a correlation coefficient with an absolute value of at least about 0.30, at least about 0.31, at least about 0.32, at least about 0.33, at least about 0.34, at least about 0.35, at least about 0.36, at least about 0.37, at least about 0.38, at least about 0.39, at least about 0.40, at least about 0.41, at least about 0.42, at least about 0.43, at least about 0.44, at least about 0.45, at least about 0.46, at least about 0.47, at least about 0.48, at least about 0.49, at least about 0.50, at least about 0.51, at least about 0.52, at least about 0.53, at least about 0.54, at least about 0.55, at least about 0.56, at least about 0.57, at least about 0.58, at least about 0.59, at least about 0.60, at least about 0.61, at least about 0.62, at least about 0.63, at least about 0.64, at least about 0.65, at least about 0.66, at least about 0.67, at least about 0.68, at least about 0.69, at least about 0.70, at least about 0.71, at least about 0.72, at least about 0.73, at least about 0.74, at least about 0.75, at least about 0.76, at least about 0.77, at least about 0.78, at least about 0.79, at least about 0.81, at least about 0.82, at least about 0.83, at least25743 about 0.84, at least about 0.85, at least about 0.86, at least about 0.87, at least about 0.88, at least about 0.89, at least about 0.90, at least about 0.91, at least about 0.92, at least about 0.93, at least about 0.94, at least about 0.95, at least about 0.96, at least about 0.97, at least about 0.98, at least about 0.99, or 1.

8. A method of identifying a proxy marker for a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”), the method comprising: (a) determine the TL1A isoform ratio in a population of subjects; (b) determining a marker other than the TL1A isoform ratio in the population of subjects; (c) determining the correlation between the marker in (b) and the TL1A isoform ratio in the population; and (d) identifying the marker from (b) as a proxy marker for the TL1A isoform ratio if the marker has a statistically significant correlation with the TL1A isoform ratio, wherein optionally the proxy marker relative to a cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition.

9. The method of any one of claims 1 to 7, wherein the proxy marker is identified by the method of claim 8.

10. A computer-implemented method of determining a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”) for a subject, the method comprising: (a) receiving TL1A expression data obtained from a sample from the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition; (b) analyzing the TL1A expression data with a statistical algorithm configured to produce the TL1A isoform ratio; and (d) applying a cutoff to the TL1A isoform ratio, wherein the TL1A isoform ratio relative to the cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition.25743 11. A computer-implemented method of determining a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”) for a subject, the method comprising: (a) obtaining expression data in a sample from the subject; (b) determining expression of TL1A short isoform and TL1A long isoform; (c) calculating the TL1A isoform ratio; and (d) applying a cutoff to the TL1A isoform ratio, wherein the TL1A isoform ratio relative to the cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition.

12. The method of any one of claims 1 to 7 and 9, wherein based on the TL1A isoform ratio is based on TL1A isoform ratio above a cutoff.

13. The method of claim 10 or 11, wherein the TL1A isoform ratio relative to the cutoff is the TL1A isoform ratio above the cutoff.

14. The method of any one of claims 1 to 7 and 9, wherein the proxy marker comprises rs6478109.

15. The method of any one of claims 1 to 7, 9, and 14, wherein based on the proxy marker is (i) based on the proxy marker above a cutoff if the proxy marker and the TL1A isoform ratio has a positive correlation (such proxy marker as “positive proxy marker”); or (ii) based on the proxy marker below a cutoff if the proxy marker and the TL1A isoform ratio has a negative correlation (such proxy marker as “inverse proxy marker”).

16. The method of claim 15, wherein the positive proxy marker is identified by the method of claim 8, wherein the proxy marker and the TL1A isoform ratio has a positive correlation.25743 17. The method of claim 12 to 15, wherein TL1A isoform ratio or a positive proxy marker above a cutoff is determined if an inverse-proxy marker is below an alternative cutoff, wherein the inverse proxy marker has a negative correlation with the TL1A isoform ratio.

18. The method of any one of claims 15 to 17, wherein inverse proxy marker comprises the ratio of TL1A long isoform to the TL1A short isoform.

19. The method of any one of claims 15 to 18, wherein the inverse proxy marker is identified by the method of claim 8, wherein the proxy marker and the TL1A isoform ratio has a negative correlation.

20. The method of any one of claims 12 to 14, wherein TL1A isoform ratio above a cutoff is determined if the ratio of TL1A long isoform to the TL1A short isoform is below an alternative cutoff.

21. The method of any one of claims 10 to 20, wherein the cutoff ranges from about 0.090 to about 0.

110.

22. The method of any one of claims 10 to 21, wherein the cutoff is about 0.

097.

23. The method of claim 21 or 22, wherein the cutoff is for selecting CD patients.

24. The method of any one of claims 10 to 20, wherein the cutoff ranges from about 0.080 to about 0.

10.

25. The method of any one of claims 10 to 20 and 24, wherein the cutoff is about 0.

085.

26. The method of claim 24 or 25, wherein the cutoff is for selecting UC patients.

27. The method of any one of claims 10 to 20, wherein the cutoff is (i) the TL1A isoform ratio or proxy marker level in a heathy subject without the inflammatory, fibrotic, or25743 fibrostenotic disease or condition or (ii) the TL1A isoform ratio or proxy marker level in a tissue not afflicted by the inflammatory, fibrotic, or fibrostenotic disease or condition.

28. The method of any one of claims 1 to 27, wherein the TL1A isoform ratio is calculated as, TL1Ashort / TL1Along, ln(TL1Ashort / TL1Along), or ln(TL1Ashort / TL1Along+n), wherein TL1Ashort is an expression level of the TL1A short isoform, TL1Along is an expression level of the TL1A long isoform, and na positive number.

29. The method of claim 28, wherein n is 1.

30. The method of claim 28 or 29, wherein: (i) the expression level of the TL1A short isoform is the level of gene expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of gene expression of the TL1A long isoform; (ii) the expression level of the TL1A short isoform is the level of protein expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of protein expression of the TL1A long isoform; (iii) the expression level of the TL1A short isoform is the level of gene expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of protein expression of the TL1A long isoform; or (iv) the expression level of the TL1A short isoform is the level of protein expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of gene expression of the TL1A long isoform.

31. The method of any one of claims 1 to 30, wherein the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least about 29%, 30%, 35%, 40%, 45%, 50%, 51%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

32. The method of any one of claims 1 to 31, wherein the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment25743 with the inhibitor of TL1A activity or expression with a specificity of at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

33. The method of any one of claims 1 to 32, wherein the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

34. The method of any one of claims 1 to 33, wherein the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least about 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

35. The method of any one of claims 1 to 34, wherein the TL1A isoform ratio or the proxy marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive rate of at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or 75%.

36. The method of any one of claims 1 to 35, wherein the TL1A isoform ratio or the marker is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

37. The method of any one of claims 10 to 36, wherein the cutoff is such that the TL1A isoform ratio or the proxy marker above the cutoff is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least about 29%, 30%, 35%, 40%, 45%, 50%, 51%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

38. The method of any one of claims 10 to 37, wherein the cutoff is such that the TL1A isoform ratio or the proxy marker above the cutoff is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.25743 39. The method of any one of claims 10 to 38, wherein the cutoff is such that the TL1A isoform ratio or the proxy marker above the cutoff is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a negative predictive value of at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

40. The method of any one of claims 10 to 39, wherein the cutoff is such that the TL1A isoform ratio or the proxy marker above the cutoff is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a sensitivity of at least about 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

41. The method of any one of claims 10 to 40, wherein the cutoff is such that the TL1A isoform ratio or the proxy marker above the cutoff is predictive of an increase of one or more IBD enriched cell types with a positive rate of at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or 75%.

42. The method of any one of claims 10 to 41, wherein the cutoff is such that the TL1A isoform ratio or the proxy marker above the cutoff is predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with an accuracy of at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

43. The method of any one of claims 1 to 42, wherein the TL1A isoform ratio is TL1A isoform ratio in a diseased tissue afflicted by the inflammatory, fibrotic, or fibrostenotic disease or condition.

44. The method of claim 43, wherein the diseased tissue is selected from the group consisting of ileum, colon, rectum, or small intestine.

45. The method of any one of claims 1 to 42, wherein the TL1A isoform ratio is TL1A isoform ratio in a cell contributory to the inflammatory, fibrotic, or fibrostenotic disease or condition.25743 46. The method of claim 45, wherein the cell is selected from the group consisting of a Goblet cell, a pericyte, a smooth muscle cell, an enterocyte, a clonocyte, a monocyte- derived dendritic cells (moDC), a resident macrophage, or a colon transit-amplifying (TA) cell.

47. The method of any one of claims 1 to 42, wherein the TL1A isoform ratio is TL1A isoform ratio in blood of the subject.

48. A computer-implemented system comprising at least one processor and instructions executable by the at least one processor to provide an application configured to determine a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”) for a subject by performing operations comprising: (a) receiving expression data of TL1A short isoform and TL1A long isoform obtained from a sample from the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition; (b) applying an algorithm to the expression data to produce the TL1A isoform ratio; and (d) applying a cutoff to the TL1A isoform ratio, wherein the TL1A isoform ratio relative to the cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression.

49. A computer-implemented system comprising at least one processor and instructions executable by the at least one processor to provide an application configured to determine a ratio between TL1A short isoform and TL1A long isoform (“TL1A isoform ratio”) for a subject by performing operations comprising: (a) receiving expression data of TL1A short isoform and TL1A long isoform obtained from a sample from the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition; and (b) calculating TL1A isoform ratio by utilizing one or more algorithms, wherein the TL1A isoform ratio relative to the cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression.

50. The computer-implemented system of any one of claims 48 to 49, wherein the TL1A isoform ratio relative to the cutoff is the TL1A isoform ratio above the cutoff.25743 51. The computer-implemented system of any one of claims 48 to 50, wherein the cutoff ranges from about 0.090 to 0.

110.

52. The computer-implemented system of any one of claims 48 to 51, wherein the cutoff is about 0.

097.

53. The computer-implemented system of claim 51 and 52, wherein the cutoff is for selecting CD patients.

54. The computer-implemented system of any one of claims 48 to 50, wherein the cutoff ranges from about 0.080 to 0.

10.

55. The computer-implemented system of any one of claims 48 to 50 and 54, wherein the cutoff is about 0.

085.

56. The computer-implemented system of claim 54 and 55, wherein the cutoff is for selecting UC patients.

57. The computer-implemented system of any one of claims 48 to 53, wherein the cutoff is (i) the TL1A isoform ratio or proxy marker level in a heathy subject without the inflammatory, fibrotic, or fibrostenotic disease or condition or (ii) the TL1A isoform ratio or proxy marker level in a tissue not afflicted by the inflammatory, fibrotic, or fibrostenotic disease or condition.

58. The computer-implemented system of any one of claims 48 to 57, wherein the TL1A isoform ratio is calculated as, TL1Ashort / TL1Along, ln(TL1Ashort / TL1Along), or ln(TL1Ashort / TL1Along+n), wherein TL1Ashortis an expression level of the TL1A short isoform, TL1Along is an expression level of the TL1A long isoform, and n is a positive number.

59. The computer-implemented system of claim 58, wherein n is 1.

60. The computer-implemented system of any one of claims 48 to 59, wherein: (i) the expression level of the TL1A short isoform is the level of gene25743 expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of gene expression of the TL1A long isoform; (ii) the expression level of the TL1A short isoform is the level of protein expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of protein expression of the TL1A long isoform; (iii) the expression level of the TL1A short isoform is the level of gene expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of protein expression of the TL1A long isoform; or (iv) the expression level of the TL1A short isoform is the level of protein expression of the TL1A short isoform and the expression level of the TL1A long isoform is the level of gene expression of the TL1A long isoform.

61. The method of any one of claims 1 to 47 or the computer-implemented system of any one of claims 48 to 60, wherein the statistically significant correlation is a correlation with p value less than 0.1, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04.0.03, 0.02, or 0.

01.

62. The method of any one of claims 1 to 47 and 61 or the computer-implemented system of any one of claims 48 to 61, wherein the subject has been treated with an advanced IBD therapy prior to the treatment with the inhibitor of TL1A activity or expression.

63. The method of any one of claims 1 to 47 and 61 to 62 or the computer- implemented system of any one of claims 48 to 62, wherein the subject has not been treated with an advanced IBD therapy prior to the treatment with the inhibitor of TL1A activity or expression.

64. The method or the system of claim 62 or 63, wherein the advanced IBD therapy comprises one or more selected from the group consisting of a biologic therapeutic agent for IBD, an S1P1 modulator, or a JAK inhibitor.

65. The method or the system of claim 64, wherein the biologic therapeutic agent for IBD comprises an anti-71)Į^DQWLERG\^^DQ^DQWL-IL23 antibody, or an anti-integrin Į^ȕ7 antibody.25743 66. The method of any one of claims 1 to 47 and 61 to 65 or the computer- implemented system of any one of claims 48 to 65, wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A (anti-TL1A antibody or antigen binding fragment), wherein the anti-TL1A antibody or antigen binding fragment comprises a heavy chain variable region comprising: (a) an HCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 1; (b) an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 2-5; and (c) an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 6-9; and a light chain variable region comprising: (d) an LCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 10; (e) an LCDR2 comprising an amino acid sequence set forth by SEQ ID NO: 11; and (f) an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 12-15.

67. The method of any one of claims 1 to 47 and 61 to 66 or the computer- implemented system of any one of claims 48 to 66, wherein the inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen binding fragment, wherein the anti-TL1A antibody or antigen binding fragment comprises a heavy chain variable domain comprising an amino acid sequence at least about 90% identical to any one of SEQ ID NOS: 101-135, or 310- 302, and a light chain variable domain comprising an amino acid sequence at least about 90% identical to any one of SEQ ID NOS: 201-206 or 303.

68. The method or system of claim 66 or 67, wherein the heavy chain variable domain comprises an amino acid sequence at least about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 101-135, or 310-302.

69. The method or system of any one of claims 66 to 68, wherein the light chain variable domain comprises an amino acid sequence at least about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 201-206 or 303.

70. The method of any one of claims 1 to 47 and 61 to 69 or the computer- implemented system of any one of claims 48 to 69, wherein the inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen binding fragment, wherein the anti-TL1A antibody or antigen binding fragment comprises: (a) a heavy chain variable framework region comprising a human IGHV1-46*02 framework or a modified human IGHV1-46*02 framework;25743 and (b) a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region collectively comprise less than about 14 amino acid modifications from the human IGHV1-46*02 framework and the human IGKV3-20 framework.

71. The method or system of claim 70, wherein an amino acid modification of the less than 14 amino acid modifications comprises: (a) the amino acid modification is at position 47 in the heavy chain variable region, and the amino acid at position 47 is R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V; (b) the amino acid modification is at position 45 in the heavy chain variable region, and the amino acid at position 45 is A, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V; (c) the amino acid modification is at position 55 in the heavy chain variable region, and the amino acid at position 55 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y, or V; (d) the amino acid modification is at position 78 in the heavy chain variable region, and the amino acid at position 78 is A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, or Y; (e) the amino acid modification is at position 80 in the heavy chain variable region, and the amino acid at position 80 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y, or V; (f) the amino acid modification is at position 82 in the heavy chain variable region, and the amino acid at position 82 is A, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V; (g) the amino acid modification is at position 89 in the heavy chain variable region, and the amino acid at position 89 is A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, or Y; or (h) the amino acid modification is at position 91 in the heavy chain variable region, and the amino acid at position 91 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y, or V; or a combination of two or more modifications selected from (a) to (h).

72. The method or system of claim 71, wherein an amino acid modification of the less than 14 amino acid modifications comprises: A47R, R45K, M55I, V78A, M80I, R82T, V89A, M91L in the heavy chain variable region, per Aho or Kabat numbering.

73. The method or system of claim 71, wherein an amino acid modification of the less than 14 amino acid modifications comprises: (a) a modification at amino acid position 54 in the light chain variable region; and / or (b) a modification at amino acid position 55 in the light chain variable region; per Aho or Kabat numbering.25743 74. The method or system of claim 70, wherein an amino acid modification of the less than 14 amino acid modifications comprises: (a) the amino acid modification is at position 54 of the light chain variable region, and the amino acid at position 54 is A, R, N, D, C, Q, E, G, H, I, K, M, F, P, S, T, W, Y, or V; and / or (b) the amino acid modification is at position 55 of the light chain variable region, and the amino acid at position 55 is A, R, N, D, C, Q, E, G, H, I, K, M, F, P, S, T, W, Y, or V.

75. The method or system of claim 74, wherein an amino acid modification of the less than 14 amino acid modifications comprises L54P and / or L55W in the light chain variable region, per Aho or Kabat numbering.

76. The method of any one of claims 1 to 47 and 61 to 65 or the computer - implemented system of any one of claims 48 to 65, wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A and comprises: a heavy chain variable region comprising SEQ ID NO: 301 X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[HCDR2]RX5 TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR[HCDR3]WGQGTTVTVSS, and a light chain variable region comprising SEQ ID NO: 303 EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11IY[LCDR2]GIPDRFSG SGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V.

77. The method of any one of claims 1 to 47 and 61 to 65 or the computer - implemented system of any one of claims 48 to 65, wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A and comprises: a heavy chain variable region comprising SEQ ID NO: 302 X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[HCDR2]RX5 TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC[HCDR3]WGQGTTVTVSS, and a light chain variable region comprising SEQ ID NO: 303 EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11IY[LCDR2]GIPDRFSG SGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V.25743 78. The method or system of any one of claims76 to 77, wherein: (A)X1 IS Q OR E; (B) X2 IS R OR K (C) X3 IS A OR R; (D)X4 IS M OR I; (E) X5 IS V OR A; (F) X6 IS M OR I; (G)X7 IS R OR T; (H)X8 IS V OR A; (I) X9 IS M OR L (J) X10 IS L OR P; (K)X11 IS L OR W; OR (L) X1-X11 ARE ANY COMBINATION OF (A) TO (K).

79. The method or system of any one of claims 76 to 78, wherein the antibody or antigen binding fragment comprises a heavy chain CDR1 as set forth by SEQ ID NO: 1, a heavy chain CDR2 as set forth by any one of SEQ ID NOS: 2-5, a heavy chain CDR3 as set forth by any one of SEQ ID NOS: 6-9, a light chain CDR1 as set forth by SEQ ID NO: 10, a light chain CDR2 as set forth by SEQ ID NO: 11, and a light chain CDR3 as set forth by any one of SEQ ID NOS: 12-15.

80. The method or system of any one of claims 76 to 78, wherein the antibody or antigen binding fragment comprises a heavy chain framework (FR) 1 as set forth by SEQ ID NO: 304, a heavy chain FR2 as set forth by SEQ ID NO: 305 or SEQ ID NO: 313, a heavy chain FR3 as set forth by any one of SEQ ID NOS: 306, 307, 314, or 315, a heavy chain FR4 as set forth by SEQ ID NO: 308, a light chain FR1 as set forth by SEQ ID NO: 309, a light chain FR2 as set forth by SEQ ID NO: 310, a light chain FR3 as set forth by SEQ ID NO: 311, or a light chain FR4 as set forth by SEQ ID NO: 312, or a combination thereof.

81. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody or antigen binding fragment comprises a human IgG1 Fc region comprising (a) 297A, 297Q, 297G, or 297D, (b) 279F, 279K, or 279L, (c) 228P, (d) 235A, 235E, 235G, 235Q, 235R, or 235S, (e) 237A, 237E,25743 237K, 237N, or 237R, (f) 234A, 234V, or 234F, (g) 233P, (h) 328A, (i) 327Q or 327T, (j) 329A, 329G, 329Y, or 329R (k) 331S, (l) 236F or 236R, (m) 238A, 238E, 238G, 238H, 238I, 238V, 238W, or 238Y, (n) 248A, (o) 254D, 254E, 254G, 254H, 254I, 254N, 254P, 254Q, 254T, or 254V, (p) 255N, (q) 256H, 256K, 256R, or 256V, (r) 264S, (s) 265H, 265K, 265S, 265Y, or 265A, (t) 267G, 267H, 267I, or 267K, (u) 268K, (v) 269N or 269Q, (w) 270A, 270G, 270M, or 270N, (x) 271T, (y) 272N, (z) 292E, 292F, 292G, or 292I, (aa) 293S, (bb) 301W, (cc) 304E, (dd) 311E, 311G, or 311S, (ee) 316F, (ff) 328V, (gg) 330R, (hh) 339E or 339L, (ii) 343I or 343V, (jj) 373A, 373G, or 373S, (kk) 376E, 376W, or 376Y, (ll) 380D, (mm) 382D or 382P, (nn) 385P, (oo) 424H, 424M, or 424V, (pp) 434I, (qq) 438G, (rr) 439E, 439H, or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T, or 440V, (tt) E233P, (uu) L235E, (vv) L234A and L235A, (ww) L234A, L235A, and G237A, (xx) L234A, L235A, and P329G, (yy) L234F, L235E, and P331S, (zz) L234A, L235E, and G237A, (aaa), L234A, L235E, G237A, and P331S (bbb) L234A, L235A, G237A, P238S, H268A, A330S, and P331S (IgG1ı), (ccc) L234A, L235A, and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) any combination of two or more selected from (a) – (uu), per Kabat numbering.

82. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody or antigen binding fragment comprises a human IgG4 Fc region.

83. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody or antigen binding fragment comprises a Fc region comprising a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 320-362.

84. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody of antigen binding fragment comprises a fragment crystallizable (Fc) region comprising reduced antibody- dependent cell-mediated cytotoxicity (ADCC) function as compared to human IgG1 and / or reduced complement-dependent cytotoxicity (CDC) as compared to human IgG1.25743 85. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody or antigen binding fragment comprises a Fc region and wherein the Fc comprises the human IgG1 comprises SEQ ID NO:

320.

86. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody or antigen binding fragment comprises a Fc region and wherein the ADCC function of the Fc region comprising reduced ADCC is at least about 50% reduced as compared to human IgG1.

87. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody or antigen binding fragment comprises a Fc region and wherein the CDC function of the Fc region comprising reduced CDC is at least about 50% reduced as compared to human IgG1.

88. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody or antigen binding fragment comprises a Fc region and wherein the Fc comprises (i) a human IgG4 Fc region or (ii) a human IgG4 Fc region comprising (a) S228P, (b) S228P and L235E, or (c) S228P, F234A, and L235A, per Kabat numbering.

89. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody or antigen binding fragment comprises a Fc region and wherein the Fc comprises a human IgG2 Fc region; IgG2- IgG4 cross-subclass Fc region; IgG2-IgG3 cross-subclass Fc region; IgG2 comprising H268Q, V309L, A330S, P331S (IgG2m4); or IgG2 comprising V234A, G237A, P238S, H268A, V309L, A330S, P331S (IgG2ı^.

90. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody or antigen binding fragment comprises a Fc region and wherein the Fc comprises a human IgG1 with a substitution selected from 329A, 329G, 329Y, 331S, 236F, 236R, 238A, 238E, 238G, 238H, 238I, 238V, 238W, 238Y, 248A, 254D, 254E, 254G, 254H, 254I, 254N, 254P, 254Q, 254T, 254V, 264S,25743 265H, 265K, 265S, 265Y, 265A, 267G, 267H, 267I, 267K, 434I, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T, and 440V, per Kabat numbering.

91. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody or antigen binding fragment comprises a Fc region and wherein the Fc comprises a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 320-362.

92. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody or antigen binding fragment comprises a Fc region and wherein the Fc comprises any one of SEQ ID NOs: 401-413 or a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 401-413.

93. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody or antigen binding fragment comprises a heavy chain comprising any one of SEQ ID NOs: 501-513 or a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 501-513.

94. The method of any one of claims 1 to 47 and 61 to 80 or the computer - implemented system of any one of claims 48 to 80, wherein the antibody or antigen binding fragment comprises a light chain comprising any one of SEQ ID NO: 514 or a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ 515.

95. The method of any one of claims 1 to 47 and 61 to 94 or the computer - implemented system of any one of claims 48 to 94, wherein the inflammatory, fibrotic, or fibrostenotic disease or condition comprises inflammatory bowel disease, Crohn’s disease, obstructive Crohn’s disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, or primary sclerosing cholangitis.25743 96. The method or system of claim 95, wherein the Crohn’s disease is ileal, ileocolonic, or colonic Crohn’s disease.

97. The method of any one of claims 1 to 47 and 61 to 96 or the computer - implemented system of any one of claims 48 to 96, wherein the subject has, or is at risk for developing, a non-response or loss-of-response to a standard therapy comprising glucocorticosteriods, anti-TNF therapy, anti-Į^ȕ7 therapy, anti-IL12p40 therapy, or a combination thereof.

98. The method of any one of claims 28 to 47 and 61 to 97 or the computer - implemented system of any one of claims 48 to 97, wherein expression of the TL1A short isoform and the expression level of the TL1A long isoform is determined by ELISA, RNA sequencing, PCR, or mass spectrometry.

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