What question did this study set out to answer?

This research aims to develop a transcriptomic signature indicating disease severity in ulcerative colitis and validate its clinical relevance.

January 23, 2026

DOP054Identification of a Molecular Signature of Disease Severity in Ulcerative Colitis Using a Systems Biology Approach and Clinical Impact Using VARSITY Trial Data

Key Points

This research aims to develop a transcriptomic signature indicating disease severity in ulcerative colitis and validate its clinical relevance.
Developed a molecular disease activity score using transcriptomics data from ulcerative colitis samples.
Employed elastic net regression for modeling expression data against disease activity scores.
Analyzed data from mucosal biopsies collected from multiple ulcerative colitis studies.
Compared gene signatures with those from the VARSITY trial to validate findings.
Identified an 85-gene signature linked to diverse cellular populations in ulcerative colitis.
The molecular signature showed significant correlation with clinical assessment scores across IBD cohorts.
Validation in VARSITY data indicated strong ties between the gene signature and patient therapy responses.

Abstract

Abstract Background We aimed to develop and validate a transcriptomic signature that correlates with clinical disease activity and therapy response using the Inflammatory Bowel Disease (IBD) Plexus® real-world data platform (Crohn’s 381(13):1215-1226. 2.Zou H, et al. Regularization and Variable Selection Via the Elastic Net. J R Stat Soc Series B Stat Methodol. 2005;67(2):301-320. 3.Argmann C, et al. Biopsy and blood-based molecular biomarker of inflammation in IBD. Gut. 2023;72(7):1271-1287. 4.Friedrich, M. et al. IL-1-driven stromal-neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies. Nat Med. 2021;27(11):1970-1981. Conflict of interest: Dulai, Parambir: Grant:Takeda, Bristol Meyer Squibb, Merck, Genentech, Geneoscopy. Personal Fees: Abbvie, Abivax, Alimentiv, Bristol Meyer Squibb, Boehringer Ingelheim, Celltrion, Cristcot, Genentech, Geneoscopy, Janssen, Lilly, Merck, Pfizer, Sanofi, Takeda. Panchal, Pratik: Employee of Takeda and holds stock/options in Takeda. Tang, Jay: Employee of Takeda and holds stock/options in Takeda. Wennbo, Haakan: Takeda employee Agboton, Christian: Employee of Takeda and holds stock/options in Takeda. Romo Bautista, Itzel: Employee of Takeda and holds stock/options in Takeda. Cogan, Adi: Employee and shareholder of CytoReason, which has received research funding from Takeda. Wyrobnik, Iris: Employee and shareholder of CytoReason, which has received research funding from Takeda. Farahmand, Saman: Employee of Takeda and holds stock/options in Takeda. Paraskevopoulou, Maria: Other: Maria Paraskevopoulou is employee and shareholder of Takeda Schuster, Ronen: Employee and shareholder of CytoReason, which has received research funding from Takeda. Sirota-Madi, Alexandra: Employee and shareholder of CytoReason, which has received research funding from Takeda. Shen-Orr, Shai: Consultant for and shareholder of CytoReason Chowers, Yehuda: Employee and shareholder of CytoReason, which has received research funding from Takeda. Arunachalam, Vinayagam: Employee of Takeda and holds stock/options in Takeda.

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