Transcriptome-wide Differential Expression and Splicing in Inflammatory Bowel Disease Patients
- 1Curriculum in Bioinformatics and Computational Biology, Department of Genetics, School of Medicine, Department of Biology, College of Arts and Sciences, The Uni
Abstract
The inflammatory bowel diseases (IBD), comprising mainly Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic intestinal inflammation driven in part by complex genetic and gene regulatory mechanisms. Although transcriptomic studies have defined broad expression changes in IBD, the contribution of alternative splicing to disease-associated molecular variation remains less clear. We therefore integrated differential expression (DE) and differential splicing (DS) analyses in macroscopically uninvolved colonic mucosal biopsies from patients with either CD or UC along with non-IBD controls to define gene expression and intron-usage changes across disease subtypes. We identified 491 DS and 316 DE genes in CD vs. non-IBD, and 1,298 DS and 1,107 DE genes in UC vs. non-IBD. DS and DE genes were nearly mutually exclusive, with no overlapping genes in CD and 16 in UC. Consistent with this result, pathway analysis showed that differentially expressed and differentially spliced genes were associated with related but distinct biological programs. DE genes were involved in chromatin organization, transcriptional regulation, and metabolic pathways for glycans and drugs, whereas DS genes were enriched for splicing, cellular signaling, and lipid metabolism. We found substantial similarity in enriched pathways across CD and UC with some notable exceptions, including increased enrichment of DS and DE genes involved in extracellular vesicles and exosomes in CD and enrichment of DS genes in ER-to-Golgi trafficking and stress granules in UC. Direct comparisons of CD and UC patients additionally show differential splicing usage in genes involved in cell adhesion pathways. These findings identify alternative splicing as a major contributor to transcriptomic changes in IBD that is largely distinct from changes in expression level and provide a broader view of molecular contributors to IBD.
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BibTeX
@misc{han2026transcriptomewide,
title = {{Transcriptome-wide Differential Expression and Splicing in Inflammatory Bowel Disease Patients}},
author = {S. Han and Y.-C. Huang and S. Silverstein and M. Bauer and M. R. Kapadia and G. Lau and G. Lian and R. Rahbar and T. S. Sadiq and M. R. Schaner and J. Stem and D. Weaver and B. Huan and A. LaCorte and S. Z. Sheikh and T. S. Furey},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.24.759415},
url = {https://www.biorxiv.org/content/10.64898/2026.10.24.759415v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Transcriptome-wide Differential Expression and Splicing in Inflammatory Bowel Disease Patients
AU - S. Han
AU - Y.-C. Huang
AU - S. Silverstein
AU - M. Bauer
AU - M. R. Kapadia
AU - G. Lau
AU - G. Lian
AU - R. Rahbar
AU - T. S. Sadiq
AU - M. R. Schaner
AU - J. Stem
AU - D. Weaver
AU - B. Huan
AU - A. LaCorte
AU - S. Z. Sheikh
AU - T. S. Furey
PY - 2026
DA - 2026/10/24
PB - bioRxiv
DO - 10.64898/2026.10.24.759415
UR - https://www.biorxiv.org/content/10.64898/2026.10.24.759415v1
AB - The inflammatory bowel diseases (IBD), comprising mainly Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic intestinal inflammation driven in part by complex genetic and gene regulatory mechanisms. Although transcriptomic studies have defined broad expression changes in IBD, the contribution of alternative splicing to disease-associated molecular variation remains less clear. We therefore integrated differential expression (DE) and differential splicing (DS) analyses in macroscopically uninvolved colonic mucosal biopsies from patients with either CD or UC along with non-IBD controls to define gene expression and intron-usage changes across disease subtypes. We identified 491 DS and 316 DE genes in CD vs. non-IBD, and 1,298 DS and 1,107 DE genes in UC vs. non-IBD. DS and DE genes were nearly mutually exclusive, with no overlapping genes in CD and 16 in UC. Consistent with this result, pathway analysis showed that differentially expressed and differentially spliced genes were associated with related but distinct biological programs. DE genes were involved in chromatin organization, transcriptional regulation, and metabolic pathways for glycans and drugs, whereas DS genes were enriched for splicing, cellular signaling, and lipid metabolism. We found substantial similarity in enriched pathways across CD and UC with some notable exceptions, including increased enrichment of DS and DE genes involved in extracellular vesicles and exosomes in CD and enrichment of DS genes in ER-to-Golgi trafficking and stress granules in UC. Direct comparisons of CD and UC patients additionally show differential splicing usage in genes involved in cell adhesion pathways. These findings identify alternative splicing as a major contributor to transcriptomic changes in IBD that is largely distinct from changes in expression level and provide a broader view of molecular contributors to IBD.
ER -