Isoform-resolved transcriptome in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is a group of chronic diseases that cause inflammation in the intestines, including ulcerative colitis (UC) and Crohn's disease (CD). Numerous omics studies have been published to understand IBD pathogenesis and identify potential targets for therapeutics. Despite the high amount RNA-seq data from short reads sequencing platforms produced to help preclinical and clinical research in IBD, such studies fail to capture the full-length mRNAs and various isoforms from alternative splicing events. Thus, the transcriptome associated with IBD has been understudied. The IsoSeq system of PacBio Sequel platforms enables sequence large number of long transcripts, and the corresponding IsoSeq pipeline and additional bioinformatics tools can identify the full-length transcripts and various isoforms. Here, we generate isoform-resolved transcriptome in IBD patients by performing long-read RNA sequencing on samples from four IBD patients and two healthy controls and integrate the full-length transcripts data with short-read RNA sequencing data from 99 IBD patients and controls. We identify numerous unannotated isoforms transcribed from both known and unannotated genes. Our bioinformatics pipeline further identified sQTL by integrating variants predicted from RNAseq with the isoforms from IsoSeq. We also identified isoform switch associated with IBD, and genes correlated with isoforms. Further pathway analysis and gene annotation search were conducted to understand the IBD disease. Together, our findings show that the transcriptome associated with IBD is far more complex than currently known, and our results will act as a valuable resource to empower future studies for IBD.