Reference-guided genome assembly of long non-coding rna transcripts reveals target genes associated with Crohn’s disease
Year: 2026
Type: article
Abstract: Crohn's disease (CD) is highly heterogeneous in presentation and progression with no cure. Molecular phenotyping has been used to elucidate cellular and tissue-based alterations to characterize drivers and effects of disease. One currently understudied class of functional molecules is long non-coding RNAs (lncRNAs). Studying the full lncRNA landscape in CD is challenging due in part to an incomplete lncRNA annotation and a lack of their functional characterization in tissues of interest. We used a genome-guided alignment strategy to assemble predicted lncRNA transcripts using short RNA-sequencing data from colon tissue of adult patient samples. When combining our predicted lncRNAs with previous lncRNA annotations, we determined 98 that were differentially expressed, recapitulating many from previous IBD studies while also uncovering new ones. We built gene co-expression networks to cluster lncRNAs with functionally characterized protein-coding genes. Clusters containing differential lncRNAs were correlated to disease status and associated with pathways related to the humoral immune response, metabolism, and tissue regeneration. We uncovered multiple differential lncRNAs whose expression significantly correlated with nearby differential protein-coding genes that have also been differentially expressed in other IBD datasets, such as PITX2. We focused on a predicted lncRNA that is antisense to the PITX2-adjacent lncRNA PANCR, which we called PANCR-AS1, and provide multiple lines of evidence that support PANCR-AS1 functioning as an enhancer of PITX2 expression. Overall, we determined lncRNAs that are potential contributors to CD pathogenesis. We developed a robust pipeline for identifying lncRNAs in diseased and non-diseased tissue that are absent from reference annotations. We also outlined a framework to pinpoint significant disease-associated lncRNAs with potential functional activity related to their nearby protein-coding genes.
Source: Scientific Reports
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: G3126295069, Enhancement Training for the Next Generation of Translational Ph.D. Scientists, Identifying Microbial, Epithelial and Immune Cell Interactions that Mediate Mucosal Homeostasis and Determine IBD Phenotypes, Multi-omic characterization of genetic variants in IBD risk loci, G8311213688, Using molecular quantitative trait loci mapping approaches to determine candidate gene regulatory mechanisms of functional variants within inflammatory bowel disease GWAS loci., Predoctoral Training Program in Bioinformatics and Computational Biology, Center for Gastrointestinal Biology and Disease, High throughput functional studies of IBD-associated GWAS variants
OpenAlex ID: W4414742006