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Reference-guided Genome Assembly of Long Non-coding RNA Transcripts Reveals Target Genes Associated With Crohn's

Meaghan M Kennedy Ng^1,2, Sophie Silverstein³, Nina C Nishiyama^1,2

¹Curriculum in Bioinformatics and Computational Biology, Department of Genetics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Biorxiv : the Preprint Server for Biology

|November 19, 2025

Summary

This summary is machine-generated.

Researchers identified novel long non-coding RNAs (lncRNAs) in Crohn's disease (CD) colon tissue, revealing their potential roles in immune response and metabolism. A new pipeline aids in discovering these crucial molecules for understanding CD pathogenesis.

Keywords:

Crohn’s disease long non-coding RNAs transcriptomics

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Area of Science:

Genomics
Molecular Biology
Gastroenterology

Background:

Crohn's disease (CD) is a heterogeneous inflammatory bowel disease (IBD) with no cure.
Long non-coding RNAs (lncRNAs) are understudied in IBD pathogenesis.
Challenges exist in lncRNA annotation and functional characterization in relevant tissues.

Purpose of the Study:

To identify and characterize novel lncRNAs in colon tissue from CD patients.
To explore the functional roles of lncRNAs in CD pathogenesis.
To develop a pipeline for lncRNA discovery in IBD.

Main Methods:

Genome-guided alignment of short RNA-sequencing data to assemble predicted lncRNA transcripts.
Integration of predicted lncRNAs with existing annotations to identify differentially expressed lncRNAs.
Gene co-expression network construction to cluster lncRNAs with protein-coding genes.
Correlation analysis of lncRNA expression with disease status and pathways.

Main Results:

Identified 98 differentially expressed lncRNAs, including novel candidates, in CD colon tissue.
Discovered lncRNA clusters associated with immune response, metabolism, and tissue regeneration pathways.
Found correlations between differential lncRNAs and nearby protein-coding genes, such as PITX2.
Provided evidence for a novel lncRNA, PANCR-AS1, enhancing PITX2 expression.

Conclusions:

lncRNAs are potential contributors to Crohn's disease pathogenesis.
A robust pipeline was developed for identifying novel lncRNAs in diseased tissues.
A framework was established to pinpoint disease-associated lncRNAs with functional relevance to nearby genes.