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Potential IBD Methylation, Expression Markers Presented at BoG

COLD SPRING HARBOR, NY (GenomeWeb) – Researchers from the UK and Germany have identified gene expression and DNA methylation profiles that appear to distinguish between intestinal epithelial samples from children with or without inflammatory bowel disease (IBD), attendees heard at the Biology of Genomes meeting last night.

Kate Howell, a pediatrics and statistical genomics researcher affiliated with the University of Cambridge and the European Bioinformatics Institute, presented findings from a multi-'omics study of a few dozen pediatric IBD cases during a session on computational genomics.

She and her colleagues used a combination of genotyping, RNA sequencing, genome-wide DNA methylation profiling, and gut microbial community membership analyses to assess purified intestinal epithelial samples isolated from the large colon and ileum of the small intestine in about 40 children with Crohn's disease or ulcerative colitis and matched healthy control individuals.

While DNA methylation patterns consistently differed depending on the original sites of the biopsy samples, the team saw similar methylation patterns at each gut site regardless of whether children had Crohn's disease or ulcerative colitis.

The group's subsequent modeling analyses indicated that the combination of RNA-sequencing and genome-wide methylation data distinguished IBD from control cases with better resolution than the IBD risk variants, microbiome, expression, or methylation data alone. They also noted that DNA methylation patterns at diagnosis seemed to contain clues to disease severity.

Though Crohn's disease and ulcerative colitis are both marked by chronic, relapsing inflammation of the gut, Howell explained, the IBD conditions differ somewhat with respect to the gut region affected and the type of inflammation detected by colonoscopy. And while the conditions are known to have genetic contributors, IBD cases have been on the rise over the past few decades, she noted, highlighting the potential importance of non-genetic risk factors.

In an effort to complement past studies of the conditions — which run the gamut from genome-wide association searches for IBD-associated variants to microbiome sequencing studies pointing to decreased microbial diversity in the guts of IBD-affected individuals — the team focused on intestinal epithelial cells, reasoning that the cell type's role in gut function and immunity might offer particularly relevant insights into IBD pathogenesis.

Generally speaking, expression and methylation patterns often overlapped between children with Crohn's disease and ulcerative colitis when samples from the same part of the intestine were considered. On the other hand, both methylation and gene expression profiles differed depending on the site sampled, Howell explained. For example, biopsy samples collected from the ileum of children with IBD tended to show expression shifts involving components of signal transduction pathways, while immune response gene expression changes were more common in the colon.

Based on the preliminary success they've had using gene expression and DNA methylation to come up with a potential diagnostic model for IBD, the team hopes to expand its analyses to larger pediatric IBD cohorts with more biopsy samples per individual in the hopes of further improving its model and uncovering clues to other IBD features, including disease-specific biology and treatment outcomes.