Daniel Groso, a senior biology major at the University of Florida, applied a computational method to map spatial patterns of gene expression in the diseased gut tissue context.
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. The cellular makeup in the tissue context of inflammation and resolution of inflammation, particularly differences between healthy and inflamed sections of the gut, remain unclear. A better understanding of gene expression patterns in different states of inflammation may help to better characterize IBD heterogeneity, and computational approaches for analysis of spatial transcriptomic data can be utilized to precisely map cell types that are drivers of IBD.
BSRP was an eye-opening and incredibly memorable experience. I was excited to find my niche within the Broad’s dynamic research and cultural environment. The network I’ve interacted with during BSRP, from my cohort members to scientific leaders of many disciplines, continues to inspire me. I am incredibly grateful for the opportunity and am indebted to the wonderful people who made this experience possible.
We obtained tissue samples from IBD patients, processed these samples with the 10x Genomics Visium platform, and used the computational tool BayesSpace to uncover biologically relevant spatial domains. Using BayesSpace’s enhancement algorithm, we further refined the resolution of these clusters to the subspot (near-single-cell) level. This enhanced spatial information was then used to map out expression of a variety of marker genes that may play a role in inflammation.
We found that several genes are differentially expressed in inflamed tissue, including markers for naive immune cells, fibroblasts, and neuroendocrine cells. In addition, we elucidated 17 spatial clusters that are shared across samples and investigated their distribution in healthy and diseased states. Our analyses yield novel insight into differentially expressed genes in inflamed gut tissue samples. This information may help point to signaling pathways for targeted treatment of IBD and provide additional insight into the molecular processes that are characteristic of disease in the tissue context.
Project: Spatially Resolved Expression Patterns of the Diseased Gastrointestinal Tract
Mentors: Sathish Subramanian, Ramnik Xavier, Xavier Lab