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In partial fulfillment of the requirements for the degree of
Doctor of Philosophy in Bioinformatics
in the School of Biological Sciences
Angela Mo
Defends her thesis:
Genomic and Transcriptomic Characterization of Inflammatory Bowel Disease
Friday, April 2, 2021
2:00 PM Eastern Time
https://bluejeans.com/771161957
Thesis Advisor:
Dr. Greg Gibson
School of Biological Sciences
Georgia Institute of Technology
Committee Members:
Dr. Joseph Lachance
School of Biological Sciences
Georgia Institute of Technology
Dr. I. King Jordan
School of Biological Sciences
Georgia Institute of Technology
Dr. Peng Qiu
Department of Biomedical Engineering
Georgia Institute of Technology
Dr. Subra Kugathasan
Department of Pediatrics and Human Genetics
Emory University
Abstract
Inflammatory bowel disease (IBD) is a chronic idiopathic disorder resulting in the inflammation of the gastrointestinal tract, which encapsulates both Crohn’s disease (CD) and ulcerative colitis (UC). There is strong evidence of familial aggregation of IBD, and more than 200 genetic variants have been identified as associated with IBD . Currently, more than 1.5 million individuals in the United States suffer from IBD, with prevalence of the disease on the rise, particularly in minority populations. The primary question driving this thesis is whether genomic and transcriptomic profiling have the potential to direct personalized therapeutic interventions for IBD patients. Prediction of disease course is especially relevant in IBD, because early, appropriate introduction of anti-TNFα therapy can slow the progression of the disease in patients who would otherwise experience severe flares, bowel penetration, or require invasive surgeries. Conversely, early prediction can also identify patients who are not expected to progress and thus help to avoid unnecessary, harmful, and costly therapy with biologics. Our prior studies have demonstrated that transcriptomic data can be used to identify patients who are likely to progress from B1 stable CD to B3 penetrating CD, and that gene expression can also be linked to GWAS via Transcriptional Risk Scores (TRS).
In this thesis, I first describe a comparative analysis of gene expression and eQTL in IBD and juvenile idiopathic arthritis, another clinically heterogeneous immune-related disorder. Next, I examine the influence of African ancestry proportion on gene expression in the ileum of Crohn’s disease patients. I then discuss the utility of gene expression at time of disease diagnosis to predict risk of progression to colectomy in an inception cohort of pediatric ulcerative colitis patients. Finally, I present an exploration of cell type composition of ileal epithelial cells at single-cell resolution in healthy, treatment-naïve, and treated Crohn’s disease. I conclude with a summary of the progress achieved and challenges to be overcome for the successful application of genomics for precision medicine in IBD and beyond.
