文章基本信息

标题：Computational drug repurposing for inflammatory bowel disease using genetic information
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作者：Liam Grenier ; Pingzhao Hu
期刊名称：Computational and Structural Biotechnology Journal
印刷版ISSN：2001-0370
出版年度：2019
卷号：17
页码：127-135
DOI：10.1016/j.csbj.2019.01.001
出版社：Computational and Structural Biotechnology Journal
摘要：As knowledge of the genetics behind inflammatory bowel disease (IBD) has continually improved, there has been a demand for methods that can use this data in a clinically significant way. Genome-wide association analyses for IBD have identified 232 risk genetic loci for the disorder. While identification of these risk loci enriches our understanding of the underlying biology of the disorder, their identification does not serve a clinical purpose. A potential use of this genetic information is to look for potential IBD drugs that target these loci in a procedure known as drug repurposing. The demand for new drug treatments for IBD is high due to the side effects and high costs of current treatments. We hypothesize that IBD genetic variants obtained from GWAS and the candidate genes prioritized from the variants have a causal relationship with IBD drug targets. A computational drug repositioning study was done due to its efficiency and inexpensiveness compared to traditional in vitro or biochemical approaches. Our approach for drug repurposing was multi-layered; it not only focused on the interactions between drugs and risk IBD genes, but also the interactions between drugs and all of the biological pathways the risk genes are involved in. We prioritized IBD candidate genes using identified genetic variants and identified potential drug targets and drugs that can be potentially repositioned or developed for IBD using the identified candidate genes. Our analysis strategy can be applied to repurpose drugs for other complex diseases using their risk genes identified from genetic analysis.
关键词：Inflammatory bowel disease ; Risk genes ; Drug repurposing ; Computational approach ; Pathway enrichment