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Identification of key genes and pathways associated with Crohn's disease by bioinformatics analysis

By Zheng Wang, Jie Zhu, Lixian Ma

Posted 07 Feb 2019
bioRxiv DOI: 10.1101/543835 (published DOI: 10.1080/00365521.2019.1665096)

Crohn's disease is a type of inflammatory bowel disease posing a significant threat to human health all over the world. Genome-wide gene expression profiles of mucosal colonic biopsies have provided some insight into the molecular mechanisms of Crohn's disease. However, the exact pathogenesis is unclear. This study aimed to identify key genes and significant signaling pathways associated with Crohn's disease by bioinformatics analysis. To identify key genes, an integrated analysis of gene expression signature was conducted using a robust rank aggregation approach. A total of 179 Crohn's disease patients and 94 healthy controls from nine public microarray datasets were included. MMP1 and CLDN8 were two key genes screened from the differentially expressed genes. Connectivity Map predicted several small molecules as possible adjuvant drugs to treat CD. Besides, we used weighted gene co-expression network analysis to explore the co-expression modules associated with Crohn's disease pathogenesis. Seven main functional modules were identified, of which black module showed the highest correlation with Crohn's disease. The genes in black module mainly enriched in Interferon Signaling and defense response to virus. Blue module was another important module and enriched in several signaling pathways, including extracellular matrix organization, inflammatory response and blood vessel development. There were also several other meaningful functional modules which enriched in many biological processes. The present study identified a number of key genes and pathways correlated with Crohn's disease and potential drugs to combat it, which might offer insights into Crohn's disease pathogenesis and provide a clue to potential treatments.

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