Prioritisation and Network Analysis of Crohn's Disease Susceptibility Genes

Abstract

Recent Genome-Wide Association Studies (GWAS) have revealed numerous Crohn's disease susceptibility genes and a key challenge now is in understanding how risk polymorphisms in associated genes might contribute to development of this disease. For a gene to contribute to disease phenotype, its risk variant will likely adversely communicate with a variety of other gene products to result in dysregulation of common signaling pathways. A vital challenge is to elucidate pathways of potentially greatest influence on pathological behaviour, in a manner recognizing how multiple relevant genes may yield integrative effect. In this work we apply mathematical analysis of networks involving the list of recently described Crohn's susceptibility genes, to prioritise pathways in relation to their potential development of this disease. Prioritisation was performed by applying a text mining and a diffusion based method (GRAIL, GPEC). Prospective biological significance of the resulting prioritised list of proteins is highlighted by changes in their gene expression levels in Crohn's patients intestinal tissue in comparison with healthy donors.

A Review of Recent Advancement in Integrating Omics Data with Literature Mining towards Biomedical Discoveries

“…Genome-Wide Association Study (GWAS), also known as Whole Genome Association Study (WGAS), is a relatively new approach for identifying genes (i.e., loci associated with human traits) through rapid scanning of markers across whole DNA or genome [ 70 ]. GWAS has been applied also to cancer research for drug repositioning [ 71 ], prioritizing susceptible genes in Crohn's disease [ 72 ], and analyzing the human variants in the area of precision medicine [ 73 ]. As an example, the Michigan Genomics Initiatives (MGI) at the University of Michigan has developed an institutional based DNA and genetics repository combined with patient phenotype.…”

Systems pharmacology and molecular docking strategies prioritize natural molecules as cardioprotective agents

“…The Benjamini and Hochberg false discovery rate method was selected by default to adjust P-values for multiple testing. 38 In this study, we selected the top 250 differentially expressed genes and submit the upregulated 39 First, a microarray study of accession number GSE8051 (ref. 40) was conducted for discovering the gene expression in resistance artery of hypertension rat models and we reanalyzed the differential expression between male Wistar-Kyoto (WKY) and age-matched spontaneously hypertensive rats.…”