A functional genomics predictive network model identifies regulators of inflammatory bowel disease.

Journal Article (Journal Article)

A major challenge in inflammatory bowel disease (IBD) is the integration of diverse IBD data sets to construct predictive models of IBD. We present a predictive model of the immune component of IBD that informs causal relationships among loci previously linked to IBD through genome-wide association studies (GWAS) using functional and regulatory annotations that relate to the cells, tissues, and pathophysiology of IBD. Our model consists of individual networks constructed using molecular data generated from intestinal samples isolated from three populations of patients with IBD at different stages of disease. We performed key driver analysis to identify genes predicted to modulate network regulatory states associated with IBD, prioritizing and prospectively validating 12 of the top key drivers experimentally. This validated key driver set not only introduces new regulators of processes central to IBD but also provides the integrated circuits of genetic, molecular, and clinical traits that can be directly queried to interrogate and refine the regulatory framework defining IBD.

Full Text

Duke Authors

Cited Authors

  • Peters, LA; Perrigoue, J; Mortha, A; Iuga, A; Song, W-M; Neiman, EM; Llewellyn, SR; Di Narzo, A; Kidd, BA; Telesco, SE; Zhao, Y; Stojmirovic, A; Sendecki, J; Shameer, K; Miotto, R; Losic, B; Shah, H; Lee, E; Wang, M; Faith, JJ; Kasarskis, A; Brodmerkel, C; Curran, M; Das, A; Friedman, JR; Fukui, Y; Humphrey, MB; Iritani, BM; Sibinga, N; Tarrant, TK; Argmann, C; Hao, K; Roussos, P; Zhu, J; Zhang, B; Dobrin, R; Mayer, LF; Schadt, EE

Published Date

  • October 2017

Published In

Volume / Issue

  • 49 / 10

Start / End Page

  • 1437 - 1449

PubMed ID

  • 28892060

Pubmed Central ID

  • PMC5660607

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.3947


  • eng

Conference Location

  • United States