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

Abstract：

: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.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Peters LA,Perrigoue J,Mortha A,Iuga A,Song WM,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

doi

10.1038/ng.3947

subject

Has Abstract

pub_date

2017-10-01 00:00:00

pages

1437-1449

issue

10

eissn

1061-4036

issn

1546-1718

pii

ng.3947

journal_volume

49

pub_type

杂志文章

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