@article{f7320e90af814278bcab17d29f50ae4b,
title = "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.",
author = "Peters, {Lauren A.} and Jacqueline Perrigoue and Arthur Mortha and Alina Iuga and Song, {Won Min} and Neiman, {Eric M.} and Llewellyn, {Sean R.} and {Di Narzo}, Antonio and Kidd, {Brian A.} and Telesco, {Shannon E.} and Yongzhong Zhao and Aleksandar Stojmirovic and Jocelyn Sendecki and Khader Shameer and Riccardo Miotto and Bojan Losic and Hardik Shah and Eunjee Lee and Minghui Wang and Faith, {Jeremiah J.} and Andrew Kasarskis and Carrie Brodmerkel and Mark Curran and Anuk Das and Friedman, {Joshua R.} and Yoshinori Fukui and Humphrey, {Mary Beth} and Iritani, {Brian M.} and Nicholas Sibinga and Tarrant, {Teresa K.} and Carmen Argmann and Ke Hao and Panos Roussos and Jun Zhu and Bin Zhang and Radu Dobrin and Mayer, {Lloyd F.} and Schadt, {Eric E.}",
note = "Funding Information: We acknowledge P. Chinnasamy for backcrossing of Aif1−/− mice; E. Esplugues; K. Saulnier from Charles River Laboratories; S. Graham, J. Mena, and G. Lyng from Biomodels; K. Amin from Qiagen; E. Venturini and the New York Genome Center; M. Mahajan, Y. Kasai, and the Genome Core at Mount Sinai; H. Thomas; R. Ng; the Pathology Department and the Histology core at MSH; and Sinai Innovations. This work was supported in part through the computational resources and staff expertise provided by the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai. This work was funded by the Schadt laboratory at the Icahn Institute for Genomics and Multi-scale Biology, Icahn School of Medicine at Mount Sinai (NewYork). This work was partially funded by NIH/NIA grant R01AG046170 (to E.E.S. and B.Z.), a component of the AMP-AD Target Discovery and Preclinical Validation Project, the Rheumatology Research Foundation (to T.K.T.), the Leading Advanced Projects for Medical Innovation (LEAP; to Y.F.) from the Japan Agency for Medical Research and Development (AMED), U01HG008451 (to J.Z.), NIH R01HL128066 (to N.S.), and RO1 AI092093 and R21 AI109020 (to B.M.I.). Publisher Copyright: {\textcopyright} 2017 Nature America, Inc., part of Springer Nature. All rights reserved.",
year = "2017",
month = oct,
day = "1",
doi = "10.1038/ng.3947",
language = "English",
volume = "49",
pages = "1437--1449",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "10",
}