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

First Author  Peters LA Year  2017
Journal  Nat Genet Volume  49
Issue  10 Pages  1437-1449
PubMed ID  28892060 Mgi Jnum  J:259912
Mgi Id  MGI:6140337 Doi  10.1038/ng.3947
Citation  Peters LA, et al. (2017) A functional genomics predictive network model identifies regulators of inflammatory bowel disease. Nat Genet 49(10):1437-1449
abstractText  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.
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