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Nat Methods. 2016 Apr;13(4):366-70. doi: 10.1038/nmeth.3799. Epub 2016 Mar 7.

Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases.

Author information

1
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
2
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
3
Broad Institute, MIT, Cambridge, Massachusetts, USA.
4
Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, Massachusetts, USA.
5
Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, Switzerland.

Abstract

Mapping perturbed molecular circuits that underlie complex diseases remains a great challenge. We developed a comprehensive resource of 394 cell type- and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity among transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) showed that disease-associated genetic variants--including variants that do not reach genome-wide significance--often perturb regulatory modules that are highly specific to disease-relevant cell types or tissues. Our resource opens the door to systematic analysis of regulatory programs across hundreds of human cell types and tissues (http://regulatorycircuits.org).

PMID:
26950747
PMCID:
PMC4967716
DOI:
10.1038/nmeth.3799
[Indexed for MEDLINE]
Free PMC Article

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