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

Daniel Marbach, David Lamparter, Gerald Quon, Manolis Kellis, Zoltán Kutalik, Sven Bergmann

Research output: Contribution to journalArticle

100 Scopus citations

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).

Original languageEnglish (US)
Pages (from-to)366-370
Number of pages5
JournalNature Methods
Volume13
Issue number4
DOIs
StatePublished - Mar 30 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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