title: Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases.
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).
authors.affiliation: Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.|Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Marbach
authors.affiliation: Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.|Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Lamparter
authors.affiliation: Broad Institute, MIT, Cambridge, Massachusetts, USA.|Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, Massachusetts, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Quon
authors.affiliation: Broad Institute, MIT, Cambridge, Massachusetts, USA.|Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, Massachusetts, USA.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.affiliation: Swiss Institute of Bioinformatics, Lausanne, Switzerland.|Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Zoltán
authors.identifier: http://orcid.org/0000-0001-8285-7523
authors.initials: Z
authors.lastname: Kutalik
authors.affiliation: Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.|Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Sven
authors.initials: S
authors.lastname: Bergmann
mesh_terms: D001927:Brain Diseases / Q000235:genetics* / Q000378:metabolism*; D019070:Cell Lineage / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D057890:Epigenomics; D053263:Gene Regulatory Networks; D014644:Genetic Variation / Q000235:genetics; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D025941:Protein Interaction Mapping / Q000379:methods; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014157:Transcription Factors