title: Integrative analysis of 111 reference human epigenomes.
abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
authors.affiliation: 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Department of Genetics, Department of Computer Science, 300 Pasteur Dr., Lane Building, L301, Stanford, California 94305-5120, USA.
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authors.affiliation: 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
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authors.lastname: Ernst
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
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authors.lastname: Bilenky
authors.affiliation: 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
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authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
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authors.affiliation: 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
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authors.lastname: Kheradpour
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authors.affiliation: 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
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authors.affiliation: Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, Moores Cancer Center, Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
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authors.affiliation: 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
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authors.affiliation: The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
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authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA.
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authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA.
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authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA.
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authors.affiliation: 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Brigham &Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
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authors.affiliation: Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas, Dallas, NSERL, RL10, 800 W Campbell Road, Richardson, Texas 75080, USA.
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authors.affiliation: Department of Genome Sciences, University of Washington, 3720 15th Ave. NE, Seattle, Washington 98195, USA.
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authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA.
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authors.affiliation: Molecular and Human Genetics Department, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
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authors.affiliation: 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Brigham &Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA. [3] Harvard Medical School, 25 Shattuck St, Boston, Massachusetts 02115, USA.
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authors.affiliation: Department of Biochemistry, Keck School of Medicine, University of Southern California, 1450 Biggy Street, Los Angeles, California 90089-9601, USA.
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authors.affiliation: Center for Biomolecular Sciences and Engineering, University of Santa Cruz, 1156 High Street, Santa Cruz, California 95064, USA.
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authors.forename: Marco A
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authors.affiliation: Department of Microbiology and Immunology, Diabetes Center, University of California, San Francisco, 513 Parnassus Ave, San Francisco, California 94143-0534, USA.
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authors.affiliation: 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Brigham &Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA. [3] Harvard Medical School, 25 Shattuck St, Boston, Massachusetts 02115, USA.
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authors.affiliation: Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0511, USA.
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authors.affiliation: 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, Massachusetts 02139, USA.
authors.forename: Li-Huei
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authors.affiliation: Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, Moores Cancer Center, Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
authors.forename: Wei
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authors.affiliation: USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, Texas 77030, USA.
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authors.affiliation: 1] Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas, Dallas, NSERL, RL10, 800 W Campbell Road, Richardson, Texas 75080, USA. [2] Bioinformatics Division, Center for Synthetic and Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China.
authors.forename: Michael Q
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authors.affiliation: National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, North Carolina 27709, USA.
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authors.affiliation: 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Massachusetts General Hospital, 55 Fruit St, Boston, Massachusetts 02114, USA. [3] Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland 20815-6789, USA.
authors.forename: Bradley E
authors.initials: BE
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authors.affiliation: Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1450 3rd Street, San Francisco, California 94158, USA.
authors.forename: Joseph F
authors.initials: JF
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authors.affiliation: Genomic Analysis Laboratory, Howard Hughes Medical Institute &The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Joseph R
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authors.forename: Martin
authors.initials: M
authors.lastname: Hirst
authors.affiliation: 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Department of Stem Cell and Regenerative Biology, 7 Divinity Ave, Cambridge, Massachusetts 02138, USA.
authors.forename: Alexander
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authors.affiliation: Epigenome Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Milosavljevic
authors.affiliation: 1] Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, Moores Cancer Center, Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. [2] Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093, USA.
authors.forename: Bing
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authors.lastname: Ren
authors.affiliation: Department of Genome Sciences, University of Washington, 3720 15th Ave. NE, Seattle, Washington 98195, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Stamatoyannopoulos
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA.
authors.forename: Ting
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authors.lastname: Wang
authors.affiliation: 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
authors.forename: Manolis
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mesh_terms: D001483:Base Sequence; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002877:Chromosomes, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D066264:Datasets as Topic; D004742:Enhancer Elements, Genetic / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D057890:Epigenomics; D014644:Genetic Variation / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study; D006657:Histones / Q000378:metabolism; D006801:Humans; D009928:Organ Specificity / Q000235:genetics; D012313:RNA / Q000235:genetics; D012016:Reference Values
chemical_list: D002843:Chromatin; D006657:Histones; D012313:RNA; D004247:DNA