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Integrative analysis of 111 reference human epigenomes

Author

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  • Anshul Kundaje

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
    300 Pasteur Dr., Lane Building, L301, Stanford, California 94305-5120, USA.)

  • Wouter Meuleman

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Jason Ernst

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
    University of California, Los Angeles, 615 Charles E Young Dr South, Los Angeles, California 90095, USA.)

  • Misha Bilenky

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.)

  • Angela Yen

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Alireza Heravi-Moussavi

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.)

  • Pouya Kheradpour

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Zhizhuo Zhang

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Jianrong Wang

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Michael J. Ziller

    (The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
    7 Divinity Ave, Cambridge, Massachusetts 02138, USA.)

  • Viren Amin

    (Epigenome Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.)

  • John W. Whitaker

    (Institute of Genomic Medicine, Moores Cancer Center, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.)

  • Matthew D. Schultz

    (Genomic Analysis Laboratory, Howard Hughes Medical Institute & The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA.)

  • Lucas D. Ward

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Abhishek Sarkar

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Gerald Quon

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Richard S. Sandstrom

    (University of Washington, 3720 15th Ave. NE, Seattle, Washington 98195, USA.)

  • Matthew L. Eaton

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Yi-Chieh Wu

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Andreas R. Pfenning

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Xinchen Wang

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
    Massachusetts Institute of Technology, 31 Ames St, Cambridge, Massachusetts 02142, USA.)

  • Melina Claussnitzer

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Yaping Liu

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Cristian Coarfa

    (Epigenome Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.)

  • R. Alan Harris

    (Epigenome Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.)

  • Noam Shoresh

    (The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Charles B. Epstein

    (The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Elizabeta Gjoneska

    (The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
    The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, Massachusetts 02139, USA.)

  • Danny Leung

    (Institute of Genomic Medicine, Moores Cancer Center, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093, USA.)

  • Wei Xie

    (Institute of Genomic Medicine, Moores Cancer Center, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093, USA.)

  • R. David Hawkins

    (Institute of Genomic Medicine, Moores Cancer Center, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093, USA.)

  • Ryan Lister

    (Genomic Analysis Laboratory, Howard Hughes Medical Institute & The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA.)

  • Chibo Hong

    (Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1450 3rd Street, San Francisco, California 94158, USA.)

  • Philippe Gascard

    (University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0511, USA.)

  • Andrew J. Mungall

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.)

  • Richard Moore

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.)

  • Eric Chuah

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.)

  • Angela Tam

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.)

  • Theresa K. Canfield

    (University of Washington, 3720 15th Ave. NE, Seattle, Washington 98195, USA.)

  • R. Scott Hansen

    (University of Washington, 2211 Elliot Avenue, Seattle, Washington 98121, USA.)

  • Rajinder Kaul

    (University of Washington, 2211 Elliot Avenue, Seattle, Washington 98121, USA.)

  • Peter J. Sabo

    (University of Washington, 3720 15th Ave. NE, Seattle, Washington 98195, USA.)

  • Mukul S. Bansal

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
    University of Connecticut, 371 Fairfield Way, Storrs, Connecticut 06269, USA.)

  • Annaick Carles

    (University of British Columbia, 2125 East Mall, Vancouver, British Columbia V6T 1Z4, Canada.)

  • Jesse R. Dixon

    (Institute of Genomic Medicine, Moores Cancer Center, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093, USA.)

  • Kai-How Farh

    (The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Soheil Feizi

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Rosa Karlic

    (Bioinformatics Group, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia.)

  • Ah-Ram Kim

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Ashwinikumar Kulkarni

    (Center for Systems Biology, The University of Texas, Dallas, NSERL, RL10, 800 W Campbell Road, Richardson, Texas 75080, USA.)

  • Daofeng Li

    (Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA.)

  • Rebecca Lowdon

    (Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA.)

  • GiNell Elliott

    (Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA.)

  • Tim R. Mercer

    (Institute for Molecular Bioscience, University of Queensland)

  • Shane J. Neph

    (University of Washington, 3720 15th Ave. NE, Seattle, Washington 98195, USA.)

  • Vitor Onuchic

    (Epigenome Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.)

  • Paz Polak

    (The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
    Brigham & Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.)

  • Nisha Rajagopal

    (Institute of Genomic Medicine, Moores Cancer Center, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093, USA.)

  • Pradipta Ray

    (Center for Systems Biology, The University of Texas, Dallas, NSERL, RL10, 800 W Campbell Road, Richardson, Texas 75080, USA.)

  • Richard C. Sallari

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Kyle T. Siebenthall

    (University of Washington, 3720 15th Ave. NE, Seattle, Washington 98195, USA.)

  • Nicholas A. Sinnott-Armstrong

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

  • Michael Stevens

    (Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA.
    Washington University in St. Louis)

  • Robert E. Thurman

    (University of Washington, 3720 15th Ave. NE, Seattle, Washington 98195, USA.)

  • Jie Wu

    (Stony Brook University
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.)

  • Bo Zhang

    (Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA.)

  • Xin Zhou

    (Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA.)

  • Arthur E. Beaudet

    (Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.)

  • Laurie A. Boyer

    (Massachusetts Institute of Technology, 31 Ames St, Cambridge, Massachusetts 02142, USA.)

  • Philip L. De Jager

    (The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
    Brigham & Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
    Harvard Medical School, 25 Shattuck St, Boston, Massachusetts 02115, USA.)

  • Peggy J. Farnham

    (Keck School of Medicine, University of Southern California, 1450 Biggy Street, Los Angeles, California 90089-9601, USA.)

  • Susan J. Fisher

    (ObGyn, Reproductive Sciences, University of California San Francisco, 35 Medical Center Way, San Francisco, California 94143, USA.)

  • David Haussler

    (Center for Biomolecular Sciences and Engineering, University of Santa Cruz, 1156 High Street, Santa Cruz, California 95064, USA.)

  • Steven J. M. Jones

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
    Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada.
    University of British Columbia, 2329 West Mall, Vancouver, BC, Canada, V6T 1Z4.)

  • Wei Li

    (Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.)

  • Marco A. Marra

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
    University of British Columbia, 2329 West Mall, Vancouver, BC, Canada, V6T 1Z4.)

  • Michael T. McManus

    (Diabetes Center, University of California, San Francisco, 513 Parnassus Ave, San Francisco, California 94143-0534, USA.)

  • Shamil Sunyaev

    (The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
    Brigham & Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
    Harvard Medical School, 25 Shattuck St, Boston, Massachusetts 02115, USA.)

  • James A. Thomson

    (University of Wisconsin
    Morgridge Institute for Research, 330 N. Orchard Street, Madison, Wisconsin 53707, USA.)

  • Thea D. Tlsty

    (University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0511, USA.)

  • Li-Huei Tsai

    (The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
    The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, Massachusetts 02139, USA.)

  • Wei Wang

    (Institute of Genomic Medicine, Moores Cancer Center, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.)

  • Robert A. Waterland

    (USDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, Texas 77030, USA.)

  • Michael Q. Zhang

    (Center for Systems Biology, The University of Texas, Dallas, NSERL, RL10, 800 W Campbell Road, Richardson, Texas 75080, USA.
    Center for Synthetic and Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China.)

  • Lisa H. Chadwick

    (National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, North Carolina 27709, USA.)

  • Bradley E. Bernstein

    (The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
    Massachusetts General Hospital, 55 Fruit St, Boston, Massachusetts 02114, USA.
    Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland 20815-6789, USA.)

  • Joseph F. Costello

    (Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1450 3rd Street, San Francisco, California 94158, USA.)

  • Joseph R. Ecker

    (Genomic Analysis Laboratory, Howard Hughes Medical Institute & The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA.)

  • Martin Hirst

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
    University of British Columbia, 2125 East Mall, Vancouver, British Columbia V6T 1Z4, Canada.)

  • Alexander Meissner

    (The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.
    7 Divinity Ave, Cambridge, Massachusetts 02138, USA.)

  • Aleksandar Milosavljevic

    (Epigenome Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.)

  • Bing Ren

    (Institute of Genomic Medicine, Moores Cancer Center, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093, USA.)

  • John A. Stamatoyannopoulos

    (University of Washington, 3720 15th Ave. NE, Seattle, Washington 98195, USA.)

  • Ting Wang

    (Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA.)

  • Manolis Kellis

    (Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA.
    The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.)

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.

Suggested Citation

  • Anshul Kundaje & Wouter Meuleman & Jason Ernst & Misha Bilenky & Angela Yen & Alireza Heravi-Moussavi & Pouya Kheradpour & Zhizhuo Zhang & Jianrong Wang & Michael J. Ziller & Viren Amin & John W. Whit, 2015. "Integrative analysis of 111 reference human epigenomes," Nature, Nature, vol. 518(7539), pages 317-330, February.
    • Handle: RePEc:nat:nature:v:518:y:2015:i:7539:d:10.1038_nature14248
    DOI: 10.1038/nature14248
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    Cited by:

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