Integrative analysis of 111 reference human epigenomes

Epigenomics Consortium Roadmap Epigenomics Consortium; 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. Whitaker; Matthew D. Schultz; Lucas D. Ward; Abhishek Sarkar; Gerald Quon; Richard S. Sandstrom; Matthew L. Eaton; Yi Chieh Wu; Andreas R. Pfenning; Xinchen Wang; Melina Claussnitzer; Yaping Liu; Cristian Coarfa; R. Alan Harris; Noam Shoresh; Charles B. Epstein; Elizabeta Gjoneska; Danny Leung; Wei Xie; R. David Hawkins; Ryan Lister; Chibo Hong; Philippe Gascard; Andrew J. Mungall; Richard Moore; Eric Chuah; Angela Tam; Theresa K. Canfield; R. Scott Hansen; Rajinder Kaul; Peter J. Sabo; Mukul S. Bansal; Annaick Carles; Jesse R. Dixon; Kai How Farh; Soheil Feizi; Rosa Karlic; Ah Ram Kim; Ashwinikumar Kulkarni; Daofeng Li; Rebecca Lowdon; Ginell Elliott; Tim R. Mercer; Shane J. Neph; Vitor Onuchic; Paz Polak; Nisha Rajagopal; Pradipta Ray; Richard C. Sallari; Kyle T. Siebenthall; Nicholas A. Sinnott-Armstrong; Michael Stevens; Robert E. Thurman; Jie Wu; Bo Zhang; Xin Zhou; Arthur E. Beaudet; Laurie A. Boyer; Philip L. De Jager; Peggy J. Farnham; Susan J. Fisher; David Haussler; Steven J.M. Jones; Wei Li; Marco A. Marra; Michael T. McManus; Shamil Sunyaev; James A. Thomson; Thea D. Tlsty; Li Huei Tsai; Wei Wang; Robert A. Waterland; Michael Q. Zhang; Lisa H. Chadwick; Bradley E. Bernstein; Joseph F. Costello; Joseph R. Ecker; Martin Hirst; Alexander Meissner; Aleksandar Milosavljevic; Bing Ren; John A. Stamatoyannopoulos; Ting Wang; Manolis Kellis

doi:10.1038/nature14248

Integrative analysis of 111 reference human epigenomes

Epigenomics Consortium Roadmap Epigenomics Consortium, 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. Whitaker, Matthew D. Schultz, Lucas D. Ward, Abhishek Sarkar, Gerald Quon, Richard S. Sandstrom, Matthew L. Eaton, Yi Chieh WuAndreas R. Pfenning, Xinchen Wang, Melina Claussnitzer, Yaping Liu, Cristian Coarfa, R. Alan Harris, Noam Shoresh, Charles B. Epstein, Elizabeta Gjoneska, Danny Leung, Wei Xie, R. David Hawkins, Ryan Lister, Chibo Hong, Philippe Gascard, Andrew J. Mungall, Richard Moore, Eric Chuah, Angela Tam, Theresa K. Canfield, R. Scott Hansen, Rajinder Kaul, Peter J. Sabo, Mukul S. Bansal, Annaick Carles, Jesse R. Dixon, Kai How Farh, Soheil Feizi, Rosa Karlic, Ah Ram Kim, Ashwinikumar Kulkarni, Daofeng Li, Rebecca Lowdon, Ginell Elliott, Tim R. Mercer, Shane J. Neph, Vitor Onuchic, Paz Polak, Nisha Rajagopal, Pradipta Ray, Richard C. Sallari, Kyle T. Siebenthall, Nicholas A. Sinnott-Armstrong, Michael Stevens, Robert E. Thurman, Jie Wu, Bo Zhang, Xin Zhou, Arthur E. Beaudet, Laurie A. Boyer, Philip L. De Jager, Peggy J. Farnham, Susan J. Fisher, David Haussler, Steven J.M. Jones, Wei Li, Marco A. Marra, Michael T. McManus, Shamil Sunyaev, James A. Thomson, Thea D. Tlsty, Li Huei Tsai, Wei Wang, Robert A. Waterland, Michael Q. Zhang, Lisa H. Chadwick, Bradley E. Bernstein, Joseph F. Costello, Joseph R. Ecker, Martin Hirst, Alexander Meissner, Aleksandar Milosavljevic, Bing Ren, John A. Stamatoyannopoulos, Ting Wang, Manolis Kellis

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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.

Original language	English (US)
Pages (from-to)	317-329
Number of pages	13
Journal	Nature
Volume	518
Issue number	7539
DOIs	https://doi.org/10.1038/nature14248
State	Published - Feb 19 2015
Externally published	Yes

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10.1038/nature14248

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Roadmap Epigenomics Consortium, E. C., Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., Ziller, M. J., Amin, V., Whitaker, J. W., Schultz, M. D., Ward, L. D., Sarkar, A., Quon, G., Sandstrom, R. S., Eaton, M. L., ... Kellis, M. (2015). Integrative analysis of 111 reference human epigenomes. Nature, 518(7539), 317-329. https://doi.org/10.1038/nature14248

Roadmap Epigenomics Consortium, EC, Kundaje, A, Meuleman, W, Ernst, J, Bilenky, M, Yen, A, Heravi-Moussavi, A, Kheradpour, P, Zhang, Z, Wang, J, Ziller, MJ, Amin, V, Whitaker, JW, Schultz, MD, Ward, LD, Sarkar, A, Quon, G, Sandstrom, RS, Eaton, ML, Wu, YC, Pfenning, AR, Wang, X, Claussnitzer, M, Liu, Y, Coarfa, C, Harris, RA, Shoresh, N, Epstein, CB, Gjoneska, E, Leung, D, Xie, W, Hawkins, RD, Lister, R, Hong, C, Gascard, P, Mungall, AJ, Moore, R, Chuah, E, Tam, A, Canfield, TK, Hansen, RS, Kaul, R, Sabo, PJ, Bansal, MS, Carles, A, Dixon, JR, Farh, KH, Feizi, S, Karlic, R, Kim, AR, Kulkarni, A, Li, D, Lowdon, R, Elliott, G, Mercer, TR, Neph, SJ, Onuchic, V, Polak, P, Rajagopal, N, Ray, P, Sallari, RC, Siebenthall, KT, Sinnott-Armstrong, NA, Stevens, M, Thurman, RE, Wu, J, Zhang, B, Zhou, X, Beaudet, AE, Boyer, LA, De Jager, PL, Farnham, PJ, Fisher, SJ, Haussler, D, Jones, SJM, Li, W, Marra, MA, McManus, MT, Sunyaev, S, Thomson, JA, Tlsty, TD, Tsai, LH, Wang, W, Waterland, RA, Zhang, MQ, Chadwick, LH, Bernstein, BE, Costello, JF, Ecker, JR, Hirst, M, Meissner, A, Milosavljevic, A, Ren, B, Stamatoyannopoulos, JA, Wang, T & Kellis, M 2015, 'Integrative analysis of 111 reference human epigenomes', Nature, vol. 518, no. 7539, pp. 317-329. https://doi.org/10.1038/nature14248

@article{1f9e30fa9bec45cea69cfe274641eb79,

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.",

author = "{Roadmap Epigenomics Consortium}, {Epigenomics Consortium} and Anshul Kundaje and Wouter Meuleman and Jason Ernst and Misha Bilenky and Angela Yen and Alireza Heravi-Moussavi and Pouya Kheradpour and Zhizhuo Zhang and Jianrong Wang and Ziller, {Michael J.} and Viren Amin and Whitaker, {John W.} and Schultz, {Matthew D.} and Ward, {Lucas D.} and Abhishek Sarkar and Gerald Quon and Sandstrom, {Richard S.} and Eaton, {Matthew L.} and Wu, {Yi Chieh} and Pfenning, {Andreas R.} and Xinchen Wang and Melina Claussnitzer and Yaping Liu and Cristian Coarfa and Harris, {R. Alan} and Noam Shoresh and Epstein, {Charles B.} and Elizabeta Gjoneska and Danny Leung and Wei Xie and Hawkins, {R. David} and Ryan Lister and Chibo Hong and Philippe Gascard and Mungall, {Andrew J.} and Richard Moore and Eric Chuah and Angela Tam and Canfield, {Theresa K.} and Hansen, {R. Scott} and Rajinder Kaul and Sabo, {Peter J.} and Bansal, {Mukul S.} and Annaick Carles and Dixon, {Jesse R.} and Farh, {Kai How} and Soheil Feizi and Rosa Karlic and Kim, {Ah Ram} and Ashwinikumar Kulkarni and Daofeng Li and Rebecca Lowdon and Ginell Elliott and Mercer, {Tim R.} and Neph, {Shane J.} and Vitor Onuchic and Paz Polak and Nisha Rajagopal and Pradipta Ray and Sallari, {Richard C.} and Siebenthall, {Kyle T.} and Sinnott-Armstrong, {Nicholas A.} and Michael Stevens and Thurman, {Robert E.} and Jie Wu and Bo Zhang and Xin Zhou and Beaudet, {Arthur E.} and Boyer, {Laurie A.} and {De Jager}, {Philip L.} and Farnham, {Peggy J.} and Fisher, {Susan J.} and David Haussler and Jones, {Steven J.M.} and Wei Li and Marra, {Marco A.} and McManus, {Michael T.} and Shamil Sunyaev and Thomson, {James A.} and Tlsty, {Thea D.} and Tsai, {Li Huei} and Wei Wang and Waterland, {Robert A.} and Zhang, {Michael Q.} and Chadwick, {Lisa H.} and Bernstein, {Bradley E.} and Costello, {Joseph F.} and Ecker, {Joseph R.} and Martin Hirst and Alexander Meissner and Aleksandar Milosavljevic and Bing Ren and Stamatoyannopoulos, {John A.} and Ting Wang and Manolis Kellis",

note = "Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

year = "2015",

month = feb,

day = "19",

doi = "10.1038/nature14248",

language = "English (US)",

volume = "518",

pages = "317--329",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7539",

}

TY - JOUR

T1 - Integrative analysis of 111 reference human epigenomes

AU - Roadmap Epigenomics Consortium, Epigenomics Consortium

AU - Kundaje, Anshul

AU - Meuleman, Wouter

AU - Ernst, Jason

AU - Bilenky, Misha

AU - Yen, Angela

AU - Heravi-Moussavi, Alireza

AU - Kheradpour, Pouya

AU - Zhang, Zhizhuo

AU - Wang, Jianrong

AU - Ziller, Michael J.

AU - Amin, Viren

AU - Whitaker, John W.

AU - Schultz, Matthew D.

AU - Ward, Lucas D.

AU - Sarkar, Abhishek

AU - Quon, Gerald

AU - Sandstrom, Richard S.

AU - Eaton, Matthew L.

AU - Wu, Yi Chieh

AU - Pfenning, Andreas R.

AU - Wang, Xinchen

AU - Claussnitzer, Melina

AU - Liu, Yaping

AU - Coarfa, Cristian

AU - Harris, R. Alan

AU - Shoresh, Noam

AU - Epstein, Charles B.

AU - Gjoneska, Elizabeta

AU - Leung, Danny

AU - Xie, Wei

AU - Hawkins, R. David

AU - Lister, Ryan

AU - Hong, Chibo

AU - Gascard, Philippe

AU - Mungall, Andrew J.

AU - Moore, Richard

AU - Chuah, Eric

AU - Tam, Angela

AU - Canfield, Theresa K.

AU - Hansen, R. Scott

AU - Kaul, Rajinder

AU - Sabo, Peter J.

AU - Bansal, Mukul S.

AU - Carles, Annaick

AU - Dixon, Jesse R.

AU - Farh, Kai How

AU - Feizi, Soheil

AU - Karlic, Rosa

AU - Kim, Ah Ram

AU - Kulkarni, Ashwinikumar

AU - Li, Daofeng

AU - Lowdon, Rebecca

AU - Elliott, Ginell

AU - Mercer, Tim R.

AU - Neph, Shane J.

AU - Onuchic, Vitor

AU - Polak, Paz

AU - Rajagopal, Nisha

AU - Ray, Pradipta

AU - Sallari, Richard C.

AU - Siebenthall, Kyle T.

AU - Sinnott-Armstrong, Nicholas A.

AU - Stevens, Michael

AU - Thurman, Robert E.

AU - Wu, Jie

AU - Zhang, Bo

AU - Zhou, Xin

AU - Beaudet, Arthur E.

AU - Boyer, Laurie A.

AU - De Jager, Philip L.

AU - Farnham, Peggy J.

AU - Fisher, Susan J.

AU - Haussler, David

AU - Jones, Steven J.M.

AU - Li, Wei

AU - Marra, Marco A.

AU - McManus, Michael T.

AU - Sunyaev, Shamil

AU - Thomson, James A.

AU - Tlsty, Thea D.

AU - Tsai, Li Huei

AU - Wang, Wei

AU - Waterland, Robert A.

AU - Zhang, Michael Q.

AU - Chadwick, Lisa H.

AU - Bernstein, Bradley E.

AU - Costello, Joseph F.

AU - Ecker, Joseph R.

AU - Hirst, Martin

AU - Meissner, Alexander

AU - Milosavljevic, Aleksandar

AU - Ren, Bing

AU - Stamatoyannopoulos, John A.

AU - Wang, Ting

AU - Kellis, Manolis

PY - 2015/2/19

Y1 - 2015/2/19

N2 - 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.

AB - 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=84923362619&partnerID=8YFLogxK

U2 - 10.1038/nature14248

DO - 10.1038/nature14248

M3 - Article

C2 - 25693563

AN - SCOPUS:84923362619

SN - 0028-0836

VL - 518

SP - 317

EP - 329

JO - Nature

JF - Nature

IS - 7539

ER -

Integrative analysis of 111 reference human epigenomes

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