Integrative analysis of 111 reference human epigenomes

A. Kundaje; W. Meuleman; J. Ernst; M. Bilenky; A. Yen; A. Heravi-Moussavi; P. Kheradpour; Z. Zhang; J. Wang; M.J. Ziller; V. Amin; J.W. Whitaker; M.D. Schultz; L.D. Ward; A. Sarkar; G. Quon; R.S. Sandstrom; M.L. Eaton; Y.C. Wu; A.R. Pfenning; X. Wang; M. Claussnitzer; Y. Liu; C. Coarfa; R.A. Harris; N. Shoresh; C.B. Epstein; E. Gjoneska; D. Leung; W. Xie; R.D. Hawkins; Ryan Lister; C. Hong; P. Gascard; A.J. Mungall; R. Moore; E. Chuah; A. Tam; T.K. Canfield; R.S. Hansen; R. Kaul; P.J. Sabo; M.S. Bansal; A. Carles; J.R. Dixon; K.H. Farh; S. Feizi; R. Karlic; A.R. Kim; A. Kulkarni; D. Li; R. Lowdon; G. Elliott; T.R. Mercer; S.J. Neph; V. Onuchic; P. Polak; N. Rajagopal; P. Ray; R.C. Sallari; K.T. Siebenthall; N.A. Sinnott-Armstrong; M. Stevens; R.E. Thurman; J. Wu; X. Zhou; A.E. Beaudet; L.A. Boyer; P.L. De Jager; P.J. Farnham; S.J. Fisher; D. Haussler; S.J.M. Jones; W. Li; M.A. Marra; M.T. Mcmanus; S. Sunyaev; J.A. Thomson; T.D. Tlsty; L.H. Tsai; W. Wang; R.A. Waterland; M.Q. Zhang; L.H. Chadwick; B.E. Bernstein; J.F. Costello; J.R. Ecker; M. Hirst; A. Meissner; A. Milosavljevic; B. Ren; J.A. Stamatoyannopoulos; T. Wang; M. Kellis; Bo Zhang

doi:10.1038/nature14248

Integrative analysis of 111 reference human epigenomes

A. Kundaje, W. Meuleman, J. Ernst, M. Bilenky, A. Yen, A. Heravi-Moussavi, P. Kheradpour, Z. Zhang, J. Wang, M.J. Ziller, V. Amin, J.W. Whitaker, M.D. Schultz, L.D. Ward, A. Sarkar, G. Quon, R.S. Sandstrom, M.L. Eaton, Y.C. Wu, A.R. PfenningX. Wang, M. Claussnitzer, Y. Liu, C. Coarfa, R.A. Harris, N. Shoresh, C.B. Epstein, E. Gjoneska, D. Leung, W. Xie, R.D. Hawkins, Ryan Lister, C. Hong, P. Gascard, A.J. Mungall, R. Moore, E. Chuah, A. Tam, T.K. Canfield, R.S. Hansen, R. Kaul, P.J. Sabo, M.S. Bansal, A. Carles, J.R. Dixon, K.H. Farh, S. Feizi, R. Karlic, A.R. Kim, A. Kulkarni, D. Li, R. Lowdon, G. Elliott, T.R. Mercer, S.J. Neph, V. Onuchic, P. Polak, N. Rajagopal, P. Ray, R.C. Sallari, K.T. Siebenthall, N.A. Sinnott-Armstrong, M. Stevens, R.E. Thurman, J. Wu, X. Zhou, A.E. Beaudet, L.A. Boyer, P.L. De Jager, P.J. Farnham, S.J. Fisher, D. Haussler, S.J.M. Jones, W. Li, M.A. Marra, M.T. Mcmanus, S. Sunyaev, J.A. Thomson, T.D. Tlsty, L.H. Tsai, W. Wang, R.A. Waterland, M.Q. Zhang, L.H. Chadwick, B.E. Bernstein, J.F. Costello, J.R. Ecker, M. Hirst, A. Meissner, A. Milosavljevic, B. Ren, J.A. Stamatoyannopoulos, T. Wang, M. Kellis, Bo Zhang

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Abstract

© 2015 Macmillan Publishers Limited. 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
Pages (from-to)	317-329
Journal	Nature
Volume	518
Issue number	7539
DOIs	https://doi.org/10.1038/nature14248
Publication status	Published - 2015

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10.1038/nature14248

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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., Wu, Y. C., ... Zhang, B. (2015). Integrative analysis of 111 reference human epigenomes. Nature, 518(7539), 317-329. https://doi.org/10.1038/nature14248

@article{169d3ae62e4a4ffba1d21fed6f24bae5,

title = "Integrative analysis of 111 reference human epigenomes",

abstract = "{\textcopyright} 2015 Macmillan Publishers Limited. 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 = "A. Kundaje and W. Meuleman and J. Ernst and M. Bilenky and A. Yen and A. Heravi-Moussavi and P. Kheradpour and Z. Zhang and J. Wang and M.J. Ziller and V. Amin and J.W. Whitaker and M.D. Schultz and L.D. Ward and A. Sarkar and G. Quon and R.S. Sandstrom and M.L. Eaton and Y.C. Wu and A.R. Pfenning and X. Wang and M. Claussnitzer and Y. Liu and C. Coarfa and R.A. Harris and N. Shoresh and C.B. Epstein and E. Gjoneska and D. Leung and W. Xie and R.D. Hawkins and Ryan Lister and C. Hong and P. Gascard and A.J. Mungall and R. Moore and E. Chuah and A. Tam and T.K. Canfield and R.S. Hansen and R. Kaul and P.J. Sabo and M.S. Bansal and A. Carles and J.R. Dixon and K.H. Farh and S. Feizi and R. Karlic and A.R. Kim and A. Kulkarni and D. Li and R. Lowdon and G. Elliott and T.R. Mercer and S.J. Neph and V. Onuchic and P. Polak and N. Rajagopal and P. Ray and R.C. Sallari and K.T. Siebenthall and N.A. Sinnott-Armstrong and M. Stevens and R.E. Thurman and J. Wu and X. Zhou and A.E. Beaudet and L.A. Boyer and {De Jager}, P.L. and P.J. Farnham and S.J. Fisher and D. Haussler and S.J.M. Jones and W. Li and M.A. Marra and M.T. Mcmanus and S. Sunyaev and J.A. Thomson and T.D. Tlsty and L.H. Tsai and W. Wang and R.A. Waterland and M.Q. Zhang and L.H. Chadwick and B.E. Bernstein and J.F. Costello and J.R. Ecker and M. Hirst and A. Meissner and A. Milosavljevic and B. Ren and J.A. Stamatoyannopoulos and T. Wang and M. Kellis and Bo Zhang",

year = "2015",

doi = "10.1038/nature14248",

language = "English",

volume = "518",

pages = "317--329",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group - Macmillan Publishers",

number = "7539",

}

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, 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 & Zhang, B 2015, 'Integrative analysis of 111 reference human epigenomes', Nature, vol. 518, no. 7539, pp. 317-329. https://doi.org/10.1038/nature14248

TY - JOUR

T1 - Integrative analysis of 111 reference human epigenomes

AU - Kundaje, A.

AU - Meuleman, W.

AU - Ernst, J.

AU - Bilenky, M.

AU - Yen, A.

AU - Heravi-Moussavi, A.

AU - Kheradpour, P.

AU - Zhang, Z.

AU - Wang, J.

AU - Ziller, M.J.

AU - Amin, V.

AU - Whitaker, J.W.

AU - Schultz, M.D.

AU - Ward, L.D.

AU - Sarkar, A.

AU - Quon, G.

AU - Sandstrom, R.S.

AU - Eaton, M.L.

AU - Wu, Y.C.

AU - Pfenning, A.R.

AU - Wang, X.

AU - Claussnitzer, M.

AU - Liu, Y.

AU - Coarfa, C.

AU - Harris, R.A.

AU - Shoresh, N.

AU - Epstein, C.B.

AU - Gjoneska, E.

AU - Leung, D.

AU - Xie, W.

AU - Hawkins, R.D.

AU - Lister, Ryan

AU - Hong, C.

AU - Gascard, P.

AU - Mungall, A.J.

AU - Moore, R.

AU - Chuah, E.

AU - Tam, A.

AU - Canfield, T.K.

AU - Hansen, R.S.

AU - Kaul, R.

AU - Sabo, P.J.

AU - Bansal, M.S.

AU - Carles, A.

AU - Dixon, J.R.

AU - Farh, K.H.

AU - Feizi, S.

AU - Karlic, R.

AU - Kim, A.R.

AU - Kulkarni, A.

AU - Li, D.

AU - Lowdon, R.

AU - Elliott, G.

AU - Mercer, T.R.

AU - Neph, S.J.

AU - Onuchic, V.

AU - Polak, P.

AU - Rajagopal, N.

AU - Ray, P.

AU - Sallari, R.C.

AU - Siebenthall, K.T.

AU - Sinnott-Armstrong, N.A.

AU - Stevens, M.

AU - Thurman, R.E.

AU - Wu, J.

AU - Zhou, X.

AU - Beaudet, A.E.

AU - Boyer, L.A.

AU - De Jager, P.L.

AU - Farnham, P.J.

AU - Fisher, S.J.

AU - Haussler, D.

AU - Jones, S.J.M.

AU - Li, W.

AU - Marra, M.A.

AU - Mcmanus, M.T.

AU - Sunyaev, S.

AU - Thomson, J.A.

AU - Tlsty, T.D.

AU - Tsai, L.H.

AU - Wang, W.

AU - Waterland, R.A.

AU - Zhang, M.Q.

AU - Chadwick, L.H.

AU - Bernstein, B.E.

AU - Costello, J.F.

AU - Ecker, J.R.

AU - Hirst, M.

AU - Meissner, A.

AU - Milosavljevic, A.

AU - Ren, B.

AU - Stamatoyannopoulos, J.A.

AU - Wang, T.

AU - Kellis, M.

AU - Zhang, Bo

PY - 2015

Y1 - 2015

N2 - © 2015 Macmillan Publishers Limited. 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 - © 2015 Macmillan Publishers Limited. 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.

U2 - 10.1038/nature14248

DO - 10.1038/nature14248

M3 - Article

C2 - 25693563

SN - 0028-0836

VL - 518

SP - 317

EP - 329

JO - Nature

JF - Nature

IS - 7539

ER -

Integrative analysis of 111 reference human epigenomes

Abstract

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