Cargando…

Integrative annotation of chromatin elements from ENCODE data

The ENCODE Project has generated a wealth of experimental information mapping diverse chromatin properties in several human cell lines. Although each such data track is independently informative toward the annotation of regulatory elements, their interrelations contain much richer information for th...

Descripción completa

Detalles Bibliográficos
Autores principales: Hoffman, Michael M., Ernst, Jason, Wilder, Steven P., Kundaje, Anshul, Harris, Robert S., Libbrecht, Max, Giardine, Belinda, Ellenbogen, Paul M., Bilmes, Jeffrey A., Birney, Ewan, Hardison, Ross C., Dunham, Ian, Kellis, Manolis, Noble, William Stafford
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553955/
https://www.ncbi.nlm.nih.gov/pubmed/23221638
http://dx.doi.org/10.1093/nar/gks1284
_version_ 1782256847266250752
author Hoffman, Michael M.
Ernst, Jason
Wilder, Steven P.
Kundaje, Anshul
Harris, Robert S.
Libbrecht, Max
Giardine, Belinda
Ellenbogen, Paul M.
Bilmes, Jeffrey A.
Birney, Ewan
Hardison, Ross C.
Dunham, Ian
Kellis, Manolis
Noble, William Stafford
author_facet Hoffman, Michael M.
Ernst, Jason
Wilder, Steven P.
Kundaje, Anshul
Harris, Robert S.
Libbrecht, Max
Giardine, Belinda
Ellenbogen, Paul M.
Bilmes, Jeffrey A.
Birney, Ewan
Hardison, Ross C.
Dunham, Ian
Kellis, Manolis
Noble, William Stafford
author_sort Hoffman, Michael M.
collection PubMed
description The ENCODE Project has generated a wealth of experimental information mapping diverse chromatin properties in several human cell lines. Although each such data track is independently informative toward the annotation of regulatory elements, their interrelations contain much richer information for the systematic annotation of regulatory elements. To uncover these interrelations and to generate an interpretable summary of the massive datasets of the ENCODE Project, we apply unsupervised learning methodologies, converting dozens of chromatin datasets into discrete annotation maps of regulatory regions and other chromatin elements across the human genome. These methods rediscover and summarize diverse aspects of chromatin architecture, elucidate the interplay between chromatin activity and RNA transcription, and reveal that a large proportion of the genome lies in a quiescent state, even across multiple cell types. The resulting annotation of non-coding regulatory elements correlate strongly with mammalian evolutionary constraint, and provide an unbiased approach for evaluating metrics of evolutionary constraint in human. Lastly, we use the regulatory annotations to revisit previously uncharacterized disease-associated loci, resulting in focused, testable hypotheses through the lens of the chromatin landscape.
format Online
Article
Text
id pubmed-3553955
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-35539552013-01-24 Integrative annotation of chromatin elements from ENCODE data Hoffman, Michael M. Ernst, Jason Wilder, Steven P. Kundaje, Anshul Harris, Robert S. Libbrecht, Max Giardine, Belinda Ellenbogen, Paul M. Bilmes, Jeffrey A. Birney, Ewan Hardison, Ross C. Dunham, Ian Kellis, Manolis Noble, William Stafford Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics The ENCODE Project has generated a wealth of experimental information mapping diverse chromatin properties in several human cell lines. Although each such data track is independently informative toward the annotation of regulatory elements, their interrelations contain much richer information for the systematic annotation of regulatory elements. To uncover these interrelations and to generate an interpretable summary of the massive datasets of the ENCODE Project, we apply unsupervised learning methodologies, converting dozens of chromatin datasets into discrete annotation maps of regulatory regions and other chromatin elements across the human genome. These methods rediscover and summarize diverse aspects of chromatin architecture, elucidate the interplay between chromatin activity and RNA transcription, and reveal that a large proportion of the genome lies in a quiescent state, even across multiple cell types. The resulting annotation of non-coding regulatory elements correlate strongly with mammalian evolutionary constraint, and provide an unbiased approach for evaluating metrics of evolutionary constraint in human. Lastly, we use the regulatory annotations to revisit previously uncharacterized disease-associated loci, resulting in focused, testable hypotheses through the lens of the chromatin landscape. Oxford University Press 2013-01 2012-12-05 /pmc/articles/PMC3553955/ /pubmed/23221638 http://dx.doi.org/10.1093/nar/gks1284 Text en © The Author(s) 2012. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.
spellingShingle Gene Regulation, Chromatin and Epigenetics
Hoffman, Michael M.
Ernst, Jason
Wilder, Steven P.
Kundaje, Anshul
Harris, Robert S.
Libbrecht, Max
Giardine, Belinda
Ellenbogen, Paul M.
Bilmes, Jeffrey A.
Birney, Ewan
Hardison, Ross C.
Dunham, Ian
Kellis, Manolis
Noble, William Stafford
Integrative annotation of chromatin elements from ENCODE data
title Integrative annotation of chromatin elements from ENCODE data
title_full Integrative annotation of chromatin elements from ENCODE data
title_fullStr Integrative annotation of chromatin elements from ENCODE data
title_full_unstemmed Integrative annotation of chromatin elements from ENCODE data
title_short Integrative annotation of chromatin elements from ENCODE data
title_sort integrative annotation of chromatin elements from encode data
topic Gene Regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553955/
https://www.ncbi.nlm.nih.gov/pubmed/23221638
http://dx.doi.org/10.1093/nar/gks1284
work_keys_str_mv AT hoffmanmichaelm integrativeannotationofchromatinelementsfromencodedata
AT ernstjason integrativeannotationofchromatinelementsfromencodedata
AT wilderstevenp integrativeannotationofchromatinelementsfromencodedata
AT kundajeanshul integrativeannotationofchromatinelementsfromencodedata
AT harrisroberts integrativeannotationofchromatinelementsfromencodedata
AT libbrechtmax integrativeannotationofchromatinelementsfromencodedata
AT giardinebelinda integrativeannotationofchromatinelementsfromencodedata
AT ellenbogenpaulm integrativeannotationofchromatinelementsfromencodedata
AT bilmesjeffreya integrativeannotationofchromatinelementsfromencodedata
AT birneyewan integrativeannotationofchromatinelementsfromencodedata
AT hardisonrossc integrativeannotationofchromatinelementsfromencodedata
AT dunhamian integrativeannotationofchromatinelementsfromencodedata
AT kellismanolis integrativeannotationofchromatinelementsfromencodedata
AT noblewilliamstafford integrativeannotationofchromatinelementsfromencodedata