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Nucleic Acids Res DOI:10.1093/nar/gks1284

Integrative annotation of chromatin elements from ENCODE data.

Publication TypeJournal Article
Year of Publication2013
AuthorsHoffman, MM, Ernst, J, Wilder, SP, Kundaje, A, Harris, RS, Libbrecht, M, Giardine, B, Ellenbogen, PM, Bilmes, JA, Birney, E, Hardison, RC, Dunham, I, Kellis, M, Noble, WStafford
JournalNucleic Acids Res
Date Published2013 Jan
KeywordsChromatin, Enhancer Elements, Genetic, Genome, Human, Genome-Wide Association Study, Humans, Insulator Elements, Molecular Sequence Annotation, Promoter Regions, Genetic, Proteins, Regulatory Elements, Transcriptional, Terminator Regions, Genetic, Transcription, Genetic

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.


Alternate JournalNucleic Acids Res.
PubMed ID23221638
PubMed Central IDPMC3553955
Grant ListDK065806 / DK / NIDDK NIH HHS / United States
HG004695 / HG / NHGRI NIH HHS / United States
R01 HG004037 / HG / NHGRI NIH HHS / United States
RC2 HG005573 / HG / NHGRI NIH HHS / United States
HG006259 / HG / NHGRI NIH HHS / United States
HG005573 / HG / NHGRI NIH HHS / United States
HG005334 / HG / NHGRI NIH HHS / United States
HG004570 / HG / NHGRI NIH HHS / United States
095908 / / Wellcome Trust / United Kingdom
R01 DK065806 / DK / NIDDK NIH HHS / United States
K99 HG006259 / HG / NHGRI NIH HHS / United States