Integrative annotation of chromatin elements from ENCODE data.

Nucleic Acids Res
Authors
Keywords
Abstract

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.

Year of Publication
2013
Journal
Nucleic Acids Res
Volume
41
Issue
2
Pages
827-41
Date Published
2013 Jan
ISSN
1362-4962
URL
DOI
10.1093/nar/gks1284
PubMed ID
23221638
PubMed Central ID
PMC3553955
Links
Grant list
DK065806 / 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