title: Integrative annotation of chromatin elements from ENCODE data.
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.
authors.affiliation: Department of Genome Sciences, University of Washington, 3720 15th Ave NE, Seattle, WA 98195-5065, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffman
authors.forename: Jason
authors.initials: J
authors.lastname: Ernst
authors.forename: Steven P
authors.initials: SP
authors.lastname: Wilder
authors.forename: Anshul
authors.initials: A
authors.lastname: Kundaje
authors.forename: Robert S
authors.initials: RS
authors.lastname: Harris
authors.forename: Max
authors.initials: M
authors.lastname: Libbrecht
authors.forename: Belinda
authors.initials: B
authors.lastname: Giardine
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ellenbogen
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bilmes
authors.forename: Ewan
authors.initials: E
authors.lastname: Birney
authors.forename: Ross C
authors.initials: RC
authors.lastname: Hardison
authors.forename: Ian
authors.initials: I
authors.lastname: Dunham
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.forename: William Stafford
authors.initials: WS
authors.lastname: Noble
mesh_terms: D002843:Chromatin / Q000737:chemistry*; D004742:Enhancer Elements, Genetic; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D038101:Insulator Elements; D058977:Molecular Sequence Annotation; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D050436:Regulatory Elements, Transcriptional; D013728:Terminator Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D011506:Proteins