title: GREAT improves functional interpretation of cis-regulatory regions.
abstract: We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome. Whereas previous methods took into account only binding proximal to genes, GREAT is able to properly incorporate distal binding sites and control for false positives using a binomial test over the input genomic regions. GREAT incorporates annotations from 20 ontologies and is available as a web application. Applying GREAT to data sets from chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) of multiple transcription-associated factors, including SRF, NRSF, GABP, Stat3 and p300 in different developmental contexts, we recover many functions of these factors that are missed by existing gene-based tools, and we generate testable hypotheses. The utility of GREAT is not limited to ChIP-seq, as it could also be applied to open chromatin, localized epigenomic markers and similar functional data sets, as well as comparative genomics sets.
authors.affiliation: Department of Computer Science, Stanford University, Stanford, California, USA.
authors.forename: Cory Y
authors.initials: CY
authors.lastname: McLean
authors.forename: Dave
authors.initials: D
authors.lastname: Bristor
authors.forename: Michael
authors.initials: M
authors.lastname: Hiller
authors.forename: Shoa L
authors.initials: SL
authors.lastname: Clarke
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Schaar
authors.forename: Craig B
authors.initials: CB
authors.lastname: Lowe
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Wenger
authors.forename: Gill
authors.initials: G
authors.lastname: Bejerano
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D057225:Data Mining / Q000379:methods*; D030541:Databases, Genetic; D050881:E1A-Associated p300 Protein; D016678:Genome; D023281:Genomics / Q000379:methods*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D011485:Protein Binding; D050436:Regulatory Elements, Transcriptional; D026362:Serum Response Factor; D012984:Software
chemical_list: D026362:Serum Response Factor; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse