PMID- 20436461 OWN - NLM STAT- MEDLINE DCOM- 20100830 LR - 20230131 IS - 1546-1696 (Electronic) IS - 1087-0156 (Print) IS - 1087-0156 (Linking) VI - 28 IP - 5 DP - 2010 May TI - GREAT improves functional interpretation of cis-regulatory regions. PG - 495-501 LID - 10.1038/nbt.1630 [doi] AB - 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. FAU - McLean, Cory Y AU - McLean CY AD - Department of Computer Science, Stanford University, Stanford, California, USA. FAU - Bristor, Dave AU - Bristor D FAU - Hiller, Michael AU - Hiller M FAU - Clarke, Shoa L AU - Clarke SL FAU - Schaar, Bruce T AU - Schaar BT FAU - Lowe, Craig B AU - Lowe CB FAU - Wenger, Aaron M AU - Wenger AM FAU - Bejerano, Gill AU - Bejerano G LA - eng GR - R01 HD059862/HD/NICHD NIH HHS/United States GR - 1R01HD059862/HD/NICHD NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100502 PL - United States TA - Nat Biotechnol JT - Nature biotechnology JID - 9604648 RN - 0 (Serum Response Factor) RN - EC 2.3.1.48 (E1A-Associated p300 Protein) RN - EC 2.3.1.48 (Ep300 protein, mouse) SB - IM MH - Animals MH - Chromatin Immunoprecipitation MH - Data Mining/*methods MH - Databases, Genetic MH - E1A-Associated p300 Protein MH - *Genome MH - Genomics/*methods MH - Humans MH - Jurkat Cells MH - Mice MH - Protein Binding MH - *Regulatory Elements, Transcriptional MH - Serum Response Factor MH - *Software PMC - PMC4840234 MID - NIHMS768381 EDAT- 2010/05/04 06:00 MHDA- 2010/08/31 06:00 PMCR- 2016/04/22 CRDT- 2010/05/04 06:00 PHST- 2010/05/04 06:00 [entrez] PHST- 2010/05/04 06:00 [pubmed] PHST- 2010/08/31 06:00 [medline] PHST- 2016/04/22 00:00 [pmc-release] AID - nbt.1630 [pii] AID - 10.1038/nbt.1630 [doi] PST - ppublish SO - Nat Biotechnol. 2010 May;28(5):495-501. doi: 10.1038/nbt.1630. Epub 2010 May 2.