A User ' s Guide to the Encyclopedia of DNA Elements ( ENCODE )

The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome. Citation: The ENCODE Project Consortium (2011) A User’s Guide to the Encyclopedia of DNA Elements (ENCODE). PLoS Biol 9(4): e1001046. doi:10.1371/ journal.pbio. 1001046 Academic Editor: Peter B. Becker, Adolf Butenandt Institute, Germany Received September 23, 2010; Accepted March 10, 2011; Published April 19, 2011 Copyright: 2011 The ENCODE Project Consortium. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Funded by the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. The role of the NIH Project Management Group in the preparation of this paper was limited to coordination and scientific management of the ENCODE Consortium. Competing Interests: The authors have declared that no competing interests exist. Abbreviations: 3C, Chromosome Conformation Capture; API, application programming interface; CAGE, Cap-Analysis of Gene Expression; ChIP, chromatin immunoprecipitation; DCC, Data Coordination Center; DHS, DNaseI hypersensitive site; ENCODE, Encyclopedia of DNA Elements; EPO, Enredo, Pecan, Ortheus approach; FDR, false discovery rate; GEO, Gene Expression Omnibus; GWAS, genome-wide association studies; IDR, Irreproducible Discovery Rate; Methyl-seq, sequencing-based methylation determination assay; NHGRI, National Human Genome Research Institute; PASRs, promoter-associated short RNAs; PET, Paired-End diTag; RACE, Rapid Amplification of cDNA Ends; RNA Pol2, RNA polymerase 2; RBP, RNA-binding protein; RRBS, Reduced Representation Bisulfite Sequencing; SRA, Sequence Read Archive; TAS, trait/disease-associated SNP; TF, transcription factor; TSS, transcription start site * E-mail: rmyers@hudsonalpha.org (RMM); jstam@u.washington. edu (JS); mpsnyder@stanford.edu (MS); dunham@ebi.ac. uk (ID); rch8@psu.edu (RCH); bernstein. bradley@mgh.harvard. edu (BEB); gingeras@cshl.edu (TRG); kent@soe.ucsc. edu (WJK); birney@ebi.ac. uk (EB); woldb@caltech.edu (BW); greg.crawford@duke.edu (GEC) " Membership of the ENCODE Project Consortium is provided in the Acknowledgments.