research highlights

GENOMICS The ENCODE project

The second, -wide phase of a particular product (for instance, a ENCODE-defined functional element in at the Encyclopedia of DNA Elements or noncoding RNA) or has a consistent bio- least one examined type; an even larger (ENCODE) project is being reported. chemical property (for instance, being bound fraction (99%) lies nearby such an element The function of most of the human by protein or having a particular biochemical (within 1.7 kilobases). An examination of genome is unknown. Protein-coding mark). previously identified disease-associated account for only a small fraction (about 3%) The laboratories in the ENCODE Project single-nucleotide polymorphisms shows that of the total genome sequence; most func- Consortium have developed and applied a they are enriched in ENCODE-annotated tional genomic sequences are likely to have huge range of sequencing-based techniques regions, suggesting hypotheses for functional regulatory roles. Understanding human to map functional elements across the consequences of single-nucleotide polymor- organization and regulation and their genome. To put it succinctly, the ENCODE phisms that can be further tested. impact on normal and disease project has mapped state and The data generated by ENCODE are vast requires that functional elements be mapped structure, three-dimensional genome organi- and can be only very briefly summarized and annotated across the genome. This is the zation, DNA methylation, fac- here. The collected ENCODE papers may goal of the ENCODE project. tor binding, RNA transcription and protein be examined at http://www.encodeproject. The initial 5-year pilot phase of the proj- expression genome wide. Experiments were org/ENCODE/pubs.html or explored with ect focused on 1% of the conducted in multiple cell types, with the a dedicated visualization tool at http://www. sequence. The second 5-year phase of highest priority given to widely studied cell .com/ENCODE/. ENCODE, which began in 2007 and is now lines but with the list also including a human Natalie de Souza coming to fruition, has extended the analy- embryonic stem cell line and, in some cases, RESEARCH PAPERS sis of functional elements genome wide. A primary cells. The ENCODE Project Consortium. An integrated functional element as defined by ENCODE It is striking that a large fraction (80%) encyclopedia of DNA elements in the human genome. is a genomic sequence that either encodes of the genome overlaps with at least one Nature 489, 57–74 (2012). © 2012 Nature America, Inc. All rights reserved. America, Inc. © 2012 Nature npg

1046 | VOL.9 NO.11 | NOVEMBER 2012 | nature methods