IdentifyFuncDomainEncode_GR07

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10.1101/gr.6081407 Access the most recent version at doi: 2007 17: 917-927 Genome Res. Robert E. Thurman, Nathan Day, William S. Noble, et al. ENCODE regions Identification of higher-order functional domains in the human Material Supplemental http://genome.cshlp.org/content/suppl/2007/05/23/17.6.917.DC1.html References http://genome.cshlp.org/content/17/6/917.full.html#related-urls Article cited in: http://genome.cshlp.org/content/17/6/917.full.html#ref-list-1 This article cites 45 articles, 17 of which can be accessed free at: Open Access Freely available online through the Genome Research Open Access option. service Email alerting click here top right corner of the article or Receive free email alerts when new articles cite this article - sign up in the box at the http://genome.cshlp.org/subscriptions go to: Genome Research To subscribe to Copyright © 2007, Cold Spring Harbor Laboratory Press Cold Spring Harbor Laboratory Press on November 5, 2009 - Published by genome.cshlp.org Downloaded from
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Identification of higher-order functional domains in the human ENCODE regions Robert E. Thurman, 1,2 Nathan Day, 3 William S. Noble, 2,3 and John A. Stamatoyannopoulos 2,4 1 Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA; 2 Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA; 3 Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA It has long been posited that human and other large genomes are organized into higher-order (i.e., greater than gene-sized) functional domains. We hypothesized that diverse experimental data types generated by The ENCODE Project Consortium could be combined to delineate active and quiescent or repressed functional domains and thereby illuminate the higher-order functional architecture of the genome. To address this, we coupled wavelet analysis with hidden Markov models for unbiased discovery of “domain-level” behavior in high-resolution functional genomic data, including activating and repressive histone modifications, RNA output, and DNA replication timing. We find that higher-order patterns in these data types are largely concordant and may be analyzed collectively in the context of HeLa cells to delineate 53 active and 62 repressed functional domains within the ENCODE regions. Active domains comprise 44% of the ENCODE regions but contain 75%–80% of annotated genes, transcripts, and CpG islands. Repressed domains are enriched in certain classes of repetitive elements and, surprisingly, in evolutionarily conserved nonexonic sequences. The functional domain structure of the ENCODE regions appears to be largely stable across different cell types. Taken together, our results suggest that higher-order functional domains represent a fundamental organizing principle of human genome architecture. [Supplemental material is available online at www.genome.org.]
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This note was uploaded on 04/06/2010 for the course COMPUTER S COSC1520 taught by Professor Paul during the Spring '09 term at York University.

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