Skip Navigation



Bioinformatics Advance Access published online on June 30, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn335
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
24/17/1911    most recent
btn335v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Lian, H.
Right arrow Articles by Lawrence, C. E.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lian, H.
Right arrow Articles by Lawrence, C. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Automated mapping of large-scale chromatin structure in ENCODE

Heng Lian 1, William A. Thompson 2, Robert Thurman 3, John A. Stamatoyannopoulos 4, William Stafford Noble 4,5 and Charles E. Lawrence 2,*

1Division of Mathematical Sciences, SPMS, Nanyang Technological University, Singapore, 2Center for Computational Molecular Biology, Division of Applied Mathematics, Brown University, Providence, RI, USA, 3Division of Medical Genetics, University of Washington, Seattle, WA, USA, 4Department of Genome Sciences, University of Washington, Seattle, WA, USA and 5Department of Computer Science and Engineering, University of Washington, Seattle, WA, USA

*To whom correspondence should be addressed. Charles E. Lawrence, E-mail: Charles_Lawrence{at}brown.edu


  Abstract

Motivation: A recently developed DNase I assay has given us our first genome-wide view of chromatin structure. In addition to cataloging DNase I hypersensitive sites, these data allows us to more completely characterize overall features of chromatin accessibility. We employed a Bayesian hierarchical change point model (CPM), a generalization of a hidden Markov Model, to characterize tiled microarray DNase I sensitivity data available from the ENCODE project.

Results: Our analysis shows that the accessibility of chromatin to cleavage by DNase I is well described by a four state model of local segments with each state described by a continuous mixture of Gaussian variables. The CPM produces a better fit to the observed data than the HMM. The large posterior probability for the fourstate CPM suggests that the data falls naturally into four classes of regions, which we call major and minor DNase I hypersensitive sites (DHSs), regions of intermediate sensitivity, and insensitive regions. These classes agree well with a model of chromatin in which local disruptions (DHSs) are concentrated within larger domains of intermediate sensitivity, the accessibility islands. The CPM assigns 92% of the bases within the ENCODE regions to the insensitive regions. The 5.8% of the bases that are in regions of intermediate sensitivity are clearly enriched in functional elements, including genes and activating histone modifications, while the remaining 2.2% of the bases in hypersensitive regions are very strongly enriched in these elements.

Availability: The CPM software is available upon request from the authors.

Contact: jstam{at}stamlab.org; wnoble{at}u.washington.edu; Charles_Lawrence{at}brown.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Dr. Jonathan Wren

Received on May 15, 2008; revised on June 28, 2008; accepted on June 28, 2008

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.