Automated mapping of large-scale chromatin structure in ENCODE.

@article{citeulike:2961372, 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@stamlab.org; wnoble@u.washington.edu; Charles\_Lawrence@brown.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, address = {Division of Mathematical Sciences, SPMS, Nanyang Technological University, Singapore, Center for Computational Molecular Biology, Division of Applied Mathematics, Brown University, Providence, RI, USA, Division of Medical Genetics, University of Washington, Seattle, WA, USA, Department of Genome Sciences, University of Washington, Seattle, WA, USA and Department of Computer Science and Engineering, University of Washington, Seattle, WA, USA.}, author = {Lian, Heng and Thompson, William A A. and Thurman, Robert and Stamatoyannopoulos, John A A. and Noble, William Stafford S. and Lawrence, Charles E E. }, citeulike-article-id = {2961372}, doi = {http://dx.doi.org/10.1093/bioinformatics/btn335}, issn = {1460-2059}, journal = {Bioinformatics (Oxford, England)}, keywords = {annotation, epigenetics}, month = {June}, posted-at = {2008-07-03 22:27:20}, priority = {2}, title = {Automated mapping of large-scale chromatin structure in ENCODE.}, url = {http://dx.doi.org/10.1093/bioinformatics/btn335}, year = {2008} }

TY - JOUR ID - citeulike:2961372 L3 - citeulike-article-id:2961372 TI - Automated mapping of large-scale chromatin structure in ENCODE. JF - Bioinformatics (Oxford, England) AD - Division of Mathematical Sciences, SPMS, Nanyang Technological University, Singapore, Center for Computational Molecular Biology, Division of Applied Mathematics, Brown University, Providence, RI, USA, Division of Medical Genetics, University of Washington, Seattle, WA, USA, Department of Genome Sciences, University of Washington, Seattle, WA, USA and Department of Computer Science and Engineering, University of Washington, Seattle, WA, USA. SN - 1460-2059 N2 - 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@stamlab.org; wnoble@u.washington.edu; Charles_Lawrence@brown.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. KW - annotation KW - epigenetics AU - Lian, Heng AU - Thompson, William A AU - Thurman, Robert AU - Stamatoyannopoulos, John A AU - Noble, William Stafford AU - Lawrence, Charles E PY - 2008/06/30/ UR - http://dx.doi.org/10.1093/bioinformatics/btn335 ER -