{"id":188,"date":"2014-11-07T21:06:22","date_gmt":"2014-11-07T21:06:22","guid":{"rendered":"http:\/\/blogs.discovery.wisc.edu\/sysbiojournalclub\/?p=188"},"modified":"2014-11-07T21:06:22","modified_gmt":"2014-11-07T21:06:22","slug":"11-12-14","status":"publish","type":"post","link":"https:\/\/blogs.discovery.wisc.edu\/sysbiojournalclub\/2014\/11\/07\/11-12-14\/","title":{"rendered":"11.12.14"},"content":{"rendered":"<h1 id=\"article-title-1\" style=\"font-weight: bold;color: #000000\">Detection of active transcription factor binding sites with the combination of DNase hypersensitivity and histone modifications<\/h1>\n<div class=\"contributors\" style=\"color: #000000\">\n<ol id=\"contrib-group-1\" class=\"contributor-list\" style=\"font-weight: bold;font-style: inherit\">\n<li id=\"contrib-1\" class=\"contributor\" style=\"font-weight: inherit;font-style: inherit\"><span class=\"name\" style=\"font-weight: inherit;font-style: inherit\"><a class=\"name-search\" style=\"font-weight: bold;font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/search?author1=Eduardo+G.+Gusmao&amp;sortspec=date&amp;submit=Submit\">Eduardo G. Gusmao<\/a><\/span><a id=\"xref-aff-1-1\" class=\"xref-aff\" style=\"font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/content\/30\/22\/3143.full?etoc#aff-1\"><sup style=\"font-weight: inherit;font-style: inherit\">1<\/sup><\/a><span class=\"xref-sep\" style=\"font-weight: inherit;font-style: inherit\">,<\/span><a id=\"xref-corresp-1-1\" class=\"xref-corresp\" style=\"font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/content\/30\/22\/3143.full?etoc#corresp-1\">*<\/a>,<\/li>\n<li id=\"contrib-2\" class=\"contributor\" style=\"font-weight: inherit;font-style: inherit\"><span class=\"name\" style=\"font-weight: inherit;font-style: inherit\"><a class=\"name-search\" style=\"font-weight: bold;font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/search?author1=Christoph+Dieterich&amp;sortspec=date&amp;submit=Submit\">Christoph Dieterich<\/a><\/span><a id=\"xref-aff-1-2\" class=\"xref-aff\" style=\"font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/content\/30\/22\/3143.full?etoc#aff-1\"><sup style=\"font-weight: inherit;font-style: inherit\">2<\/sup><\/a>,<\/li>\n<li id=\"contrib-3\" class=\"contributor\" style=\"font-weight: inherit;font-style: inherit\"><span class=\"name\" style=\"font-weight: inherit;font-style: inherit\"><a class=\"name-search\" style=\"font-weight: bold;font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/search?author1=Martin+Zenke&amp;sortspec=date&amp;submit=Submit\">Martin Zenke<\/a><\/span><a id=\"xref-aff-1-3\" class=\"xref-aff\" style=\"font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/content\/30\/22\/3143.full?etoc#aff-1\"><sup style=\"font-weight: inherit;font-style: inherit\">3<\/sup><\/a><span class=\"xref-sep\" style=\"font-weight: inherit;font-style: inherit\">,<\/span><a id=\"xref-aff-1-4\" class=\"xref-aff\" style=\"font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/content\/30\/22\/3143.full?etoc#aff-1\"><sup style=\"font-weight: inherit;font-style: inherit\">4<\/sup><\/a>\u00a0and<\/li>\n<li id=\"contrib-4\" class=\"last\" style=\"font-weight: inherit;font-style: inherit\"><span class=\"name\" style=\"font-weight: inherit;font-style: inherit\"><a class=\"name-search\" style=\"font-weight: bold;font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/search?author1=Ivan+G.+Costa&amp;sortspec=date&amp;submit=Submit\">Ivan G. Costa<\/a><\/span><a id=\"xref-aff-1-5\" class=\"xref-aff\" style=\"font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/content\/30\/22\/3143.full?etoc#aff-1\"><sup style=\"font-weight: inherit;font-style: inherit\">1<\/sup><\/a><span class=\"xref-sep\" style=\"font-weight: inherit;font-style: inherit\">,<\/span><a id=\"xref-aff-1-6\" class=\"xref-aff\" style=\"font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/content\/30\/22\/3143.full?etoc#aff-1\"><sup style=\"font-weight: inherit;font-style: inherit\">5<\/sup><\/a><span class=\"xref-sep\" style=\"font-weight: inherit;font-style: inherit\">,<\/span><a id=\"xref-aff-1-7\" class=\"xref-aff\" style=\"font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/content\/30\/22\/3143.full?etoc#aff-1\"><sup style=\"font-weight: inherit;font-style: inherit\">6<\/sup><\/a><span class=\"xref-sep\" style=\"font-weight: inherit;font-style: inherit\">,<\/span><a id=\"xref-corresp-1-2\" class=\"xref-corresp\" style=\"font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/content\/30\/22\/3143.full?etoc#corresp-1\">*<\/a><\/li>\n<\/ol>\n<p class=\"affiliation-list-reveal\" style=\"font-weight: inherit;font-style: inherit\"><a class=\"view-more\" style=\"font-weight: bold;font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/content\/30\/22\/3143.full?etoc#\">+<\/a>Author Affiliations<\/p>\n<ol class=\"affiliation-list hideaffil\" style=\"font-style: inherit\">\n<li class=\"aff\" style=\"font-weight: inherit;font-style: inherit\"><a id=\"aff-1\" style=\"font-style: inherit;color: #0000cc\" name=\"aff-1\"><\/a><br \/>\n<address style=\"font-weight: inherit\"><sup style=\"font-weight: inherit;font-style: inherit\">1<\/sup>IZKF Computational Biology Research Group, Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen,\u00a0<sup style=\"font-weight: inherit;font-style: inherit\">2<\/sup>Computational RNA Biology Lab and Bioinformatics Core, Max Planck Institute for Biology of Ageing, 50931 Cologne,\u00a0<sup style=\"font-weight: inherit;font-style: inherit\">3<\/sup>Department of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074,\u00a0<sup style=\"font-weight: inherit;font-style: inherit\">4<\/sup>Helmholtz Institute for Biomedical Engineering, 52074,\u00a0<sup style=\"font-weight: inherit;font-style: inherit\">5<\/sup>Aachen Institute for Advanced Study in Computational Engineering Science (AICES), RWTH Aachen University, 52062 Aachen, Germany and\u00a0<sup style=\"font-weight: inherit;font-style: inherit\">6<\/sup>Center of Informatics, Federal University of Pernambuco, 50740560 Recife-PE, Brazil<\/address>\n<\/li>\n<\/ol>\n<ol class=\"corresp-list\" style=\"font-weight: inherit;font-style: inherit\">\n<li id=\"corresp-1\" class=\"corresp\" style=\"font-weight: inherit;font-style: inherit\"><a class=\"rev-xref\" style=\"font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/content\/30\/22\/3143.full?etoc#xref-corresp-1-1\">\u21b5<\/a>*To whom correspondence should be addressed<\/li>\n<\/ol>\n<ul class=\"history-list\" style=\"font-weight: inherit;font-style: inherit\">\n<li class=\"received\" style=\"font-weight: inherit;font-style: inherit\"><span class=\"received-label\" style=\"font-weight: inherit;font-style: inherit\">Received\u00a0<\/span>October 28, 2013.<\/li>\n<li class=\"rev-recd\" style=\"font-weight: inherit;font-style: inherit\"><span class=\"rev-recd-label\" style=\"font-weight: inherit;font-style: inherit\">Revision received\u00a0<\/span>June 27, 2014.<\/li>\n<li class=\"accepted\" style=\"font-weight: inherit;font-style: inherit\"><span class=\"accepted-label\" style=\"font-weight: inherit;font-style: inherit\">Accepted\u00a0<\/span>July 25, 2014.<\/li>\n<\/ul>\n<\/div>\n<div id=\"abstract-1\" class=\"section abstract\" style=\"color: #000000\">\n<h2 style=\"font-weight: lighter;font-style: inherit;color: #49382a\">Abstract<\/h2>\n<p id=\"p-2\" style=\"font-weight: inherit;font-style: inherit\"><strong style=\"font-weight: bold;font-style: inherit\">Motivation:<\/strong>\u00a0The identification of active transcriptional regulatory elements is crucial to understand regulatory networks driving cellular processes such as cell development and the onset of diseases. It has recently been shown that chromatin structure information, such as DNase I hypersensitivity (DHS) or histone modifications, significantly improves cell-specific predictions of transcription factor binding sites. However, no method has so far successfully combined both DHS and histone modification data to perform active binding site prediction.<\/p>\n<p id=\"p-3\" style=\"font-weight: inherit;font-style: inherit\"><strong style=\"font-weight: bold;font-style: inherit\">Results:<\/strong>\u00a0We propose here a method based on hidden Markov models to integrate DHS and histone modifications occupancy for the detection of open chromatin regions and active binding sites. We have created a framework that includes treatment of genomic signals, model training and genome-wide application. In a comparative analysis, our method obtained a good trade-off between sensitivity versus specificity and superior area under the curve statistics than competing methods. Moreover, our technique does not require further training or sequence information to generate binding location predictions. Therefore, the method can be easily applied on new cell types and allow flexible downstream analysis such as<em style=\"font-weight: inherit;font-style: italic\">de novo<\/em>\u00a0motif finding.<\/p>\n<p id=\"p-4\" style=\"font-weight: inherit;font-style: inherit\"><strong style=\"font-weight: bold;font-style: inherit\">Availability and implementation:<\/strong>\u00a0Our framework is available as part of the Regulatory Genomics Toolbox. The software information and all benchmarking data are available at\u00a0<a style=\"font-weight: inherit;font-style: inherit;color: #0000cc\" href=\"http:\/\/costalab.org\/wp\/dh-hmm\">http:\/\/costalab.org\/wp\/dh-hmm<\/a>.<\/p>\n<p id=\"p-5\" style=\"font-weight: inherit;font-style: inherit\"><strong style=\"font-weight: bold;font-style: inherit\">Contact:<\/strong>\u00a0<a style=\"font-weight: inherit;font-style: inherit;color: #0000cc\" href=\"mailto:ivan.costa@rwth-aachen.de\">ivan.costa@rwth-aachen.de<\/a>\u00a0or\u00a0<a style=\"font-weight: inherit;font-style: inherit;color: #0000cc\" href=\"mailto:eduardo.gusmao@rwth-aachen.de\">eduardo.gusmao@rwth-aachen.de<\/a><\/p>\n<p id=\"p-6\" style=\"font-weight: inherit;font-style: inherit\"><strong style=\"font-weight: bold;font-style: inherit\">Supplementary information:<\/strong>\u00a0<a style=\"font-weight: inherit;font-style: inherit;color: #0000cc\" href=\"http:\/\/bioinformatics.oxfordjournals.org\/lookup\/suppl\/doi:10.1093\/bioinformatics\/btu519\/-\/DC1\">Supplementary data<\/a>\u00a0are available at<em style=\"font-weight: inherit;font-style: italic\">Bioinformatics<\/em>\u00a0online.<\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Detection of active transcription factor binding sites with the combination of DNase hypersensitivity and histone modifications Eduardo G. Gusmao1,*, Christoph Dieterich2, Martin Zenke3,4\u00a0and Ivan G. Costa1,5,6,* +Author Affiliations 1IZKF Computational Biology Research Group, Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen,\u00a02Computational RNA Biology Lab and Bioinformatics Core, Max Planck Institute for Biology [&hellip;]<\/p>\n","protected":false},"author":88,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[3,13],"tags":[69,70,71,4,31],"_links":{"self":[{"href":"https:\/\/blogs.discovery.wisc.edu\/sysbiojournalclub\/wp-json\/wp\/v2\/posts\/188"}],"collection":[{"href":"https:\/\/blogs.discovery.wisc.edu\/sysbiojournalclub\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.discovery.wisc.edu\/sysbiojournalclub\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.discovery.wisc.edu\/sysbiojournalclub\/wp-json\/wp\/v2\/users\/88"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.discovery.wisc.edu\/sysbiojournalclub\/wp-json\/wp\/v2\/comments?post=188"}],"version-history":[{"count":1,"href":"https:\/\/blogs.discovery.wisc.edu\/sysbiojournalclub\/wp-json\/wp\/v2\/posts\/188\/revisions"}],"predecessor-version":[{"id":189,"href":"https:\/\/blogs.discovery.wisc.edu\/sysbiojournalclub\/wp-json\/wp\/v2\/posts\/188\/revisions\/189"}],"wp:attachment":[{"href":"https:\/\/blogs.discovery.wisc.edu\/sysbiojournalclub\/wp-json\/wp\/v2\/media?parent=188"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.discovery.wisc.edu\/sysbiojournalclub\/wp-json\/wp\/v2\/categories?post=188"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.discovery.wisc.edu\/sysbiojournalclub\/wp-json\/wp\/v2\/tags?post=188"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}