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Computational methods to reduce false positives are to look for over-representation of transcription factor binding sites in a set of similarly regulated promoters or to look for conservation in orthologous promoter alignments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We have developed a novel tool, \"CORE_TF\" (Conserved and Over-REpresented Transcription Factor binding sites) that identifies common transcription factor binding sites in promoters of co-regulated genes. To improve upon existing binding site predictions, the tool searches for position weight matrices from the TRANSFAC<jats:sup><jats:italic>R<\/jats:italic><\/jats:sup>database that are over-represented in an experimental set compared to a random set of promoters and identifies cross-species conservation of the predicted transcription factor binding sites. The algorithm has been evaluated with expression and chromatin-immunoprecipitation on microarray data. We also implement and demonstrate the importance of matching the random set of promoters to the experimental promoters by GC content, which is a unique feature of our tool.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The program CORE_TF is accessible in a user friendly web interface at<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.LGTC.nl\/CORE_TF\" ext-link-type=\"uri\">http:\/\/www.LGTC.nl\/CORE_TF<\/jats:ext-link>. It provides a table of over-represented transcription factor binding sites in the users input genes' promoters and a graphical view of evolutionary conserved transcription factor binding sites. In our test data sets it successfully predicts target transcription factors and their binding sites.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2105-9-495","type":"journal-article","created":{"date-parts":[[2008,11,26]],"date-time":"2008-11-26T19:13:35Z","timestamp":1227726815000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes"],"prefix":"10.1186","volume":"9","author":[{"given":"Matthew S","family":"Hestand","sequence":"first","affiliation":[]},{"given":"Michiel","family":"van Galen","sequence":"additional","affiliation":[]},{"given":"Michel P","family":"Villerius","sequence":"additional","affiliation":[]},{"given":"Gert-Jan B","family":"van Ommen","sequence":"additional","affiliation":[]},{"given":"Johan T","family":"den Dunnen","sequence":"additional","affiliation":[]},{"given":"Peter AC","family":"'t Hoen","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2008,11,26]]},"reference":[{"issue":"3","key":"2480_CR1","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1093\/bib\/5.3.217","volume":"5","author":"G Pavesi","year":"2004","unstructured":"Pavesi G, Mauri G, Pesole G: In silico representation and discovery of transcription factor binding sites. 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