CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes

<p>Abstract</p> <p>Background</p> <p>The identification of transcription factor binding sites is difficult since they are only a small number of nucleotides in size, resulting in large numbers of false positives and false negatives in current approaches. Computational m...

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Bibliographic Details
Main Authors: den Dunnen Johan T, van Ommen Gert-Jan B, Villerius Michel P, van Galen Michiel, Hestand Matthew S, 't Hoen Peter AC
Format: Article
Language:English
Published: BMC 2008-11-01
Series:BMC Bioinformatics
Online Access:http://www.biomedcentral.com/1471-2105/9/495
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Summary:<p>Abstract</p> <p>Background</p> <p>The identification of transcription factor binding sites is difficult since they are only a small number of nucleotides in size, resulting in large numbers of false positives and false negatives in current approaches. 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.</p> <p>Results</p> <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<sup><it>R </it></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.</p> <p>Conclusion</p> <p>The program CORE_TF is accessible in a user friendly web interface at <url>http://www.LGTC.nl/CORE_TF</url>. 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.</p>
ISSN:1471-2105