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BMC Bioinformatics. 2008 Nov 26;9:495. doi: 10.1186/1471-2105-9-495.

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

Author information

  • 1The Center for Human and Clinical Genetics, Leiden University Medical Center, Postzone S4-0P, PO Box 9600, 2300 RC Leiden, The Netherlands. M.S.Hestand@lumc.nl

Abstract

BACKGROUND:

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.

RESULTS:

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 R 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.

CONCLUSION:

The program CORE_TF is accessible in a user friendly web interface at http://www.LGTC.nl/CORE_TF. 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.

PMID:
19036135
[PubMed - indexed for MEDLINE]
PMCID:
PMC2613159
Free PMC Article
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