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


CONCLUSIONS
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.
Hestand
Matthew S
MS
The 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
van Galen
Michiel
M
Villerius
Michel P
MP
van Ommen
Gert-Jan B
GJ
den Dunnen
Johan T
JT
't Hoen
Peter A C
PA
D000465:Algorithms; D000818:Animals; D001185:Artificial Intelligence; D001482:Base Composition; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D030541:Databases, Genetic; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D020407:Internet; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment / Q000379:methods*; D012984:Software; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014584:User-Computer Interface
D014157:Transcription Factors