CONFAC: automated application of comparative genomic promoter analysis to DNA microarray datasets
1 Program in Bioinformatics, School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA and 2 Department of Pathology and Laboratory Medicine and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
* To whom correspondence should be addressed at Whitehead Biomedical Research Building, Room 105A, 615 Michael St., Atlanta, GA 30322, USA. Tel: +1 404 712 2809; Fax: +1 404 727 8538; Email: cmoreno{at}emory.edu
Received January 29, 2004; Revised and Accepted February 23, 2004
The advent of DNA microarray technology and the sequencing of multiple vertebrate genomes has provided a unique opportunity for the integration of comparative genomics with high-throughput gene expression analysis. Here we describe the conserved transcription factor binding site (CONFAC) software that enables the high-throughput identification of conserved transcription factor binding sites (TFBSs) in the regulatory regions of hundreds of genes at a time (http://morenolab.whitehead.emory.edu/cgi-bin/confac/login.pl). The CONFAC software compares non-coding regulatory sequences between human and mouse genomes to enable identification of conserved TFBSs that are significantly enriched in promoters of gene clusters from microarray analyses compared to sets of unchanging control genes using a Mann–Whitney U-test. Analysis of random gene sets demonstrated that using our approach, over 98% of TFBSs had false positive rates below 5%. As a proof-of-principle, we have validated the CONFAC software using gene sets from four separate microarray studies and identified TFBSs known to be functionally important for regulation of each of the four gene sets.
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