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Nucleic Acids Research Advance Access published online on December 18, 2006
Nucleic Acids Research, doi:10.1093/nar/gkl1011
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© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Database Issue

GenomeTrafac: a whole genome resource for the detection of transcription factor binding site clusters associated with conventional and microRNA encoding genes conserved between mouse and human gene orthologs

Anil G. Jegga1,2, Jing Chen1,3, Sivakumar Gowrisankar1,3, Mrunal A. Deshmukh1, RangaChandra Gudivada1,3, Sue Kong1, Vivek Kaimal1,3 and Bruce J. Aronow1,2,3,*

1 Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center Cincinnati, OH 45229, USA 2 Department of Pediatrics, College of Medicine Cincinnati, OH 45229, USA 3 Department of Biomedical Engineering, University of Cincinnati Cincinnati, OH 45229, USA

*To whom correspondence should be addressed at Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue–MLC 7024, Cincinnati, OH 45229-3039, USA. Tel: +1 513 636 4865; Fax: +1 513 636 2056; Email: bruce.aronow{at}cchmc.org

Received August 16, 2006. Revised November 1, 2006. Accepted November 1, 2006.

Transcriptional cis-regulatory control regions frequently are found within non-coding DNA segments conserved across multi-species gene orthologs. Adopting a systematic gene-centric pipeline approach, we report here the development of a web-accessible database resource—GenomeTraFac (http://genometrafac.cchmc.org)—that allows genome-wide detection and characterization of compositionally similar cis-clusters that occur in gene orthologs between any two genomes for both microRNA genes as well as conventional RNA-encoding genes. Each ortholog gene pair can be scanned to visualize overall conserved sequence regions, and within these, the relative density of conserved cis-element motif clusters form graph peak structures. The results of these analyses can be mined en masse to identify most frequently represented cis-motifs in a list of genes. The system also provides a method for rapid evaluation and visualization of gene model-consistency between orthologs, and facilitates consideration of the potential impact of sequence variation in conserved non-coding regions to impact complex cis-element structures. Using the mouse and human genomes via the NCBI Reference Sequence database and the Sanger Institute miRBase, the system demonstrated the ability to identify validated transcription factor targets within promoter and distal genomic regulatory regions of both conventional and microRNA genes.


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