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Bioinformatics Advance Access published online on December 6, 2005
Bioinformatics, doi:10.1093/bioinformatics/bti819
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© The Author (2005). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received September 27, 2005
Revised November 30, 2005
Accepted December 2, 2005

Article

Evaluating phylogenetic footprinting for human-rodent comparisons

Tilman Sauer 1 *, Ekaterina Shelest 1, and Edgar Wingender 2

1 Department of Bioinformatics, UKG, Georg-August-University of Goettingen, Goldschmidtstr. 1, 37077 Goettingen, Germany
2 Department of Bioinformatics, UKG, Georg-August-University of Goettingen, Goldschmidtstr. 1, 37077 Goettingen, Germany; BIOBASE GmbH, Halchtersche Str. 33, 38304 Wolfenbuettel, Germany

* To whom correspondence should be addressed.
Tilman Sauer, E-mail: tsa{at}bioinf.med.uni-goettingen.de


  Abstract

Motivation: "Phylogenetic Footprinting" is a widely applied approach to identify regulatory regions and potential transcription factor binding sites (TFBSs) using alignments of non-coding orthologous regions from two or more organisms. A systematic evaluation of its validity and usability based on known TFBSs is needed to use phylogenetic footprinting most effectively in the identification of unknown TFBSs.

Results: In this paper we use 2678 human, mouse and rat TFBSs from the TRANSFAC® database for this evaluation. To ensure the retrieval of correct orthologous sequences, we combine gene annotation and sequence homology searches. Demanding a sequence identity of at least 65% is most effective in discriminating TFBSs from non-functional sequence parts, while different alignment algorithms only have a minor influence on TFBS identification by human-rodent comparisons. With this threshold about 72% of the known TFBSs are found conserved, a number which varies significantly between different transcription factors and also depends on the function of the regulated gene. TFBSs for certain transcription factors do not require strict sequence conservation but instead may show a high pattern conservation, limiting somewhat the validity of purely sequence-based phylogenetic footprinting.

Availability: Scripts are available from the authors upon request.


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