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Bioinformatics Advance Access published online on November 10, 2006
Bioinformatics, doi:10.1093/bioinformatics/btl565
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© 2006 The Author(s)
Received October 1, 2006
Revised November 6, 2006
Accepted November 6, 2006

Article

Predicting transcription factor affinities to DNA from a biophysical model

Helge Roider 1, Aditi Kanhere 1, Thomas Manke 1, and Martin Vingron 1 *

1 Max-Planck-Institute for Molecular Genetics, Ihnestr. 73, 14195 Berlin, Germany

* To whom correspondence should be addressed.
Martin Vingron, E-mail: vingron{at}molgen.mpg.de


  Abstract

Motivation: Theoretical efforts to understand the regulation of gene expression are traditionally centered around the identification of transcription factor binding sites at specific DNA positions. More recently these efforts have been supplemented by experimental data for relative binding affinities of proteins to longer intergenic sequences. The question arises to what extent these two approaches converge. In this paper we adopt a physical binding model to predict the relative binding affinity of a transcription factor for a given sequence.

Results: We find that a significant fraction of genome-wide binding data in yeast can be accounted for by simple count matrices and a physical model with only two parameters. We demonstrate that our approach is both conceptually and practically more powerful than traditional methods which require selection of a cutoff. Our analysis yields biologically meaningful parameters, suitable for predicting relative binding affinities in the absence of experimental binding data.

Availability: The C source code for our TRAP program is freely available for non-commercial use at http://www.molgen.mpg.de/~manke/papers/TFaffinities/.

Associate Editor: Chris Stoeckert
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