Nucleic Acids Research Advance Access published online on April 9, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn140
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Methods Online |
Detecting cis-regulatory binding sites for cooperatively binding proteins
1Department of Electrical Engineering, ESAT-SCD, Katholieke Universiteit Leuven, Kasteelpark Arenberg 10, 3001 Leuven, 2Department of Molecular and Cellular Interactions, VIB, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussel and 3Department of Electrical Engineering, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussel, Belgium
*To whom correspondence should be addressed. Tel: +32 16 328646; Email: Liesbeth.vanOeffelen{at}esat.kuleuven.be
Received January 15, 2008. Revised March 8, 2008. Accepted March 14, 2008.
Several methods are available to predict cis-regulatory modules in DNA based on position weight matrices. However, the performance of these methods generally depends on a number of additional parameters that cannot be derived from sequences and are difficult to estimate because they have no physical meaning. As the best way to detect cis-regulatory modules is the way in which the proteins recognize them, we developed a new scoring method that utilizes the underlying physical binding model. This method requires no additional parameter to account for multiple binding sites; and the only necessary parameters to model homotypic cooperative interactions are the distances between adjacent protein binding sites in basepairs, and the corresponding cooperative binding constants. The heterotypic cooperative binding model requires one more parameter per cooperatively binding protein, which is the concentration multiplied by the partition function of this protein. In a case study on the bacterial ferric uptake regulator, we show that our scoring method for homotypic cooperatively binding proteins significantly outperforms other PWM-based methods where biophysical cooperativity is not taken into account.