A biophysical approach to transcription factor binding site discovery.

@article{citeulike:876590, abstract = {Identification of transcription factor binding sites within regulatory segments of genomic DNA is an important step toward understanding of the regulatory circuits that control expression of genes. Here, we describe a novel bioinformatics method that bases classification of potential binding sites explicitly on the estimate of sequence-specific binding energy of a given transcription factor. The method also estimates the chemical potential of the factor that defines the threshold of binding. In contrast with the widely used information-theoretic weight matrix method, the new approach correctly describes saturation in the transcription factor/DNA binding probability. This results in a significant improvement in the number of expected false positives, particularly in the ubiquitous case of low-specificity factors. In the strong binding limit, the algorithm is related to the "support vector machine" approach to pattern recognition. The new method is used to identify likely genomic binding sites for the E. coli transcription factors collected in the DPInteract database. In addition, for CRP (a global regulatory factor), the likely regulatory modality (i.e., repressor or activator) of predicted binding sites is determined.}, address = {Department of Physics, Columbia University, New York, New York 10025, USA.}, author = {Djordjevic, M. and Sengupta, A. M. and Shraiman, B. I. }, citeulike-article-id = {876590}, doi = {http://dx.doi.org/10.1101/gr.1271603}, issn = {1088-9051}, journal = {Genome Res}, keywords = {affinity}, month = {November}, number = {11}, pages = {2381--2390}, posted-at = {2008-07-10 02:59:48}, priority = {2}, title = {A biophysical approach to transcription factor binding site discovery.}, url = {http://dx.doi.org/10.1101/gr.1271603}, volume = {13}, year = {2003} }

TY - JOUR ID - citeulike:876590 L3 - citeulike-article-id:876590 TI - A biophysical approach to transcription factor binding site discovery. JF - Genome Res VL - 13 IS - 11 SP - 2381 EP - 2390 AD - Department of Physics, Columbia University, New York, New York 10025, USA. SN - 1088-9051 N2 - Identification of transcription factor binding sites within regulatory segments of genomic DNA is an important step toward understanding of the regulatory circuits that control expression of genes. Here, we describe a novel bioinformatics method that bases classification of potential binding sites explicitly on the estimate of sequence-specific binding energy of a given transcription factor. The method also estimates the chemical potential of the factor that defines the threshold of binding. In contrast with the widely used information-theoretic weight matrix method, the new approach correctly describes saturation in the transcription factor/DNA binding probability. This results in a significant improvement in the number of expected false positives, particularly in the ubiquitous case of low-specificity factors. In the strong binding limit, the algorithm is related to the "support vector machine" approach to pattern recognition. The new method is used to identify likely genomic binding sites for the E. coli transcription factors collected in the DPInteract database. In addition, for CRP (a global regulatory factor), the likely regulatory modality (i.e., repressor or activator) of predicted binding sites is determined. KW - affinity AU - Djordjevic, M AU - Sengupta, AM AU - Shraiman, BI PY - 2003/11// UR - http://dx.doi.org/10.1101/gr.1271603 ER -