November 30, 2007

B2 NCBI Library

11AM

 

Leelavati Narlikar, Department of Computer Science, Duke University

 

Deciphering the transcriptional regulatory code using informative priors

 

Identifying transcription factor (TF) binding sites across the genome is 

an important problem in molecular biology. Large-scale discovery of TF 

binding sites is usually carried out by searching for short DNA patterns 

that appear often within promoter regions of genes that are known to be 

co-bound by a TF. In such problems, promoters have traditionally been 

treated as strings of nucleotide bases in which TF binding sites are 

assumed to be equally likely to occur at any position. In vivo, however, 

TFs localize to DNA binding sites as part of a complex thermodynamic 

process of cooperativity and competition, both with one another and, 

importantly, with DNA packaging proteins called nucleosomes. In 

particular, TFs are more likely to bind DNA at sites that are not occupied 

by nucleosomes.  In this talk, I shall demonstrate that it is possible to 

incorporate knowledge of the nucleosome landscape across the genome to aid 

binding site discovery; indeed, our Gibbs sampling-based algorithm 

incorporating nucleosome occupancy information is significantly more 

accurate than conventional methods [1].

 

If time permits, I shall talk about other sources of information like the 

structural class of the DNA-binding domain of the TF [2] and sequence 

conservation across multiple species [3] that we have successfully 

incorporated into our framework.

 

References:

 

[1] Narlikar, L., Gordan, R., and Hartemink, A. (2007) A Nucleosome-Guided 

Map of Transcription Factor Binding Sites in Yeast. PLoS Computational 

Biology, (accepted, in press).

 

[2] Narlikar, L., Gordan, R., Ohler, U., and Hartemink, A. (2006) 

Informative Priors Based on Transcription Factor Structural Class Improve 

de novo Motif Discovery. Intelligent Systems in Molecular Biology 2006 

(ISMB06), Bioinformatics, 22, July 2006. pp. e384--e392.

 

[3] Gordan, R., Narlikar, L., and Hartemink, A. (2007) A fast, 

alignment-free, conservation-based method for transcription factor binding 

site discovery (under review).