A simple hyper-geometric approach for discovering putative transcription factor binding sites

A central issue in molecular biology is understanding the regulatory mechanisms that control gene expression. The recent flood of genomic and postgenomic data opens the way for computational methods elucidating the key components that play a role in these mechanisms. One important consequence is the ability to recognize groups of genes that are co-expressed using microarray expression data. We then wish to identify in-silico putative transcription factor binding sites in the promoter regions of these gene, that might explain the coregulation, and hint at possible regulators. In this paper we describe a simple and fast, yet powerful, two stages approach to this task. Using a rigorous hypergeometric statistical analysis and a straightforward computational procedure we find small conserved sequence kernels. These are then stochastically expanded into PSSMs using an EM-like procedure. We demonstrate the utility and speed of our methods by applying them to several data sets from recent literature. We also compare these results with those of MEME when run on the same sets.