Modulefinder: a tool for computational discovery of cis regulatory modules

Regulation of gene expression occurs largely through the binding of sequence-specific transcription factors (TFs) to genomic binding sites (BSs). We present a rigorous scoring scheme, implemented as a C program termed "ModuleFinder", that evaluates the likelihood that a given genomic region is a cis regulatory module (CRM) for an input set of TFs according to its degree of: (1) homotypic site clustering; (2) heterotypic site clustering; and (3) evolutionary conservation across multiple genomes. Importantly, ModuleFinder obtains all parameters needed to appropriately weight the relative contributions of these sequence features directly from the input sequences and TFBS motifs, and does not need to first be trained. Using two previously described collections of experimentally verified CRMs in mammals and in fly as validation datasets, we show that ModuleFinder is able to identify CRMs with great sensitivity and specificity.