Deciphering the cis-regulatory code hidden within genome sequences is a formidable challenge for the post-genomic era. In the Early Edition of the Proceedings of the National Academy of Sciences, Mark Rebeiz and colleagues report the creation of a computational method for identifying potential cis-regulatory modules and target genes (Proc Natl Acad Sci USA 2002, 10.1073/pnas.152320899).

Their algorithm, called SCORE (Site Clustering Over Random Expectation), evaluates statistically significant enrichment for clusters of binding sites of a particular transcription factor within genome sequence. Rebeiz et al. validated this approach by looking for enhancers regulated by Suppressor of Hairless [Su(H)], a component of the Notch signaling pathway in Drosophila.

They found over 15,000 potential Su(H)-binding sites in the Drosophila genome and used the well-known observation that bona fide binding sites are often clustered to identify potentially significant binding sites, within clusters. Many of these clusters fall near genes...