Co-regulation is a basic mechanism to coordinately control expression of genes in modules, biochemical pathways and protein complexes (1) (2) (3) . In eukaryotes, expression is most often mediated by transcription factors (TFs) that bind upstream of the transcription start site (TSS) and recruit the polymerase assembly (4) . TFs bind, with varying affinity, to a set of similar, short (6-20 nt) sequences (5) . Computational binding site discovery focuses on finding significantly overrepresented sequences in upstream regions of co-regulated genes (6) (7) (8) . Thus, computational TFBS prediction algorithms must begin with an input set of promoters from genes hypothetically co-regulated by a shared TF. The algorithms aim to predict the binding positions and consequently the nucleotide specificity of the TF (9) (10) (11) .