A new framework for identifying cis-regulatory motifs in prokaryotes

We present a new algorithm, BOBRO, for prediction of cis-regulatory motifs in a given set of promoter sequences. The algorithm substantially improves the prediction accuracy and extends the scope of applicability of the existing programs based on two key new ideas: (i) we developed a highly effective method for reliably assessing the possibility for each position in a given promoter to be the (approximate) start of a conserved sequence motif; and (ii) we developed a highly reliable way for recognition of actual motifs from the accidental ones based on the concept of ‘motif closure’. These two key ideas are embedded in a classical framework for motif finding through finding cliques in a graph but have made this framework substantially more sensitive as well as more selective in motif finding in a very noisy background. A comparative analysis shows that the performance coefficient was improved from 29% to 41% by our program compared to the best among other six state-of-the-art prediction tools on a large-scale data sets of promoters from one genome, and also consistently improved by substantial margins on another kind of large-scale data sets of orthologous promoters across multiple genomes. The power of BOBRO in dealing with noisy data was further demonstrated through identification of the motifs of the global transcriptional regulators by running it over 2390 promoter sequences of Escherichia coli K12.