Conclusion
We have used PhyloScan to combine evidence from matching sites found in orthologous data from several related bacterial species. In simulated sequence data, we demonstrate good sensitivity at high specificity levels. In real sequence data we are able to rediscover many of the known Crp and PurR transcription factor binding sites in E. coli, and we predict several novel Crp-significant intergenic regions and several novel PurR-significant intergenic regions in E. coli; specifically, over half of the Crp sites and one-third of the PurR sites are not experimentally validated by DNase I or electrophoretic mobility shift assays. Accordingly, our results have provided several new potential binding sites for these transcription factors, that require validation, to enable further delineation of these regulons in E. coli.
Through its capability of using cross-species data, PhyloScan improves the sensitivity of motif scanning; because the approach permits the use of both aligned and unaligned data, from both evolutionarily near and somewhat more distant species, it is our hope that researchers will find it useful in a wide variety of settings.
PhyloScan is available on request from the authors via phyloscan@wadsworth.org, and a Web interface for the software is available [37].