Integrating sequence analysis with biophysical modelling for accurate transcription start site prediction

Promoter prediction in bacteria is a classical bioinformatics problem, where available methods for regulatory element detection exhibit a very high number of false positives. We here argue that accurate transcription start site (TSS) prediction is a complex problem, where available methods for sequence motif discovery are not in itself well adopted for solving the problem. We here instead propose that the problem requires integration of quantitative understanding of transcription initiation with careful description of promoter sequence specificity. We review evidence for this viewpoint, and discuss a current progress on these issues on the example of sigma70 transcription start sites in E. coli.