PMID- 29213263 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231112 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 8 DP - 2017 TI - Scoring Targets of Transcription in Bacteria Rather than Focusing on Individual Binding Sites. PG - 2314 LID - 10.3389/fmicb.2017.02314 [doi] LID - 2314 AB - Reliable identification of targets of bacterial regulators is necessary to understand bacterial gene expression regulation. These targets are commonly predicted by searching for high-scoring binding sites in the upstream genomic regions, which typically leads to a large number of false positives. In contrast to the common approach, here we propose a novel concept, where overrepresentation of the scoring distribution that corresponds to the entire searched region is assessed, as opposed to predicting individual binding sites. We explore two implementations of this concept, based on Kolmogorov-Smirnov (KS) and Anderson-Darling (AD) tests, which both provide straightforward P-value estimates for predicted targets. This approach is implemented for pleiotropic bacterial regulators, including sigma(70) (bacterial housekeeping sigma factor) target predictions, which is a classical bioinformatics problem characterized by low specificity. We show that KS based approach is both faster and more accurate, departing from the current paradigm of AD being slower, but more accurate. Moreover, KS approach leads to a significant increase in the search accuracy compared to the standard approach, while at the same time straightforwardly assigning well established P-values to each potential target. Consequently, the new KS based method proposed here, which assigns P-values to fixed length upstream regions, provides a fast and accurate approach for predicting bacterial transcription targets. FAU - Djordjevic, Marko AU - Djordjevic M AD - Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Belgrade, Serbia. FAU - Djordjevic, Magdalena AU - Djordjevic M AD - Institute of Physics Belgrade, University of Belgrade, Belgrade, Serbia. FAU - Zdobnov, Evgeny AU - Zdobnov E AD - Swiss Institute of Bioinformatics and Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland. LA - eng PT - Journal Article DEP - 20171122 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC5702782 OTO - NOTNLM OT - bacterial gene expression regulation OT - direct target gene predictions OT - position specific weight matrices OT - sigma70 OT - transcription factor binding site predictions OT - transcription regulation OT - transcription start starts OT - transcription targets EDAT- 2017/12/08 06:00 MHDA- 2017/12/08 06:01 PMCR- 2017/11/22 CRDT- 2017/12/08 06:00 PHST- 2017/07/31 00:00 [received] PHST- 2017/11/09 00:00 [accepted] PHST- 2017/12/08 06:00 [entrez] PHST- 2017/12/08 06:00 [pubmed] PHST- 2017/12/08 06:01 [medline] PHST- 2017/11/22 00:00 [pmc-release] AID - 10.3389/fmicb.2017.02314 [doi] PST - epublish SO - Front Microbiol. 2017 Nov 22;8:2314. doi: 10.3389/fmicb.2017.02314. eCollection 2017.