RegPredict: an integrated system for regulon inference in prokaryotes by comparative genomics approach

Abstract

RegPredict web server is designed to provide comparative genomics tools for reconstruction and analysis of microbial regulons using comparative genomics approach. The server allows the user to rapidly generate reference sets of regulons and regulatory motif profiles in a group of prokaryotic genomes. The new concept of a cluster of co-regulated orthologous operons allows the user to distribute the analysis of large regulons and to perform the comparative analysis of multiple clusters independently. Two major workflows currently implemented in RegPredict are: (i) regulon reconstruction for a known regulatory motif and (ii) ab initio inference of a novel regulon using several scenarios for the generation of starting gene sets. RegPredict provides a comprehensive collection of manually curated positional weight matrices of regulatory motifs. It is based on genomic sequences, ortholog and operon predictions from the MicrobesOnline. An interactive web interface of RegPredict integrates and presents diverse genomic and functional information about the candidate regulon members from several web resources. RegPredict is freely accessible at http://regpredict.lbl.gov.

Antiparallel and Interlinked Control of Cellular Iron Levels by the Irr and RirA Regulators of Agrobacterium tumefaciens

“…Consensus DNA binding sites for Irr (the iron control element [ICE] box) and RirA (the iron response operator [IRO] box) have been determined for the Alphaproteobacteria (53). The presence of ICE and IRO boxes in the genome of A. tumefaciens was analyzed using the RegPredict software package with score cutoffs of 4.9 for ICE box prediction and 3.93 for IRO box prediction (45). The positional weight matrices for the ICE and IRO sequences were previously established by D. A. Rodionov (personal communication).…”

Inference of the Transcriptional Regulatory Network in Staphylococcus aureus by Integration of Experimental and Genomics-Based Evidence

“…Two major components of this analysis are (i) the propagation of previously known regulons from model organisms (e.g., S. aureus and Bacillus subtilis) to others and (ii) the ab initio prediction of novel regulons. Here we used these two regulon reconstruction workflows implemented in the RegPredict Web server (http://regpredict.lbl.gov/) (30). Initially, the training set of regulatory regions containing either known or as-yet-unknown TFBSs was collected and used as an input for a suite of tools for regulatory motif identification and regulon reconstruction in microbial genomes.…”

Guide to Genome-Wide Bacterial Transcription Factor Binding Site Prediction Using OmpR as Model

“…More advanced pattern matching programs incorporate the use of cross-species conservations during their genome search to enrich the predicted sites. Comparative genomics approach is predicated on the idea that TFs from related organisms regulate genes that tend to be conserved (Novichkov et al, 2010b). Presence of similar TFBSs upstream of orthologous genes increases the probability that the sites are functional binding sites (Novichkov et al, 2010b).…”

“…Comparative genomics approach is predicated on the idea that TFs from related organisms regulate genes that tend to be conserved (Novichkov et al, 2010b). Presence of similar TFBSs upstream of orthologous genes increases the probability that the sites are functional binding sites (Novichkov et al, 2010b). PhyloScan (Carmack et al, 2007;Palumbo & Newberg, 2010) is a web program that screens candidate sequences by using (1) aligned or unaligned sequence data from multiple species, even evolutionarily distant ones, (2) multiple sites within an intergenic region, and (3) qvalues to predict more functional TFBSs, even weak ones, in a genome.…”

“…The use of q-values is in contrast to conventional motif matching programs, which either score a candidate binding site against a training set of TFBS or evaluate the statistical significance of the candidate binding site using p-value. Another program that takes the comparative genomics approach is RegPredict (Novichkov et al, 2010b), a web site that provides a visual environment for the discovery of genes regulated by a TF in prokaryotes. The site contains a large collection of known TFBS motifs gathered from the RegPrecise, RegTransBase, and RegulonDB databases and genomic sequences of major taxonomic groups of Bacteria.…”