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. 2010 Jul;38(Web Server issue):W299-307.
doi: 10.1093/nar/gkq531. Epub 2010 Jun 11.

RegPredict: An Integrated System for Regulon Inference in Prokaryotes by Comparative Genomics Approach

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Free PMC article

RegPredict: An Integrated System for Regulon Inference in Prokaryotes by Comparative Genomics Approach

Pavel S Novichkov et al. Nucleic Acids Res. .
Free PMC article

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.

Figures

Figure 1.
Figure 1.
Major steps in building Clusters of co-Regulated Orthologous operoNs (CRONs): (A) search for putative TF binding sites, (B) building a core of a CRON, (C) extension of the core to form a final CRON. Three genomes are represented by straight lines. Putative operons are shown by rectangles. Genes are shown by colored arrows. The orthologous genes are depicted by the same color. Genes marked by light gray color do not have orthologs in other two genomes. Red circles depict the putative TFBSs. A core of a CRON is constructed as a set of operons containing orthologous genes preceded by putative TFBSs (highlighted by pink background). A final CRON is expanded by inclusion of orthologous genes without putative TFBSs (highlighted by light blue background).
Figure 2.
Figure 2.
Diagram of regulon inference workflows implemented in the RegPredict web server. (I) regulon reconstruction for known regulatory motif profile, (II) ab initio regulon inference when a regulatory motif is not known.
Figure 3.
Figure 3.
The parts of interface devoted to user input in two main strategies of regulon inference. (A) ‘Run Profile’ allows the user to start regulon reconstruction for a known PWM profile, (B) ‘Discover Profiles’ initiates the procedure for inferring candidate motifs in a training set of sequences.
Figure 4.
Figure 4.
Interactive workspace of the RegPredict web server. Example shows the main output obtained by scanning nine Shewanella genomes with PWM for the NagR transcription factor. Prioritized clusters of co-regulated orthologous operons (CRONs) are listed in the left panel table. Genomic context and summary gene function information for the first selected CRON are shown in the central and right panels, respectively. Detailed genomic information for the selected NagR-regulated operon in S. oneidensis MR-1 is shown in the bottom panel.

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