Abstract
BackgroundThe application of DNA microarray technology in post-genomic analysis of bacterial genome sequences has allowed the generation of huge amounts of data related to regulatory networks. This data along with literature-derived knowledge on regulation of gene expression has opened the way for genome-wide reconstruction of transcriptional regulatory networks. These large-scale reconstructions can be converted into in silico models of bacterial cells that allow a systematic analysis of network behavior in response to changing environmental conditions.DescriptionCoryneRegNet was designed to facilitate the genome-wide reconstruction of transcriptional regulatory networks of corynebacteria relevant in biotechnology and human medicine. During the import and integration process of data derived from experimental studies or literature knowledge CoryneRegNet generates links to genome annotations, to identified transcription factors and to the corresponding cis-regulatory elements. CoryneRegNet is based on a multi-layered, hierarchical and modular concept of transcriptional regulation and was implemented by using the relational database management system MySQL and an ontology-based data structure. Reconstructed regulatory networks can be visualized by using the yFiles JAVA graph library. As an application example of CoryneRegNet, we have reconstructed the global transcriptional regulation of a cellular module involved in SOS and stress response of corynebacteria.ConclusionCoryneRegNet is an ontology-based data warehouse that allows a pertinent data management of regulatory interactions along with the genome-scale reconstruction of transcriptional regulatory networks. These models can further be combined with metabolic networks to build integrated models of cellular function including both metabolism and its transcriptional regulation.
Highlights
The application of DNA microarray technology in post-genomic analysis of bacterial genome sequences has allowed the generation of huge amounts of data related to regulatory networks
The CoryneRegNet database discloses detailed information on DNA-binding transcription factors, the key players in regulation of gene expression, and on transcriptional regulatory interactions of C. glutamicum deduced from literature-derived knowledge, computer predictions and global DNA microarray hybridization experiments
CoryneRegNet was developed as a data warehouse of transcriptional regulatory networks of C. glutamicum, its ontology-based design along with its programs and scripts is generally applicable to implement other species-specific databases
Summary
With the recent progress made in large-scale postgenomic analysis of complete genome sequences a vast amount of novel data is becoming available. A web-based user interface provides access to the database content, allows various queries and supports the reconstruction and visualization of regulatory networks at different hierarchical levels. CoryneRegNet was developed as a data warehouse of transcriptional regulatory networks of C. glutamicum, its ontology-based design along with its programs and scripts is generally applicable to implement other species-specific databases. CoryneRegNet is a versatile systems biology tool to support the large-scale analysis of transcriptional regulation of gene expression in microorganisms. Since comparative computer analyses exploiting transcriptional regulatory data might be helpful to uncover hidden information on regulation of gene expression, transcriptional data of other sequenced corynebacterial species will be integrated into the release of CoryneRegNet. For the future, we further plan to integrate existing and currently developing bioinformatics tools to perform for instance genome-wide searches for regulatory motifs specified by position weight matrices with sound statistical analysis [38] or to discover new potential motifs based on transcriptional profile analysis and comparative sequence analysis over several related genomes.
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