Category Cross-Omics>Knowledge Bases/Databases/Tools and Genomics>Gene Expression Analysis/Profiling/Tools

Abstract CoryneRegNet (Database of Corynebacterial Transcription Factors and Regulatory Networks) is a comprehensive system for the integrated analysis of prokaryotic Gene Regulatory Networks (GRNs).

It is a versatile systems biology platform to support the efficient and large- scale analysis of transcriptional regulation of ‘gene expression’ in microorganisms.

Starting with release 4.0 of CoryneRegNet, the database contains information on DNA-binding transcription factors and on transcriptional regulatory interactions of corynebacteria, mycobacteria and E. coli. The results of global ‘DNA microarray’ hybridization experiments have been integrated as Stimulons into the CoryneRegNet data repository.

Stimulons (imported from the database, or uploaded by the user) can be analyzed in the context of known ‘transcriptional regulatory networks’ to predict putative contradictions or further gene regulatory interactions.

Note: In cell biology a Stimulon is a collection of genes (which may be in operons and regulons) under regulation by the same stimulus. This term is generally used for prokaryotic systems, for example ‘quorum sensing’ in bacteria.

A web-based user interface provides access to the database content, allows various queries and supports the reconstruction, visualization, validation, and prediction of ‘regulatory networks’ at different hierarchical levels.

CoryneRegNet is linked to several databases [EMMA (DNA microarray analysis platform), GenDB (GenDB is a genome annotation system for prokaryotic genomes), COG (Clusters of Orthologous Groups of proteins), Gene Ontology (GO), National Center for Biotechnology Information (NCBI), etc.].

Although CoryneRegNet initially was developed as a data warehouse of transcriptional regulatory networks of C. glutamicum, its ontology-based design along with its programs and scripts has been designed for a general applicability to other species.

Hence, it has been extended with genomic and transcriptional data on 6 more organisms, experimental results (Stimulons) and computer predictions (protein clusters, Positional Weight Matrix (PWM)-based binding motif predictions, etc.).

CoryneRegNet is connected to other data sources using Web Services and provides its own Web Service for external consumers. Consequently, CoryneRegNet 4.0 is a versatile systems biology platform to support the efficient and large-scale analysis of transcriptional regulation of gene expression in microorganisms.

CoryneRegNet has been improved to provide the following updated database content and analysis features:

1) Integrated Web Service clients for GenDB and EMMA provide further gene annotation data and Stimulon (microarray) data respectively.

2) A publicly available Web Service server offers methods to other bioinformatics applications to query data from CoryneRegNet.

3) Protein clusters are integrated by using the ‘heuristic cluster editing’ software FORCE.

4) Integration of corynebacterial Stimulon data.

5) Detection of ‘putative contradictions’ in microarrays based on known gene regulatory networks and predicted operons (CoMa feature).

Web service integration --

Clients for GenDB and EMMA -

CoryneRegNet profits on several aspects from the direct connection to GenDB and EMMA:

1) To a gene of interest, more accurate and up to date annotation data from GenDB is displayed in the detailed view of a gene (EC numbers for enzymes, Gene Ontology numbers, etc.).

2) Using the GenDB Web Service, all target genes of a transcription factor are linked to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and a list of regulated pathways are presented. This allows insights into the general nature of a ‘transcription factor’.

3) The built-in network visualization Applet GraphVis features the projection of Stimulon data (gene expression levels) extracted from EMMA to the size of the concerned nodes, which represent the genes.

Web Service Server -

The publicly available Web Service server offers several methods to query data from CoryneRegNet. All Application Programming Interface (API) information is provided as a Web Services Description Language (WSDL) file.

The WSDL file for the interface of CoryneRegNet is automatically generated on demand by a PHP/SOAP script, which also implements the Web Service functions.

The following methods are provided:

1) getOrganisms - Compares a given string to all organism names in the database and returns the unique organism identifier (ID) for all matches.

2) getTfGeneIDs - Returns all identifiers of genes that code for transcription factors, for a given organism ID.

3) getGeneID - Genes can have ambiguous IDs in different databases and most of them are additionally stored in CoryneRegNet. This method returns unique internal gene IDs, given an ambiguous one.

4) regulates - For a given gene X, all genes that are regulated by X are returned, including additional information (evidence, regulation type, PubMed ID, etc.).

5) isRegulatedBy - For a given gene X, all genes that regulate X are returned, including additional information.

6) getOperonByGeneID - Returns operon information for a given gene ID.

It is now possible to retrieve the most important data from CoryneRegNet directly from any software that is written in a programming language which offers a SOAP interface. Such a program can internally handle all queried data as if the data is stored in local data structures and memory.

Detailed documentation (with examples) on how to implement a CoryneRegNet Web Service client is available at the CoryneRegNet 4.0 web site.

Protein cluster integration with FORCE --

The manufacturer's recently developed FORCE, an algorithm that heuristically solves the weighted graph cluster editing problem (WGCEP).

The CoMa feature --

The CoMa (Contradictions in Microarrays) feature is a novel option in the CoryneRegNet front-end to facilitate consistency checks in microarrays with known regulatory networks. The user has three (3) possibilities to enter ‘gene expression’ data:

1) Copy/paste into a text field;

2) Upload a TAB-delimited flat file; or

3) Usage of Stimulon data from the CoryneRegNet database.

This method provides hints for incorrectly predicted operons, missing gene regulatory interactions and putative errors in the experimental results.

Microarray results can be uploaded or copy/pasted easily and are subsequently checked for consistency with the known gene regulations of the integrated corynebacteria, mycobacteria, and Escherichia coli.

Additional data presentation, analysis, and visualization features --

The Web Service client for GenDB allows the presentation of more up to date ‘gene annotation’ data for a displayed gene at the CoryneRegNet website. Listed are a description, comments, and an assigned function with evidence and confidence.

Furthermore, an EC number for enzymes, COG numbers (with links to COG), and GO numbers (with links to Gene Ontology) are presented. All target genes of a transcription factor are additionally mapped to KEGG pathways (with links to KEGG) (as mentioned above). Hence, a list of regulated pathways can be presented.

The Web Service client for EMMA provides data on gene expression. Further, Stimulons have been directly integrated into the CoryneRegNet database back-end. The network visualization feature GraphVis now allows the inter-species comparisons of reconstructed ‘gene regulatory networks’ and the projection of ‘gene expression’ levels onto those networks.

Two (2) Cytoscape plug-ins are also provided, which enable the download of the CoryneRegNet database content into the Cytoscape environment.

Note: Web-Based CoryneRegNet 5.0 is a ‘Reference Database and Analysis platform’ for Corynebacterial Transcription Factors and Regulatory Networks that consist of a Release 5.0p - Predicted and a Release 5.0e – Experimental.

System Requirements

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Manufacturer Web Site CoryneRegNet

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G6G Abstract Number 20564

G6G Manufacturer Number 104171