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Regulatory network operations in the Pathway Tools software.

Paley SM, Latendresse M, Karp PD - BMC Bioinformatics (2012)

Bottom Line: We introduce a novel type of enrichment analysis that asks whether a gene-expression dataset is over-represented for known regulators.We present algorithms for ranking the degree of regulatory influence of genes, and for computing the net positive and negative regulatory influences on a gene.Pathway Tools provides a comprehensive environment for manipulating molecular regulatory interactions that integrates regulatory data with an organism's genome and metabolic network.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bioinformatics Research Group, SRI International 333 Ravenswood Ave, Menlo Park, CA 94025, USA.

ABSTRACT

Background: Biologists are elucidating complex collections of genetic regulatory data for multiple organisms. Software is needed for such regulatory network data.

Results: The Pathway Tools software supports storage and manipulation of regulatory information through a variety of strategies. The Pathway Tools regulation ontology captures transcriptional and translational regulation, substrate-level regulation of enzyme activity, post-translational modifications, and regulatory pathways. Regulatory visualizations include a novel diagram that summarizes all regulatory influences on a gene; a transcription-unit diagram, and an interactive visualization of a full transcriptional regulatory network that can be painted with gene expression data to probe correlations between gene expression and regulatory mechanisms. We introduce a novel type of enrichment analysis that asks whether a gene-expression dataset is over-represented for known regulators. We present algorithms for ranking the degree of regulatory influence of genes, and for computing the net positive and negative regulatory influences on a gene.

Conclusions: Pathway Tools provides a comprehensive environment for manipulating molecular regulatory interactions that integrates regulatory data with an organism's genome and metabolic network. Curated collections of regulatory data authored using Pathway Tools are available for Escherichia coli, Bacillus subtilis, and Shewanella oneidensis.

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A subnetwork using the layered layout. This subnetwork was obtained by selecting three regulators (i.e., genes arcA, gadE, and nagC) and their direct regulatees.
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Figure 7: A subnetwork using the layered layout. This subnetwork was obtained by selecting three regulators (i.e., genes arcA, gadE, and nagC) and their direct regulatees.

Mentions: A user can select a group of genes of interest for color-highlighting on the diagram. For example, the user could select the set of all genes in a given Gene Ontology category (e.g., all genes involved in cell division) A user could also select genes that are directly or indirectly regulated by a named gene, in which case arrows are drawn to indicate regulatory relationships among the selected genes. The set of highlighted genes can be redisplayed in its own page, using a layered or ellipse layout. This redisplay focuses on a regulatory subnetwork of selected genes to facilitate inspection of regulatory relationships among a smaller set of genes of interest. Figure 7 shows an example of a subnetwork created after the selection of three groups of genes based on regulatory relationships from three specific genes.


Regulatory network operations in the Pathway Tools software.

Paley SM, Latendresse M, Karp PD - BMC Bioinformatics (2012)

A subnetwork using the layered layout. This subnetwork was obtained by selecting three regulators (i.e., genes arcA, gadE, and nagC) and their direct regulatees.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3473263&req=5

Figure 7: A subnetwork using the layered layout. This subnetwork was obtained by selecting three regulators (i.e., genes arcA, gadE, and nagC) and their direct regulatees.
Mentions: A user can select a group of genes of interest for color-highlighting on the diagram. For example, the user could select the set of all genes in a given Gene Ontology category (e.g., all genes involved in cell division) A user could also select genes that are directly or indirectly regulated by a named gene, in which case arrows are drawn to indicate regulatory relationships among the selected genes. The set of highlighted genes can be redisplayed in its own page, using a layered or ellipse layout. This redisplay focuses on a regulatory subnetwork of selected genes to facilitate inspection of regulatory relationships among a smaller set of genes of interest. Figure 7 shows an example of a subnetwork created after the selection of three groups of genes based on regulatory relationships from three specific genes.

Bottom Line: We introduce a novel type of enrichment analysis that asks whether a gene-expression dataset is over-represented for known regulators.We present algorithms for ranking the degree of regulatory influence of genes, and for computing the net positive and negative regulatory influences on a gene.Pathway Tools provides a comprehensive environment for manipulating molecular regulatory interactions that integrates regulatory data with an organism's genome and metabolic network.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bioinformatics Research Group, SRI International 333 Ravenswood Ave, Menlo Park, CA 94025, USA.

ABSTRACT

Background: Biologists are elucidating complex collections of genetic regulatory data for multiple organisms. Software is needed for such regulatory network data.

Results: The Pathway Tools software supports storage and manipulation of regulatory information through a variety of strategies. The Pathway Tools regulation ontology captures transcriptional and translational regulation, substrate-level regulation of enzyme activity, post-translational modifications, and regulatory pathways. Regulatory visualizations include a novel diagram that summarizes all regulatory influences on a gene; a transcription-unit diagram, and an interactive visualization of a full transcriptional regulatory network that can be painted with gene expression data to probe correlations between gene expression and regulatory mechanisms. We introduce a novel type of enrichment analysis that asks whether a gene-expression dataset is over-represented for known regulators. We present algorithms for ranking the degree of regulatory influence of genes, and for computing the net positive and negative regulatory influences on a gene.

Conclusions: Pathway Tools provides a comprehensive environment for manipulating molecular regulatory interactions that integrates regulatory data with an organism's genome and metabolic network. Curated collections of regulatory data authored using Pathway Tools are available for Escherichia coli, Bacillus subtilis, and Shewanella oneidensis.

Show MeSH
Related in: MedlinePlus