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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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The transcription unit diagram for the E. coli bglGFB operon, showing regulation by a variety of transcription factors and attenuation by BglG. The diagram is not to scale; rather, the regulatory region has been expanded to show detail with the genes compacted. Sites shown in green activate and sites shown in magenta inhibit transcription. The location of the StpA binding site is unknown.
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Figure 3: The transcription unit diagram for the E. coli bglGFB operon, showing regulation by a variety of transcription factors and attenuation by BglG. The diagram is not to scale; rather, the regulatory region has been expanded to show detail with the genes compacted. Sites shown in green activate and sites shown in magenta inhibit transcription. The location of the StpA binding site is unknown.

Mentions: The TU diagram (see Figure 3) depicts a set of co-transcribed genes in order on the chromosome, and shows the relative positions of the transcription start site and all DNA binding sites that regulate the promoter (not necessarily to scale). It also shows relevant mRNA binding sites, riboswitches, and attenuators. Mousing over a particular binding site brings up a tooltip containing additional information, including the evidence for that binding site. If a gene is part of multiple TUs (as a result of multiple promoters), the gene display page for that gene includes a separate diagram for each TU to allow the user to see which regulatory elements influence which promoter(s). Similarly, the display page for a transcription factor or other regulator includes TU diagrams for all genes regulated by that transcription factor or regulator. Clicking on a promoter arrow in a TU diagram navigates to a TU display page, which contains further details about each regulatory interaction in that TU, including transcription factor ligands, binding site sequences, and the position and sequence of different attenuation elements (e.g., the terminator, anti-terminator, pause site).


Regulatory network operations in the Pathway Tools software.

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

The transcription unit diagram for the E. coli bglGFB operon, showing regulation by a variety of transcription factors and attenuation by BglG. The diagram is not to scale; rather, the regulatory region has been expanded to show detail with the genes compacted. Sites shown in green activate and sites shown in magenta inhibit transcription. The location of the StpA binding site is unknown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: The transcription unit diagram for the E. coli bglGFB operon, showing regulation by a variety of transcription factors and attenuation by BglG. The diagram is not to scale; rather, the regulatory region has been expanded to show detail with the genes compacted. Sites shown in green activate and sites shown in magenta inhibit transcription. The location of the StpA binding site is unknown.
Mentions: The TU diagram (see Figure 3) depicts a set of co-transcribed genes in order on the chromosome, and shows the relative positions of the transcription start site and all DNA binding sites that regulate the promoter (not necessarily to scale). It also shows relevant mRNA binding sites, riboswitches, and attenuators. Mousing over a particular binding site brings up a tooltip containing additional information, including the evidence for that binding site. If a gene is part of multiple TUs (as a result of multiple promoters), the gene display page for that gene includes a separate diagram for each TU to allow the user to see which regulatory elements influence which promoter(s). Similarly, the display page for a transcription factor or other regulator includes TU diagrams for all genes regulated by that transcription factor or regulator. Clicking on a promoter arrow in a TU diagram navigates to a TU display page, which contains further details about each regulatory interaction in that TU, including transcription factor ligands, binding site sequences, and the position and sequence of different attenuation elements (e.g., the terminator, anti-terminator, pause site).

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