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A comprehensive gene regulatory network for the diauxic shift in Saccharomyces cerevisiae.

Geistlinger L, Csaba G, Dirmeier S, Küffner R, Zimmer R - Nucleic Acids Res. (2013)

Bottom Line: Existing machine-readable resources for large-scale gene regulatory networks usually do not provide context information characterizing the activating conditions for a regulation and how targeted genes are affected.The resulting network consists of >300 multi-input regulatory interactions providing (i) activating conditions for the regulators; (ii) semi-quantitative effects on their targets; and (iii) classification of the experimental evidence.Additionally, we developed a browsable system organizing the network into pathway maps, which allows to inspect and trace the evidence for each annotated regulation in the model.

View Article: PubMed Central - PubMed

Affiliation: Practical Informatics and Bioinformatics, Institute for Informatics, Ludwig-Maximilians-Universität München, Amalienstrasse 17, 80333 Munich, Germany.

ABSTRACT
Existing machine-readable resources for large-scale gene regulatory networks usually do not provide context information characterizing the activating conditions for a regulation and how targeted genes are affected. Although this information is essentially required for data interpretation, available networks are often restricted to not condition-dependent, non-quantitative, plain binary interactions as derived from high-throughput screens. In this article, we present a comprehensive Petri net based regulatory network that controls the diauxic shift in Saccharomyces cerevisiae. For 100 specific enzymatic genes, we collected regulations from public databases as well as identified and manually curated >400 relevant scientific articles. The resulting network consists of >300 multi-input regulatory interactions providing (i) activating conditions for the regulators; (ii) semi-quantitative effects on their targets; and (iii) classification of the experimental evidence. The diauxic shift network compiles widespread distributed regulatory information and is available in an easy-to-use machine-readable form. Additionally, we developed a browsable system organizing the network into pathway maps, which allows to inspect and trace the evidence for each annotated regulation in the model.

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Pathway map of fatty acid metabolism. The map is compartmentalized (cytoplasm, peroxisome, mitochondrium and nucleus) and composed from three layers: the regulation layer on the right, which contains the TFs (light green rectangles) and the signals (green and purple ellipses for metabolites and conditions, respectively) that govern the transcription of genes (yellow rectangles) to their corresponding transcripts (green rhomboids) in the middle. The metabolic layer on the left depicts the translated enzymes (light green rectangles) that catalyze the interconversion of substrates and products (green ellipses), some of which are needed or produced from other subprocesses (blue hexagons) of the diauxic shift.
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gkt631-F5: Pathway map of fatty acid metabolism. The map is compartmentalized (cytoplasm, peroxisome, mitochondrium and nucleus) and composed from three layers: the regulation layer on the right, which contains the TFs (light green rectangles) and the signals (green and purple ellipses for metabolites and conditions, respectively) that govern the transcription of genes (yellow rectangles) to their corresponding transcripts (green rhomboids) in the middle. The metabolic layer on the left depicts the translated enzymes (light green rectangles) that catalyze the interconversion of substrates and products (green ellipses), some of which are needed or produced from other subprocesses (blue hexagons) of the diauxic shift.

Mentions: The diauxic shift and its subprocesses. On depletion of glucose, yeast switches from fermentation to respiratory growth on non-fermentable carbon sources such as glycerol, lactate, ethanol and fatty acids. Resulting pyruvate and acetyl-CoA is used to restore glucose and produce energy via gluconeogenesis and the TCA cycle, respectively. As described in the main text, we created pathway maps for each involved subprocess using CellDesigner (38). The maps are organized as exemplarily depicted in Figure 5, and each regulation is clickable and connected to the corresponding annotations designed in our annotation system (Figure 3), enabling a seamless tracing of the evidence from the schematic representation of a regulation in one of the maps down to the exact place in the curated literature.


A comprehensive gene regulatory network for the diauxic shift in Saccharomyces cerevisiae.

Geistlinger L, Csaba G, Dirmeier S, Küffner R, Zimmer R - Nucleic Acids Res. (2013)

Pathway map of fatty acid metabolism. The map is compartmentalized (cytoplasm, peroxisome, mitochondrium and nucleus) and composed from three layers: the regulation layer on the right, which contains the TFs (light green rectangles) and the signals (green and purple ellipses for metabolites and conditions, respectively) that govern the transcription of genes (yellow rectangles) to their corresponding transcripts (green rhomboids) in the middle. The metabolic layer on the left depicts the translated enzymes (light green rectangles) that catalyze the interconversion of substrates and products (green ellipses), some of which are needed or produced from other subprocesses (blue hexagons) of the diauxic shift.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3794591&req=5

gkt631-F5: Pathway map of fatty acid metabolism. The map is compartmentalized (cytoplasm, peroxisome, mitochondrium and nucleus) and composed from three layers: the regulation layer on the right, which contains the TFs (light green rectangles) and the signals (green and purple ellipses for metabolites and conditions, respectively) that govern the transcription of genes (yellow rectangles) to their corresponding transcripts (green rhomboids) in the middle. The metabolic layer on the left depicts the translated enzymes (light green rectangles) that catalyze the interconversion of substrates and products (green ellipses), some of which are needed or produced from other subprocesses (blue hexagons) of the diauxic shift.
Mentions: The diauxic shift and its subprocesses. On depletion of glucose, yeast switches from fermentation to respiratory growth on non-fermentable carbon sources such as glycerol, lactate, ethanol and fatty acids. Resulting pyruvate and acetyl-CoA is used to restore glucose and produce energy via gluconeogenesis and the TCA cycle, respectively. As described in the main text, we created pathway maps for each involved subprocess using CellDesigner (38). The maps are organized as exemplarily depicted in Figure 5, and each regulation is clickable and connected to the corresponding annotations designed in our annotation system (Figure 3), enabling a seamless tracing of the evidence from the schematic representation of a regulation in one of the maps down to the exact place in the curated literature.

Bottom Line: Existing machine-readable resources for large-scale gene regulatory networks usually do not provide context information characterizing the activating conditions for a regulation and how targeted genes are affected.The resulting network consists of >300 multi-input regulatory interactions providing (i) activating conditions for the regulators; (ii) semi-quantitative effects on their targets; and (iii) classification of the experimental evidence.Additionally, we developed a browsable system organizing the network into pathway maps, which allows to inspect and trace the evidence for each annotated regulation in the model.

View Article: PubMed Central - PubMed

Affiliation: Practical Informatics and Bioinformatics, Institute for Informatics, Ludwig-Maximilians-Universität München, Amalienstrasse 17, 80333 Munich, Germany.

ABSTRACT
Existing machine-readable resources for large-scale gene regulatory networks usually do not provide context information characterizing the activating conditions for a regulation and how targeted genes are affected. Although this information is essentially required for data interpretation, available networks are often restricted to not condition-dependent, non-quantitative, plain binary interactions as derived from high-throughput screens. In this article, we present a comprehensive Petri net based regulatory network that controls the diauxic shift in Saccharomyces cerevisiae. For 100 specific enzymatic genes, we collected regulations from public databases as well as identified and manually curated >400 relevant scientific articles. The resulting network consists of >300 multi-input regulatory interactions providing (i) activating conditions for the regulators; (ii) semi-quantitative effects on their targets; and (iii) classification of the experimental evidence. The diauxic shift network compiles widespread distributed regulatory information and is available in an easy-to-use machine-readable form. Additionally, we developed a browsable system organizing the network into pathway maps, which allows to inspect and trace the evidence for each annotated regulation in the model.

Show MeSH