Dataset Information

Network reconstruction and validation of the Snf1/AMPK pathway in baker's yeast based on a comprehensive literature review.

ABSTRACT:

Background/objectives

The SNF1/AMPK protein kinase has a central role in energy homeostasis in eukaryotic cells. It is activated by energy depletion and stimulates processes leading to the production of ATP while it downregulates ATP-consuming processes. The yeast SNF1 complex is best known for its role in glucose derepression.

Methods

We performed a network reconstruction of the Snf1 pathway based on a comprehensive literature review. The network was formalised in the rxncon language, and we used the rxncon toolbox for model validation and gap filling.

Results

We present a machine-readable network definition that summarises the mechanistic knowledge of the Snf1 pathway. Furthermore, we used the known input/output relationships in the network to identify and fill gaps in the information transfer through the pathway, to produce a functional network model. Finally, we convert the functional network model into a rule-based model as a proof-of-principle.

Conclusions

The workflow presented here enables large scale reconstruction, validation and gap filling of signal transduction networks. It is analogous to but distinct from that established for metabolic networks. We demonstrate the workflow capabilities, and the direct link between the reconstruction and dynamic modelling, with the Snf1 network. This network is a distillation of the knowledge from all previous publications on the Snf1/AMPK pathway. The network is a knowledge resource for modellers and experimentalists alike, and a template for similar efforts in higher eukaryotes. Finally, we envisage the workflow as an instrumental tool for reconstruction of large signalling networks across Eukaryota.

SUBMITTER: Lubitz T

PROVIDER: S-EPMC5516868 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Network reconstruction and validation of the Snf1/AMPK pathway in baker's yeast based on a comprehensive literature review.

Lubitz Timo T Welkenhuysen Niek N Shashkova Sviatlana S Bendrioua Loubna L Hohmann Stefan S Klipp Edda E Krantz Marcus M

NPJ systems biology and applications 20151022

<h4>Background/objectives</h4>The SNF1/AMPK protein kinase has a central role in energy homeostasis in eukaryotic cells. It is activated by energy depletion and stimulates processes leading to the production of ATP while it downregulates ATP-consuming processes. The yeast SNF1 complex is best known for its role in glucose derepression.<h4>Methods</h4>We performed a network reconstruction of the Snf1 pathway based on a comprehensive literature review. The network was formalised in the rxncon lang ...[more]

PMID: 28725459

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Project description:Molecular interaction networks establish all cell biological processes. The networks are under intensive research that is facilitated by new high-throughput measurement techniques for the detection, quantification, and characterization of molecules and their physical interactions. For the common model organism yeast Saccharomyces cerevisiae, public databases store a significant part of the accumulated information and, on the way to better understanding of the cellular processes, there is a need to integrate this information into a consistent reconstruction of the molecular interaction network. This work presents and validates RefRec, the most comprehensive molecular interaction network reconstruction currently available for yeast. The reconstruction integrates protein synthesis pathways, a metabolic network, and a protein-protein interaction network from major biological databases. The core of the reconstruction is based on a reference object approach in which genes, transcripts, and proteins are identified using their primary sequences. This enables their unambiguous identification and non-redundant integration. The obtained total number of different molecular species and their connecting interactions is approximately 67,000. In order to demonstrate the capacity of RefRec for functional predictions, it was used for simulating the gene knockout damage propagation in the molecular interaction network in approximately 590,000 experimentally validated mutant strains. Based on the simulation results, a statistical classifier was subsequently able to correctly predict the viability of most of the strains. The results also showed that the usage of different types of molecular species in the reconstruction is important for accurate phenotype prediction. In general, the findings demonstrate the benefits of global reconstructions of molecular interaction networks. With all the molecular species and their physical interactions explicitly modeled, our reconstruction is able to serve as a valuable resource in additional analyses involving objects from multiple molecular -omes. For that purpose, RefRec is freely available in the Systems Biology Markup Language format.

Dataset Information

Network reconstruction and validation of the Snf1/AMPK pathway in baker's yeast based on a comprehensive literature review.

Background/objectives

Methods

Results

Conclusions

Publications

Network reconstruction and validation of the Snf1/AMPK pathway in baker's yeast based on a comprehensive literature review.

Similar Datasets

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