Version 6 of the consensus yeast metabolic network refines biochemical coverage and improves model performance.

Benjamin D Heavner,Kieran Smallbone,Nathan D Price,Larry P Walker

doi:10.1093/database/bat059

Abstract

Updates to maintain a state-of-the art reconstruction of the yeast metabolic network are essential to reflect our understanding of yeast metabolism and functional organization, to eliminate any inaccuracies identified in earlier iterations, to improve predictive accuracy and to continue to expand into novel subsystems to extend the comprehensiveness of the model. Here, we present version 6 of the consensus yeast metabolic network (Yeast 6) as an update to the community effort to computationally reconstruct the genome-scale metabolic network of Saccharomyces cerevisiae S288c. Yeast 6 comprises 1458 metabolites participating in 1888 reactions, which are annotated with 900 yeast genes encoding the catalyzing enzymes. Compared with Yeast 5, Yeast 6 demonstrates improved sensitivity, specificity and positive and negative predictive values for predicting gene essentiality in glucose-limited aerobic conditions when analyzed with flux balance analysis. Additionally, Yeast 6 improves the accuracy of predicting the likelihood that a mutation will cause auxotrophy. The network reconstruction is available as a Systems Biology Markup Language (SBML) file enriched with Minimium Information Requested in the Annotation of Biochemical Models (MIRIAM)-compliant annotations. Small- and macromolecules in the network are referenced to authoritative databases such as Uniprot or ChEBI. Molecules and reactions are also annotated with appropriate publications that contain supporting evidence. Yeast 6 is freely available at http://yeast.sf.net/ as three separate SBML files: a model using the SBML level 3 Flux Balance Constraint package, a model compatible with the MATLAB® COBRA Toolbox for backward compatibility and a reconstruction containing only reactions for which there is experimental evidence (without the non-biological reactions necessary for simulating growth).Database URL: http://yeast.sf.net/

Highlights

In 2007, a community effort to integrate previously published genome-scale reconstructions of the yeast metabolic network [1, 2] produced a ‘consensus’ representation of yeast metabolism [3], which has subsequently been updated through iterative collaborative curation by multiple research groups [4, 5]
Ninety-seven of the 1868 reactions shared between Yeast 5 and Yeast 6 have different constraints, reflecting refinements of reaction reversibility in the yeast metabolic network
Yeast 6 is the current state-of-the-art reconstruction of the S. cerevisiae metabolic network. It eliminates many inferred reactions for which there is no evidence, adds new reactions based on recent evidence and results in improved predictions of experimental data. It maintains the distinction between GENRE and GEM, and by emphasizing traceable annotation for included information, it differentiates between established biochemistry and hypotheses that may be generated by automated techniques such as gap-filling algorithms [20]

Summary

Introduction

In 2007, a community effort to integrate previously published genome-scale reconstructions of the yeast metabolic network [1, 2] produced a ‘consensus’ representation of yeast metabolism [3], which has subsequently been updated through iterative collaborative curation by multiple research groups [4, 5]. We introduce version 6 of the consensus reconstruction of the yeast metabolic network, Yeast 6. The differences between Yeast 5 and Yeast 6 are described below and are fully detailed in the supplementary data attached to this publication. This update maintains an emphasis on standards compliance, unambiguous metabolite naming and computer-readable annotations available through a structured document format.

Results

Discussion

Conclusion