A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology

Abstract

Genomic data allow the large-scale manual or semi-automated assembly of metabolic network reconstructions, which provide highly curated organism-specific knowledge bases. Although several genome-scale network reconstructions describe Saccharomyces cerevisiae metabolism, they differ in scope and content, and use different terminologies to describe the same chemical entities. This makes comparisons between them difficult and underscores the desirability of a consolidated metabolic network that collects and formalizes the 'community knowledge' of yeast metabolism. We describe how we have produced a consensus metabolic network reconstruction for S. cerevisiae. In drafting it, we placed special emphasis on referencing molecules to persistent databases or using database-independent forms, such as SMILES or InChI strings, as this permits their chemical structure to be represented unambiguously and in a manner that permits automated reasoning. The reconstruction is readily available via a publicly accessible database and in the Systems Biology Markup Language (http://www.comp-sys-bio.org/yeastnet). It can be maintained as a resource that serves as a common denominator for studying the systems biology of yeast. Similar strategies should benefit communities studying genome-scale metabolic networks of other organisms.

Figure 1. Degree distribution of the metabolic network

The metabolic reaction network was first summarized in a metabolite network, where metabolites are the nodes and one edge links two metabolites that co-occur in a reaction (in any role as substrates or products) as described in . For this analysis transport steps were not considered, nor were protein-protein binding reactions. The figures plot the distribution of the degree of connectivity, P(k), expressed as the fraction of metabolites that have k links out of the total number of metabolites plotted against the number of links (k) (A) in the complete network and, (B) in a network where the following metabolites were not considered: {water, proton, carbon dioxide, dioxygen, phosphate³⁻, diphosphate⁴⁻, ammonium, ATP, ADP, AMP, NAD⁺, NADH, NADP⁺, NADPH} (to be comparable with the analysis in ).

Figure 2

An example of the SBML annotation of a metabolite species using the example of ATP, as used in the reconstruction of the consensus network, illustrating its use of the Systems Biology Ontology (http://www.ebi.ac.uk/sbo/) and its MIRIAM-compliance. A. Relevant parts of the SBML code. B. An indication of the kinds of annotations included (for clarity not all are shown).

Figure 2

An example of the SBML annotation of a metabolite species using the example of ATP, as used in the reconstruction of the consensus network, illustrating its use of the Systems Biology Ontology (http://www.ebi.ac.uk/sbo/) and its MIRIAM-compliance. A. Relevant parts of the SBML code. B. An indication of the kinds of annotations included (for clarity not all are shown).