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Network-based confidence scoring system for genome-scale metabolic reconstructions

Reliability on complex biological networks reconstructions remains a concern. Although observations are getting more and more precise, the data collection process is yet error prone and the proofs display uneven certitude. In the case of metabolic networks, the currently employed confidence scoring system rates reactions according to a discretized small set of labels denoting different levels of experimental evidence or model-based likelihood. Here, we propose a computational network-based system of reaction scoring that exploits the complex hierarchical structure and the statistical regularities of the metabolic network as a bipartite graph. We use the example of Escherichia coli metabolism to illustrate our methodology. Our model is adjusted to the observations in order to derive connection probabilities between individual metabolite-reaction pairs and, after validation, we integrate individual link information to assess the reliability of each reaction in probabilistic terms. This network-based scoring system breaks the degeneracy of currently employed scores, enables further confirmation of modeling results, uncovers very specific reactions that could be functionally or evolutionary important, and identifies prominent experimental targets for further verification. We foresee a wide range of potential applications of our approach given the natural network bipartivity of many biological interactions.