Large-scale evaluation of in silico gene deletions in Saccharomyces cerevisiae.
A large-scale in silico evaluation of gene deletions in Saccharomyces cerevisiae was conducted using a genome-scale reconstructed metabolic model. The effect of 599 single gene deletions on cell viability was simulated in silico and compared to published experimental results. In 526 cases (87.8%), the in silico results were in agreement with experimental observations when growth on synthetic complete medium was simulated. Viable phenotypes were correctly predicted in 89.4% (496 out of 555) and lethal phenotypes were correctly predicted in 68.2% (30 out of 44) of the cases considered. The in silico evaluation was solely based on the topological properties of the metabolic network which is based on well-established reaction stoichiometry. No interaction or regulatory information was accounted for in the in silico model. False predictions were analyzed on a case-by-case basis for four possible inadequacies of the in silico model: (1) incomplete media composition, (2) substitutable biomass components, (3) incomplete biochemical information, and (4) missing regulation. This analysis eliminated a number of false predictions and suggested a number of experimentally testable hypotheses. A genome-scale in silico model can thus be used to systematically reconcile existing data and fill in our knowledge gaps about an organism.
D019295:Computational Biology / Q000379:methods* / Q000592:standards; D030541:Databases, Genetic; D005069:Evaluation Studies as Topic; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics; D016681:Genome, Fungal; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D012986:Software Validation