Journal article
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.
Language: | English |
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Publisher: | Mary Ann Liebert, Inc. |
Year: | 2003 |
Pages: | 193-203 |
ISSN: | 15578100 and 15362310 |
Types: | Journal article |
DOI: | 10.1089/153623103322246584 |
ORCIDs: | Förster, Jochen |