Large-scale evaluation of in silico gene deletions in Saccharomyces cerevisiae.
Large-scale evaluation of in silico gene deletions in Saccharomyces cerevisiae.
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DOI：
10.1089/153623103322246584
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发表时间：
2003-06-01
期刊：
影响因子：
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通讯作者：
Nielsen, Jens
中科院分区：
文献类型：
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作者：
Forster, Jochen;Famili, Iman;Nielsen, Jens
使用基因组规模重建的代谢模型对酿酒酵母中的基因缺失进行了大规模的计算机模拟评价。在计算机上模拟了599个单基因缺失对细胞活力的影响，并与已发表的实验结果进行了比较。在526例（87.8%）中，模拟在合成完全培养基上生长时，计算机模拟结果与实验观察结果一致。在89.4%（555例中的496例）中正确预测了存活表型，在68.2%（44例中的30例）中正确预测了致死表型。计算机模拟评价仅基于代谢网络的拓扑性质，其基于完善的反应化学计量。在计算机模拟模型中未考虑相互作用或监管信息。对计算机模拟模型的四个可能不足之处逐一分析了错误预测：（1）培养基组成不完整，（2）可替代的生物质组分，（3）生化信息不完整，以及（4）缺少监管。这种分析排除了一些错误的预测，并提出了一些实验验证的假设。因此，基因组规模的计算机模型可以用于系统地协调现有数据，并填补我们对生物体的知识空白。
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.