Iterative reconstruction of a global metabolic model of Acinetobacter baylyi ADP1 using high-throughput growth phenotype and gene essentiality data.
Iterative reconstruction of a global metabolic model of Acinetobacter baylyi ADP1 using high-throughput growth phenotype and gene essentiality data.
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DOI：
10.1186/1752-0509-2-85
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发表时间：
2008-10-07
影响因子：
--
通讯作者：
Schachter V
中科院分区：
文献类型：
--
作者：
Durot M;Le Fèvre F;de Berardinis V;Kreimeyer A;Vallenet D;Combe C;Smidtas S;Salanoubat M;Weissenbach J;Schachter V
基因组规模的代谢模型是研究代谢网络全球特性的有力工具。它们提供了一种将各种类型的生物信息整合到一个单一框架中的方法，提供了关于各个物种新陈代谢的现有知识的结构化表示。我们重建了贝利不动杆菌ADP1的基于约束的代谢模型，该细菌是一种具有广谱生物降解能力的环境和生物技术应用感兴趣的土壤细菌。在从基因组注释和文献中进行初步重建之后，我们通过将其预测与大规模实验的结果进行比较来迭代地改进该模型：(1)野生型菌株在190个不同环境中的高通量生长表型；(2)来自敲除突变体库的全基因组基因重要性；以及(3)所有突变菌株在8个最低限度的培养基上的大规模生长表型。在1412个预测中，有1262个与我们的实验观测初步一致。系统地检查了不一致之处，导致了65个案例的模型更正。最终模型的预测结果与实验结果一致，包括91%的野生型生长表型、94%的基因必要性结果和94%的突变型生长表型。为了方便新陈代谢模型的开发，我们提供了一个网络界面，允许在线预测和在新陈代谢地图上可视化结果。迭代重建过程导致了显著的模型改进，表明在几种介质上的全基因组突变表型可以显著促进从基因组注释到高质量模型的转变。
Genome-scale metabolic models are powerful tools to study global properties of metabolic networks. They provide a way to integrate various types of biological information in a single framework, providing a structured representation of available knowledge on the metabolism of the respective species. We reconstructed a constraint-based metabolic model of Acinetobacter baylyi ADP1, a soil bacterium of interest for environmental and biotechnological applications with large-spectrum biodegradation capabilities. Following initial reconstruction from genome annotation and the literature, we iteratively refined the model by comparing its predictions with the results of large-scale experiments: (1) high-throughput growth phenotypes of the wild-type strain on 190 distinct environments, (2) genome-wide gene essentialities from a knockout mutant library, and (3) large-scale growth phenotypes of all mutant strains on 8 minimal media. Out of 1412 predictions, 1262 were initially consistent with our experimental observations. Inconsistencies were systematically examined, leading in 65 cases to model corrections. The predictions of the final version of the model, which included three rounds of refinements, are consistent with the experimental results for (1) 91% of the wild-type growth phenotypes, (2) 94% of the gene essentiality results, and (3) 94% of the mutant growth phenotypes. To facilitate the exploitation of the metabolic model, we provide a web interface allowing online predictions and visualization of results on metabolic maps. The iterative reconstruction procedure led to significant model improvements, showing that genome-wide mutant phenotypes on several media can significantly facilitate the transition from genome annotation to a high-quality model.
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影响因子：
9.9
作者：
de Berardinis, Veronique;Vallenet, David;Castelli, Vanina;Besnard, Marielle;Pinet, Agnes;Cruaud, Corinne;Samair, Sumitta;Lechaplais, Christophe;Gyapay, Gabor;Richez, Celine;Durot, Maxime;Kreimeyer, Annett;Le Fevre, Francois;Schaechter, Vincent;Pezo, Valerie;Doering, Volker;Scarpelli, Claude;Medigue, Claudine;Cohen, Georges N.;Marliere, Philippe;Salanoubat, Marcel;Weissenbach, Jean
通讯作者：
Weissenbach, Jean
影响因子：
4.4
作者：
KAPLAN, N;ZOSIM, Z;ROSENBERG, E
通讯作者：
ROSENBERG, E
影响因子：
2
作者：
Covert, MW;Palsson, BO
通讯作者：
Palsson, BO
大肠杆菌K-12的构造框架，单基因敲除突变体：Keio Collection。
影响因子：
9.9
作者：
通讯作者：
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影响因子：
9.9
作者：
通讯作者：
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