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Framework for network modularization and Bayesian network analysis to investigate the perturbed metabolic network

机译:网络模块化和贝叶斯网络分析的框架,以研究扰动的代谢网络

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BackgroundGenome-scale metabolic network models have contributed to elucidating biological phenomena, and predicting gene targets to engineer for biotechnological applications. With their increasing importance, their precise network characterization has also been crucial for better understanding of the cellular physiology.ResultsWe herein introduce a framework for network modularization and Bayesian network analysis (FMB) to investigate organism’s metabolism under perturbation. FMB reveals direction of influences among metabolic modules, in which reactions with similar or positively correlated flux variation patterns are clustered, in response to specific perturbation using metabolic flux data. With metabolic flux data calculated by constraints-based flux analysis under both control and perturbation conditions, FMB, in essence, reveals the effects of specific perturbations on the biological system through network modularization and Bayesian network analysis at metabolic modular level. As a demonstration, this framework was applied to the genetically perturbed Escherichia coli metabolism, which is a lpdA gene knockout mutant, using its genome-scale metabolic network model.ConclusionsAfter all, it provides alternative scenarios of metabolic flux distributions in response to the perturbation, which are complementary to the data obtained from conventionally available genome-wide high-throughput techniques or metabolic flux analysis.
机译:背景技术基因组规模的代谢网络模型有助于阐明生物学现象,并预测基因靶点以进行生物技术应用工程化。随着它们的重要性越来越高,它们的精确网络表征对于更好地了解细胞生理学也至关重要。结果我们在此介绍了网络模块化和贝叶斯网络分析(FMB)框架,以研究生物在扰动下的代谢。 FMB揭示了代谢模块之间的影响方向,在这些模块中,使用代谢通量数据对特定扰动做出响应,从而将具有相似或正相关通量变化模式的反应聚集在一起。在控制和扰动条件下,通过基于约束的通量分析计算出的代谢通量数据,从本质上讲,FMB通过网络模块化和代谢模块水平的贝叶斯网络分析揭示了特定扰动对生物系统的影响。作为一个演示,该框架使用其基因组规模的代谢网络模型应用于遗传扰动的大肠埃希氏菌的代谢,这是一个lpdA基因敲除突变体。结论毕竟,它为响应扰动提供了代谢通量分布的替代方案,这些数据是对从常规可用的全基因组高通量技术或代谢通量分析获得的数据的补充。

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