An improved method for statistical analysis of metabolic flux analysis using isotopomer mapping matrices with analytical expressions
An improved method for statistical analysis of metabolic flux analysis using isotopomer mapping matrices with analytical expressions
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DOI：
10.1016/s0168-1656(03)00169-x
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发表时间：
2003-10-09
影响因子：
4.1
通讯作者：
Shimizu, K
中科院分区：
文献类型：
--
作者：
Araúzo-Bravo, MJ;Shimizu, K
推导了计算同位素异构体分布向量灵敏度的解析表达式、相对于通量的加权输出矩阵以及基于同位素异构体映射矩阵（IMM）的代谢通量分析的协方差矩阵。这些表达式使我们能够实现有效的统计分析，避免了耗时的蒙特卡罗技术估计的置信区间的通量。解析表达式对于实现更快的实验设计也很有用，这需要重复计算协方差矩阵，而在实践中使用基于传统IMM的数值技术并不容易。将该方法应用于混合营养培养的集胞藻PCC 6803的中心碳代谢分析，并基于NMR和GC-MS测定的同位素分布计算了其所有通量的置信区间。发现标记实验的最佳可行混合物为70%未标记，10% [U-C-13]和20% [1，2-C-13（2）]标记的葡萄糖，以获得最可靠的代谢通量。(C)2003 Elsevier B. V.保留所有权利。
Analytical expressions were derived for calculating the sensitivities of isotopomer distribution vectors, the weighted output matrix with respect to the fluxes, and the covariance matrix for the metabolic flux analysis based on isotopomers mapping matrices (IMM). These expressions allow us to implement efficient statistical analysis, avoiding the time-consuming Monte Carlo techniques for estimating the confidence interval of the fluxes. The analytical expressions are also useful in implementing a faster design of experiment, which requires repetitive computation of the covariance matrix that is not straightforward to make in practice with the numerical techniques based on the conventional IMM. The proposed method was applied for analyzing the central carbon metabolism of the mixotrophically cultivated Synechocystis sp. PCC6803, and the confidence intervals of all its fluxes were computed based on the isotopomer distribution measured using NMR and GC-MS. It was found that the best feasible mixture for labeling experiment is 70% unlabeled, 10% [U-C-13] and 20% [1,2-C-13(2)] labeled glucose to obtain the most reliable metabolic fluxes. (C) 2003 Elsevier B.V. All rights reserved.