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Identifying All Moiety Conservation Laws in Genome-Scale Metabolic Networks

机译:识别基因组规模代谢网络中的所有部分守恒律

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摘要

The stoichiometry of a metabolic network gives rise to a set of conservation laws for the aggregate level of specific pools of metabolites, which, on one hand, pose dynamical constraints that cross-link the variations of metabolite concentrations and, on the other, provide key insight into a cell's metabolic production capabilities. When the conserved quantity identifies with a chemical moiety, extracting all such conservation laws from the stoichiometry amounts to finding all non-negative integer solutions of a linear system, a programming problem known to be NP-hard. We present an efficient strategy to compute the complete set of integer conservation laws of a genome-scale stoichiometric matrix, also providing a certificate for correctness and maximality of the solution. Our method is deployed for the analysis of moiety conservation relationships in two large-scale reconstructions of the metabolism of the bacterium E. coli, in six tissue-specific human metabolic networks, and, finally, in the human reactome as a whole, revealing that bacterial metabolism could be evolutionarily designed to cover broader production spectra than human metabolism. Convergence to the full set of moiety conservation laws in each case is achieved in extremely reduced computing times. In addition, we uncover a scaling relation that links the size of the independent pool basis to the number of metabolites, for which we present an analytical explanation.
机译:代谢网络的化学计量关系产生了一组针对特定代谢物总水平的守恒定律,一方面,这些规律构成了动力学约束,这些动力学约束使代谢物浓度的变化相互联系,另一方面,洞察细胞的代谢产生能力。当保守量与化学部分相符时,从化学计量中提取所有这样的保守定律就等于找到线性系统的所有非负整数解,这是一个已知为NP-hard的编程问题。我们提出了一种有效的策略来计算基因组规模化学计量矩阵的整数守恒律的完整集合,还提供了溶液正确性和最大性的证明。我们的方法被用于分析细菌大肠埃希氏菌的两个大规模重构,六个组织特异性人类代谢网络,以及最终整个人类反应组中的部分保守关系。细菌代谢可以通过进化设计以覆盖比人类代谢更广泛的生产光谱。在每种情况下,都可以通过大大减少的计算时间来收敛到全部的部分守恒律。此外,我们发现了一个比例关系,该比例关系将独立库基础的大小与代谢物的数量联系起来,为此我们提供了一个分析解释。

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