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Dynamic metabolic flux analysis of underdetermined and overdetermined metabolic networks

机译：不确定和过度确定的代谢网络的动态代谢通量分析

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Abstract: In this work, two metabolic networks representing the metabolism of CHO cells in fed-batch cultures are considered. The first metabolic network is relatively detailed and underdetermined with the available extracellular measurements, while the second is a reduced version of the former and is overdetermined. A dynamic metabolic flux analysis based on convex analysis (DMFCA) is applied to the detailed network, which allows the computation of the time evolution of bounded intervals. On the other hand, a linear optimization problem is solved for the reduced-size network, with either positivity constraints or box constraints inferred from DMFCA. In all cases, smoothing splines and mass balance differential equations are used to infer the time evolution of the uptake and excretion rates from experimental data. The analysis allows to get insight into CHO metabolism as well as to investigate the influence of the size of the metabolic network.
机译：摘要：在这项工作中，考虑了两个代表补料分批培养物中CHO细胞代谢的代谢网络。第一个代谢网络相对较详细，可用细胞外测量值还不确定，而第二个代谢网络是前者的简化版本，但确定性较高。将基于凸分析的动态代谢通量分析（DMFCA）应用于详细网络，该网络可以计算有界区间的时间演化。另一方面，通过DMFCA推断的正约束或框约束，解决了尺寸减小的网络的线性优化问题。在所有情况下，都使用平滑样条和质量平衡微分方程从实验数据推断吸收和排泄速率的时间演变。该分析可以深入了解CHO代谢，并研究代谢网络大小的影响。

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