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Dynamic estimation of specific fluxes in metabolic networks using non-linear dynamic optimization

机译:使用非线性动态优化动态估算代谢网络中的特定通量

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摘要

BackgroundMetabolic network models describing the biochemical reaction network and material fluxes inside microorganisms open interesting routes for the model-based optimization of bioprocesses. Dynamic metabolic flux analysis (dMFA) has lately been studied as an extension of regular metabolic flux analysis (MFA), rendering a dynamic view of the fluxes, also in non-stationary conditions. Recent dMFA implementations suffer from some drawbacks, though. More specifically, the fluxes are not estimated as specific fluxes, which are more biologically relevant. Also, the flux profiles are not smooth, and additional constraints like, e.g., irreversibility constraints on the fluxes, cannot be taken into account. Finally, in all previous methods, a basis for the null space of the stoichiometric matrix, i.e., which set of free fluxes is used, needs to be chosen. This choice is not trivial, and has a large influence on the resulting estimates.
机译:背景描述生物化学反应网络和微生物内部物质通量的代谢网络模型为基于模型的生物过程优化开辟了有趣的途径。动态代谢通量分析(dMFA)最近已作为常规代谢通量分析(MFA)的扩展进行了研究,即使在非平稳条件下,也可以动态显示通量。但是,最近的dMFA实施存在一些缺陷。更具体地,通量不被估计为比通量,其在生物学上更相关。而且,通量分布图也不平滑,并且不能考虑诸如通量的不可逆性约束之类的附加约束。最后,在所有先前的方法中,需要选择化学计量矩阵的零空间的基础,即,使用哪组自由通量。这种选择并非无关紧要,并且对所得的估计有很大的影响。

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