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首页> 外文期刊>Computer Methods and Programs in Biomedicine: An International Journal Devoted to the Development, Implementation and Exchange of Computing Methodology and Software Systems in Biomedical Research and Medical Practice >Indistinguishability and identifiability of kinetic models for the MurC reaction in peptidoglycan biosynthesis.
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Indistinguishability and identifiability of kinetic models for the MurC reaction in peptidoglycan biosynthesis.

机译：肽聚糖生物合成中MurC反应动力学模型的不可区分性和可识别性。

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摘要

An important question in Systems Biology is the design of experiments that enable discrimination between two (or more) competing chemical pathway models or biological mechanisms. In this paper analysis is performed between two different models describing the kinetic mechanism of a three-substrate three-product reaction, namely the MurC reaction in the cytoplasmic phase of peptidoglycan biosynthesis. One model involves ordered substrate binding and ordered release of the three products; the competing model also assumes ordered substrate binding, but with fast release of the three products. The two versions are shown to be distinguishable; however, if standard quasi-steady-state assumptions are made distinguishability cannot be determined. Once model structure uniqueness is ensured the experimenter must determine if it is possible to successfully recover rate constant values given the experiment observations, a process known as structural identifiability. Structural identifiability analysis is carried out for both models to determine which of the unknown reaction parameters can be determined uniquely, or otherwise, from the ideal system outputs. This structural analysis forms an integrated step towards the modelling of the full pathway of the cytoplasmic phase of peptidoglycan biosynthesis.
机译：系统生物学中的一个重要问题是设计实验，以区分两个（或多个）竞争性化学途径模型或生物学机制。在本文中，在描述三种底物三产物反应（即肽聚糖生物合成的细胞质相中的MurC反应）的动力学机制的两种不同模型之间进行分析。一种模型涉及三种产品的有序底物结合和有序释放。竞争模型还假定有序的底物结合，但是三种产品的释放速度很快。这两个版本显示为可区分;但是，如果做出标准的准稳态假设，则无法确定可区分性。一旦确定了模型结构的唯一性，实验人员就必须根据实验观察结果确定是否有可能成功恢复速率常数值，这一过程称为结构可识别性。对两个模型都进行结构可识别性分析，以确定哪些未知反应参数可以唯一地确定，或者以其他方式根据理想系统的输出确定。这种结构分析形成了对肽聚糖生物合成的胞质期完整路径建模的整合步骤。

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