论文标题

基于人群的优化酿酒酵母中糖酵解途径中的动力学参数鉴定

Population-based Optimization for Kinetic Parameter Identification in Glycolytic Pathway in Saccharomyces cerevisiae

论文作者

Weglarz-Tomczak, Ewelina, Tomczak, Jakub M., Eiben, Agoston E., Brul, Stanley

论文摘要

系统生物学中的模型是用于回答问题并更好地理解生物学现象的生物学过程的数学描述。动态模型通过单个物种的生产率和消费率代表网络。描述模型中反应速率的普通微分方程包括一组参数。这些参数是理解和分析生物系统的重要数量。此外,动力学参数的扰动与细胞中性和细胞超支因子(包括突变和环境变化)的系统上调有关。在这里,我们旨在使用公认的生物途径模型来识别参数值并指出其潜在的扰动/偏差。我们提出了基于人群的优化框架,该框架能够基于仅输入和输出数据(即选定代谢物的时间库)在动态模型中识别动力学参数。我们的方法可以处理不可测量参数的识别以及发现参数的偏差。我们以酿酒酵母的良好研究的糖酵解途径为例,介绍了我们提出的优化框架。

Models in systems biology are mathematical descriptions of biological processes that are used to answer questions and gain a better understanding of biological phenomena. Dynamic models represent the network through rates of the production and consumption for the individual species. The ordinary differential equations that describe rates of the reactions in the model include a set of parameters. The parameters are important quantities to understand and analyze biological systems. Moreover, the perturbation of the kinetic parameters are correlated with upregulation of the system by cell-intrinsic and cell-extrinsic factors, including mutations and the environment changes. Here, we aim at using well-established models of biological pathways to identify parameter values and point their potential perturbation/deviation. We present our population-based optimization framework that is able to identify kinetic parameters in the dynamic model based on only input and output data (i.e., timecourses of selected metabolites). Our approach can deal with the identification of the non-measurable parameters as well as with discovering deviation of the parameters. We present our proposed optimization framework on the example of the well-studied glycolytic pathway in Saccharomyces cerevisiae.

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