Experimental design in systems biology, based on parameter sensitivity analysis using a Monte Carlo method:: A case study for the TNFα-mediated NF-κB signal transduction pathway
Experimental design in systems biology, based on parameter sensitivity analysis using a Monte Carlo method:: A case study for the TNFα-mediated NF-κB signal transduction pathway
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DOI：
10.1177/0037549703040943
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发表时间：
2003-12-01
影响因子：
1.6
通讯作者：
Wolkenhauer, O
中科院分区：
文献类型：
--
作者：
Cho, KH;Shin, SY;Wolkenhauer, O
信号转导通路的数学建模和动态模拟是系统生物学的一个重要课题，在后基因组时代越来越受到人们的关注。从实验数据估计模型参数仍然是该领域取得重大突破的瓶颈。本研究的目的是介绍一种新的策略，实验设计的基础上参数的敏感性分析。该方法确定了信号转导途径模型中的关键参数/变量，从而可以为实验生物学家提供关于考虑测量哪些蛋白质的指导。本文重点介绍了将这种方法应用于TNF α介导的NF-κ B通路，该通路在免疫和炎症以及控制细胞增殖，分化和凋亡中起着重要作用。提出了这一途径的数学模型，模型参数的灵敏度分析说明了该模型采用Monte Carlo方法在很宽的参数值范围内。
Mathematical modeling and dynamic simulation of signal transduction pathways is a central theme in systems biology and is increasingly attracting attention in the postgenomic era. The estimation of model parameters from experimental data remains a bottleneck for a major breakthrough in this area. This study's aim is to introduce a new strategy for experimental design based on parameter sensitivity analysis. The approach identifies key parameters/variables in a signal transduction pathway model and can thereby provide experimental biologists with guidance on which proteins to consider for measurement. The article focuses on applying this approach to the TNFalpha-mediated NF-kappaB pathway, which plays an important role in immunity and inflammation and in the control of cell proliferation, differentiation, and apoptosis. A mathematical model of this pathway is proposed, and the sensitivity analysis of model parameters is illustrated for this model by employing the Monte Carlo method over a broad range of parameter values.