Department of Computer Science and Systems Engineering, Faculty of Engineering, University of Miyazaki, Miyazaki, Japan.
PLoS One. 2019 Feb 12;14(2):e0211654. doi: 10.1371/journal.pone.0211654. eCollection 2019.
Mathematical models for signaling pathways are helpful for understanding molecular mechanism in the pathways and predicting dynamic behavior of the signal activity. To analyze the robustness of such models, local sensitivity analysis has been implemented. However, such analysis primarily focuses on only a certain parameter set, even though diverse parameter sets that can recapitulate experiments may exist. In this study, we performed sensitivity analysis that investigates the features in a system considering the reproducible and multiple candidate values of the model parameters to experiments. The results showed that although different reproducible model parameter values have absolute differences with respect to sensitivity strengths, specific trends of some relative sensitivity strengths exist between reactions regardless of parameter values. It is suggested that (i) network structure considerably influences the relative sensitivity strength and (ii) one might be able to predict relative sensitivity strengths specified in the parameter sets employing only one of the reproducible parameter sets.
信号通路的数学模型有助于理解通路中的分子机制,并预测信号活性的动态行为。为了分析此类模型的稳健性,已经实施了局部敏感性分析。然而,这种分析主要集中在某个参数集上,尽管可能存在能够重现实验的多种参数集。在这项研究中,我们进行了敏感性分析,考虑到模型参数的可重复和多个候选值,研究了系统中的特征。结果表明,尽管不同的可重复模型参数值在敏感性强度方面存在绝对差异,但无论参数值如何,反应之间某些相对敏感性强度的特定趋势都存在。这表明(i)网络结构对相对敏感性强度有很大影响,(ii)仅使用一个可重复参数集,就可以预测参数集中指定的相对敏感性强度。