Sensitivity analysis of deterministic signaling pathways models

The paper is focused on application of sensitivity methods to analysis of signaling pathway models. Two basic methods are compared: local, based on standard sensitivity functions, and global, based on Sobol indices. Firstly, a general outline of modeling of signaling pathways by means of ordinary differential equations is briefly described. Afterwards, the methods of sensitivity analysis, known from literature, are introduced and illustrated with a simple example of a dynamical system of the second order. Subsequently, the analysis of the p53/Mdm2 regulatory module, which is a key element of any pathway involving p53 protein, is presented. The results of this analysis suggest that no single method should be chosen for investigation of any signaling pathway model but several of them should be applied to answer important questions about sources of heterogeneity in cells behavior, robustness of signaling pathways and possible molecular drug targets.