Sensitivity analysis of deterministic signaling pathways models

Bulletin of the Polish Academy of Sciences. Technical Sciences

M. Kardy?skaInstitute of Automatic Control, Silesian University of Technology, 16 Akademicka St., 44-100 Gliwice, PolandOther articles by this author:De Gruyter OnlineGoogle Scholar¹  J. ?miejaInstitute of Automatic Control, Silesian University of Technology, 16 Akademicka St., 44-100 Gliwice, PolandOther articles by this author:De Gruyter OnlineGoogle Scholar¹  K. Puszy?skiCorresponding authorInstitute of Automatic Control, Silesian University of Technology, 16 Akademicka St., 44-100 Gliwice, PolandEmailOther articles by this author:De Gruyter OnlineGoogle Scholar¹  P. LachorInstitute of Informatics, Silesian University of Technology, 16 Akademicka St., 44-100 Gliwice, PolandOther articles by this author:De Gruyter OnlineGoogle Scholar² 

[1] Institute of Automatic Control, Silesian University of Technology, 16 Akademicka St., 44-100 Gliwice, Poland;Institute of Informatics, Silesian University of Technology, 16 Akademicka St., 44-100 Gliwice, Poland

关键词: Keywords : signaling pathways;    sensitivity analysis.;   

DOI  :  10.2478/v10175-012-0060-3

学科分类：工程和技术（综合）

来源: Polska Akademia Nauk * Centrum Upowszechniania Nauki / Polish Academy of Sciences, Center for the Advancement of Science

【 摘 要 】

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.

【 授权许可】

Unknown