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BMC Systems Biology

, 7:91

Methods, software and technology

Abstract

BackgroundOne of the challenging tasks in systems biology is parameter estimation in nonlinear dynamic models. A biological model usually contains a large number of correlated parameters leading to non-identifiability problems. Although many approaches have been developed to address both structural and practical non-identifiability problems, very few studies have been made to systematically investigate parameter correlations.

ResultsIn this study we present an approach that is able to identify both pairwise parameter correlations and higher order interrelationships among parameters in nonlinear dynamic models. Correlations are interpreted as surfaces in the subspaces of correlated parameters. Based on the correlation information obtained in this way both structural and practical non-identifiability can be clarified. Moreover, it can be concluded from the correlation analysis that a minimum number of data sets with different inputs for experimental design are needed to relieve the parameter correlations, which corresponds to the maximum number of correlated parameters among the correlation groups.

ConclusionsThe information of pairwise and higher order interrelationships among parameters in biological models gives a deeper insight into the cause of non-identifiability problems. The result of our correlation analysis provides a necessary condition for experimental design in order to acquire suitable measurement data for unique parameter estimation.

KeywordsParameter estimation Identifiability Parameter correlation Data sets with different inputs Zero residual surfaces Experimental design Electronic supplementary materialThe online version of this article doi:10.1186-1752-0509-7-91 contains supplementary material, which is available to authorized users.

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Autor: Pu Li - Quoc Dong Vu

Fuente: https://link.springer.com/



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