Dataset Information

Identification of parameter correlations for parameter estimation in dynamic biological models.

ABSTRACT:

Background

One 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.

Results

In 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.

Conclusions

The 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.

SUBMITTER: Li P

PROVIDER: S-EPMC4015753 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of parameter correlations for parameter estimation in dynamic biological models.

Li Pu P Vu Quoc Dong QD

BMC systems biology 20130922

<h4>Background</h4>One 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.<h4>Results</h4>In this study we present an approach that is a ...[more]

PMID: 24053643

Similar Datasets

Project description:BackgroundDynamic modelling is a core element in the systems biology approach to understanding complex biosystems. Here, we consider the problem of parameter estimation in models of biological oscillators described by deterministic nonlinear differential equations. These problems can be extremely challenging due to several common pitfalls: (i) a lack of prior knowledge about parameters (i.e. massive search spaces), (ii) convergence to local optima (due to multimodality of the cost function), (iii) overfitting (fitting the noise instead of the signal) and (iv) a lack of identifiability. As a consequence, the use of standard estimation methods (such as gradient-based local ones) will often result in wrong solutions. Overfitting can be particularly problematic, since it produces very good calibrations, giving the impression of an excellent result. However, overfitted models exhibit poor predictive power. Here, we present a novel automated approach to overcome these pitfalls. Its workflow makes use of two sequential optimisation steps incorporating three key algorithms: (1) sampling strategies to systematically tighten the parameter bounds reducing the search space, (2) efficient global optimisation to avoid convergence to local solutions, (3) an advanced regularisation technique to fight overfitting. In addition, this workflow incorporates tests for structural and practical identifiability.ResultsWe successfully evaluate this novel approach considering four difficult case studies regarding the calibration of well-known biological oscillators (Goodwin, FitzHugh-Nagumo, Repressilator and a metabolic oscillator). In contrast, we show how local gradient-based approaches, even if used in multi-start fashion, are unable to avoid the above-mentioned pitfalls.ConclusionsOur approach results in more efficient estimations (thanks to the bounding strategy) which are able to escape convergence to local optima (thanks to the global optimisation approach). Further, the use of regularisation allows us to avoid overfitting, resulting in more generalisable calibrated models (i.e. models with greater predictive power).

Dataset Information

Identification of parameter correlations for parameter estimation in dynamic biological models.

Background

Results

Conclusions

Publications

Identification of parameter correlations for parameter estimation in dynamic biological models.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets