Dataset Information

Generalized Ordinary Differential Equation Models.

ABSTRACT: Existing estimation methods for ordinary differential equation (ODE) models are not applicable to discrete data. The generalized ODE (GODE) model is therefore proposed and investigated for the first time. We develop the likelihood-based parameter estimation and inference methods for GODE models. We propose robust computing algorithms and rigorously investigate the asymptotic properties of the proposed estimator by considering both measurement errors and numerical errors in solving ODEs. The simulation study and application of our methods to an influenza viral dynamics study suggest that the proposed methods have a superior performance in terms of accuracy over the existing ODE model estimation approach and the extended smoothing-based (ESB) method.

SUBMITTER: Miao H

PROVIDER: S-EPMC4274811 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Publications

Generalized Ordinary Differential Equation Models.

Miao Hongyu H Wu Hulin H Xue Hongqi H

Journal of the American Statistical Association 20141001 508

Existing estimation methods for ordinary differential equation (ODE) models are not applicable to discrete data. The generalized ODE (GODE) model is therefore proposed and investigated for the first time. We develop the likelihood-based parameter estimation and inference methods for GODE models. We propose robust computing algorithms and rigorously investigate the asymptotic properties of the proposed estimator by considering both measurement errors and numerical errors in solving ODEs. The simu ...[more]

PMID: 25544787

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Project description:Ordinary differential equation (ODE) models are widely used to study biochemical reactions in cellular networks since they effectively describe the temporal evolution of these networks using mass action kinetics. The parameters of these models are rarely known a priori and must instead be estimated by calibration using experimental data. Optimization-based calibration of ODE models on is often challenging, even for low-dimensional problems. Multiple hypotheses have been advanced to explain why biochemical model calibration is challenging, including non-identifiability of model parameters, but there are few comprehensive studies that test these hypotheses, likely because tools for performing such studies are also lacking. Nonetheless, reliable model calibration is essential for uncertainty analysis, model comparison, and biological interpretation. We implemented an established trust-region method as a modular Python framework (fides) to enable systematic comparison of different approaches to ODE model calibration involving a variety of Hessian approximation schemes. We evaluated fides on a recently developed corpus of biologically realistic benchmark problems for which real experimental data are available. Unexpectedly, we observed high variability in optimizer performance among different implementations of the same mathematical instructions (algorithms). Analysis of possible sources of poor optimizer performance identified limitations in the widely used Gauss-Newton, BFGS and SR1 Hessian approximation schemes. We addressed these drawbacks with a novel hybrid Hessian approximation scheme that enhances optimizer performance and outperforms existing hybrid approaches. When applied to the corpus of test models, we found that fides was on average more reliable and efficient than existing methods using a variety of criteria. We expect fides to be broadly useful for ODE constrained optimization problems in biochemical models and to be a foundation for future methods development.

Dataset Information

Generalized Ordinary Differential Equation Models.

Publications

Generalized Ordinary Differential Equation Models.

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