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      Generalized method of moments for estimating parameters of stochastic reaction networks

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          Abstract

          Background

          Discrete-state stochastic models have become a well-established approach to describe biochemical reaction networks that are influenced by the inherent randomness of cellular events. In the last years several methods for accurately approximating the statistical moments of such models have become very popular since they allow an efficient analysis of complex networks.

          Results

          We propose a generalized method of moments approach for inferring the parameters of reaction networks based on a sophisticated matching of the statistical moments of the corresponding stochastic model and the sample moments of population snapshot data. The proposed parameter estimation method exploits recently developed moment-based approximations and provides estimators with desirable statistical properties when a large number of samples is available. We demonstrate the usefulness and efficiency of the inference method on two case studies.

          Conclusions

          The generalized method of moments provides accurate and fast estimations of unknown parameters of reaction networks. The accuracy increases when also moments of order higher than two are considered. In addition, the variance of the estimator decreases, when more samples are given or when higher order moments are included.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12918-016-0342-8) contains supplementary material, which is available to authorized users.

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          Most cited references52

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          Approximate Bayesian computation scheme for parameter inference and model selection in dynamical systems.

          Approximate Bayesian computation (ABC) methods can be used to evaluate posterior distributions without having to calculate likelihoods. In this paper, we discuss and apply an ABC method based on sequential Monte Carlo (SMC) to estimate parameters of dynamical models. We show that ABC SMC provides information about the inferability of parameters and model sensitivity to changes in parameters, and tends to perform better than other ABC approaches. The algorithm is applied to several well-known biological systems, for which parameters and their credible intervals are inferred. Moreover, we develop ABC SMC as a tool for model selection; given a range of different mathematical descriptions, ABC SMC is able to choose the best model using the standard Bayesian model selection apparatus.
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            Stochastic Approach to Chemical Kinetics

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              Bayesian parameter inference for stochastic biochemical network models using particle Markov chain Monte Carlo.

              Computational systems biology is concerned with the development of detailed mechanistic models of biological processes. Such models are often stochastic and analytically intractable, containing uncertain parameters that must be estimated from time course data. In this article, we consider the task of inferring the parameters of a stochastic kinetic model defined as a Markov (jump) process. Inference for the parameters of complex nonlinear multivariate stochastic process models is a challenging problem, but we find here that algorithms based on particle Markov chain Monte Carlo turn out to be a very effective computationally intensive approach to the problem. Approximations to the inferential model based on stochastic differential equations (SDEs) are considered, as well as improvements to the inference scheme that exploit the SDE structure. We apply the methodology to a Lotka-Volterra system and a prokaryotic auto-regulatory network.
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                Author and article information

                Contributors
                verena.wolf@uni-saarland.de
                Journal
                BMC Syst Biol
                BMC Syst Biol
                BMC Systems Biology
                BioMed Central (London )
                1752-0509
                21 October 2016
                21 October 2016
                2016
                : 10
                : 98
                Affiliations
                Department of Computer Science, Saarland University, Campus E 13, Saarbrücken, 66123 Germany
                Article
                342
                10.1186/s12918-016-0342-8
                5073941
                27769280
                a252e138-3d42-4274-a152-054e5ad55b03
                © The Author(s) 2016

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 6 May 2016
                : 11 October 2016
                Funding
                Funded by: Deutsche Forschungsgemeinschaft
                Award ID: EXC 284
                Award Recipient :
                Categories
                Methodology Article
                Custom metadata
                © The Author(s) 2016

                Quantitative & Systems biology
                biochemical reaction network,stochastic model,parameter estimation,generalized method of moments

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