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

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          Abstract

          Approximate Bayesian computation methods can be used to evaluate posterior distributions without having to calculate likelihoods. In this paper we discuss and apply an approximate Bayesian computation (ABC) method based on sequential Monte Carlo (SMC) to estimate parameters of dynamical models. We show that ABC SMC gives 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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          Population growth of human Y chromosomes: a study of Y chromosome microsatellites

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            Non-linear optimization of biochemical pathways: applications to metabolic engineering and parameter estimation.

            The simulation of biochemical kinetic systems is a powerful approach that can be used for: (i) checking the consistency of a postulated model with a set of experimental measurements, (ii) answering 'what if?' questions and (iii) exploring possible behaviours of a model. Here we describe a generic approach to combine numerical optimization methods with biochemical kinetic simulations, which is suitable for use in the rational design of improved metabolic pathways with industrial significance (metabolic engineering) and for solving the inverse problem of metabolic pathways, i.e. the estimation of parameters from measured variables. We discuss the suitability of various optimization methods, focusing especially on their ability or otherwise to find global optima. We recommend that a suite of diverse optimization methods should be available in simulation software as no single one performs best for all problems. We describe how we have implemented such a simulation-optimization strategy in the biochemical kinetics simulator Gepasi and present examples of its application. The new version of Gepasi (3.20), incorporating the methodology described here, is available on the Internet at http://gepasi.dbs.aber.ac.uk/softw/Gepasi. html. prm@aber.ac.uk
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              Bayesian ranking of biochemical system models.

              There often are many alternative models of a biochemical system. Distinguishing models and finding the most suitable ones is an important challenge in Systems Biology, as such model ranking, by experimental evidence, will help to judge the support of the working hypotheses forming each model. Bayes factors are employed as a measure of evidential preference for one model over another. Marginal likelihood is a key component of Bayes factors, however computing the marginal likelihood is a difficult problem, as it involves integration of nonlinear functions in multidimensional space. There are a number of methods available to compute the marginal likelihood approximately. A detailed investigation of such methods is required to find ones that perform appropriately for biochemical modelling. We assess four methods for estimation of the marginal likelihoods required for computing Bayes factors. The Prior Arithmetic Mean estimator, the Posterior Harmonic Mean estimator, the Annealed Importance Sampling and the Annealing-Melting Integration methods are investigated and compared on a typical case study in Systems Biology. This allows us to understand the stability of the analysis results and make reliable judgements in uncertain context. We investigate the variance of Bayes factor estimates, and highlight the stability of the Annealed Importance Sampling and the Annealing-Melting Integration methods for the purposes of comparing nonlinear models. Models used in this study are available in SBML format as the supplementary material to this article.
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                Author and article information

                Journal
                13 January 2009
                Article
                10.1098/rsif.2008.0172
                0901.1925
                2fbe3f12-9222-4c24-bb5e-92385bdb9eae

                http://arxiv.org/licenses/nonexclusive-distrib/1.0/

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                Custom metadata
                Journal of the Royal Society Interface, Volume 6, Number 31, 2009, pages 187-202
                26 pages, 9 figures
                stat.CO stat.ME

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