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      Simulation-based model selection for dynamical systems in systems and population biology.

      1 ,
      Bioinformatics (Oxford, England)
      Oxford University Press (OUP)

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          Abstract

          Computer simulations have become an important tool across the biomedical sciences and beyond. For many important problems several different models or hypotheses exist and choosing which one best describes reality or observed data is not straightforward. We therefore require suitable statistical tools that allow us to choose rationally between different mechanistic models of, e.g. signal transduction or gene regulation networks. This is particularly challenging in systems biology where only a small number of molecular species can be assayed at any given time and all measurements are subject to measurement uncertainty.

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          Most cited references38

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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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            Sequential Monte Carlo without likelihoods.

            Recent new methods in Bayesian simulation have provided ways of evaluating posterior distributions in the presence of analytically or computationally intractable likelihood functions. Despite representing a substantial methodological advance, existing methods based on rejection sampling or Markov chain Monte Carlo can be highly inefficient and accordingly require far more iterations than may be practical to implement. Here we propose a sequential Monte Carlo sampler that convincingly overcomes these inefficiencies. We demonstrate its implementation through an epidemiological study of the transmission rate of tuberculosis.
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              Uses and abuses of mathematics in biology.

              In the physical sciences, mathematical theory and experimental investigation have always marched together. Mathematics has been less intrusive in the life sciences, possibly because they have until recently been largely descriptive, lacking the invariance principles and fundamental natural constants of physics. Increasingly in recent decades, however, mathematics has become pervasive in biology, taking many different forms: statistics in experimental design; pattern seeking in bioinformatics; models in evolution, ecology, and epidemiology; and much else. I offer an opinionated overview of such uses--and abuses.
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                Author and article information

                Journal
                Bioinformatics
                Bioinformatics (Oxford, England)
                Oxford University Press (OUP)
                1367-4811
                1367-4803
                Jan 01 2010
                : 26
                : 1
                Affiliations
                [1 ] Division of Molecular Biosciences, Imperial College London, Wolfson Building, SW72AZ London, UK. ttoni@imperial.ac.uk
                Article
                btp619
                10.1093/bioinformatics/btp619
                2796821
                19880371
                dac0d852-75dc-45d5-b8d4-70aba5bab83b
                History

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