Abstract

Understanding the mechanisms underlying the observed dynamics of complex biological systems requires the statistical assessment and comparison of multiple alternative models. Although this has traditionally been done using maximum likelihood-based methods such as Akaike's Information Criterion (AIC), Bayesian methods have gained in popularity because they provide more informative output in the form of posterior probability distributions. However, comparison between multiple models in a Bayesian framework is made difficult by the computational cost of numerical integration over large parameter spaces. A new, efficient method for the computation of posterior probabilities has recently been proposed and applied to complex problems from the physical sciences. Here we demonstrate how nested sampling can be used for inference and model comparison in biological sciences. We present a reanalysis of data from experimental infection of mice with Salmonella enterica showing the distribution of bacteria in liver cells. In addition to confirming the main finding of the original analysis, which relied on AIC, our approach provides: (a) integration across the parameter space, (b) estimation of the posterior parameter distributions (with visualisations of parameter correlations), and (c) estimation of the posterior predictive distributions for goodness-of-fit assessments of the models. The goodness-of-fit results suggest that alternative mechanistic models and a relaxation of the quasi-stationary assumption should be considered.

Highlights

  • Model comparison Model-based inference is widely used in life sciences in order to assess the plausibility of hypothesised biological mechanisms based on data from observations or experiments

  • The reason why (6) is important is that the multivariate integral on the left-hand side has been equated to a univariate integral

  • Since h has a distribution defined by prior p, and L~L(h), it follows that L has a probability distribution and a cumulative distribution function, ðl FL(l)~p(Lvl)~ fL(y) dy, ð7Þ

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Summary

Introduction

Model comparison Model-based inference is widely used in life sciences in order to assess the plausibility of hypothesised biological mechanisms based on data from observations or experiments. For a given data set D, the plausibility of the candidate models Mi is assessed by calculating their respective AIC values, AICi : AICi~{2 ln p(DDbhMLE,i,Mi)z2ndf ,i: ð1Þ. In (1), bhMLE,i is the maximum likelihood estimate of the set parameters associated with model Mi, and ndf is the corresponding number of degrees of freedom. If AIC1vAIC2 M1 is more plausible than M2, with respect to D, in the sense that the Kullback-Liebler divergence of M1 from the true model is smaller [2]. An important drawback to the classic approach to model choice is that it is based on a single point estimate bhMLE,i of h, the uncertainty in h being ignored. The Bayesian approach considers a probability distribution for h, with p(h(i)DD,Mi) expressing the uncertainty in h(i) given D (for a model M(i))

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