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

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. Here we develop such a model selection framework based on approximate Bayesian computation and employing sequential Monte Carlo sampling. We show that our approach can be applied across a wide range of biological scenarios, and we illustrate its use on real data describing influenza dynamics and the JAK-STAT signalling pathway. Bayesian model selection strikes a balance between the complexity of the simulation models and their ability to describe observed data. The present approach enables us to employ the whole formal apparatus to any system that can be (efficiently) simulated, even when exact likelihoods are computationally intractable.Comment: This article is in press in Bioinformatics, 2009. Advance Access is available on Bioinformatics webpag

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

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.Comment: 26 pages, 9 figure

Accelerating delayed-acceptance Markov chain Monte Carlo algorithms

Delayed-acceptance Markov chain Monte Carlo (DA-MCMC) samples from a probability distribution via a two-stages version of the Metropolis-Hastings algorithm, by combining the target distribution with a "surrogate" (i.e. an approximate and computationally cheaper version) of said distribution. DA-MCMC accelerates MCMC sampling in complex applications, while still targeting the exact distribution. We design a computationally faster, albeit approximate, DA-MCMC algorithm. We consider parameter inference in a Bayesian setting where a surrogate likelihood function is introduced in the delayed-acceptance scheme. When the evaluation of the likelihood function is computationally intensive, our scheme produces a 2-4 times speed-up, compared to standard DA-MCMC. However, the acceleration is highly problem dependent. Inference results for the standard delayed-acceptance algorithm and our approximated version are similar, indicating that our algorithm can return reliable Bayesian inference. As a computationally intensive case study, we introduce a novel stochastic differential equation model for protein folding data.Comment: 40 pages, 21 figures, 10 table

Ecological non-linear state space model selection via adaptive particle Markov chain Monte Carlo (AdPMCMC)

We develop a novel advanced Particle Markov chain Monte Carlo algorithm that is capable of sampling from the posterior distribution of non-linear state space models for both the unobserved latent states and the unknown model parameters. We apply this novel methodology to five population growth models, including models with strong and weak Allee effects, and test if it can efficiently sample from the complex likelihood surface that is often associated with these models. Utilising real and also synthetically generated data sets we examine the extent to which observation noise and process error may frustrate efforts to choose between these models. Our novel algorithm involves an Adaptive Metropolis proposal combined with an SIR Particle MCMC algorithm (AdPMCMC). We show that the AdPMCMC algorithm samples complex, high-dimensional spaces efficiently, and is therefore superior to standard Gibbs or Metropolis Hastings algorithms that are known to converge very slowly when applied to the non-linear state space ecological models considered in this paper. Additionally, we show how the AdPMCMC algorithm can be used to recursively estimate the Bayesian Cram\'er-Rao Lower Bound of Tichavsk\'y (1998). We derive expressions for these Cram\'er-Rao Bounds and estimate them for the models considered. Our results demonstrate a number of important features of common population growth models, most notably their multi-modal posterior surfaces and dependence between the static and dynamic parameters. We conclude by sampling from the posterior distribution of each of the models, and use Bayes factors to highlight how observation noise significantly diminishes our ability to select among some of the models, particularly those that are designed to reproduce an Allee effect

Unbiased and Consistent Nested Sampling via Sequential Monte Carlo

We introduce a new class of sequential Monte Carlo methods called Nested Sampling via Sequential Monte Carlo (NS-SMC), which reframes the Nested Sampling method of Skilling (2006) in terms of sequential Monte Carlo techniques. This new framework allows convergence results to be obtained in the setting when Markov chain Monte Carlo (MCMC) is used to produce new samples. An additional benefit is that marginal likelihood estimates are unbiased. In contrast to NS, the analysis of NS-SMC does not require the (unrealistic) assumption that the simulated samples be independent. As the original NS algorithm is a special case of NS-SMC, this provides insights as to why NS seems to produce accurate estimates despite a typical violation of its assumptions. For applications of NS-SMC, we give advice on tuning MCMC kernels in an automated manner via a preliminary pilot run, and present a new method for appropriately choosing the number of MCMC repeats at each iteration. Finally, a numerical study is conducted where the performance of NS-SMC and temperature-annealed SMC is compared on several challenging and realistic problems. MATLAB code for our experiments is made available at https://github.com/LeahPrice/SMC-NS .Comment: 45 pages, some minor typographical errors fixed since last versio

Bayesian Inference on Dynamic Models with Latent Factors

In time series analysis, latent factors are often introduced to model the heterogeneous time evolution of the observed processes. The presence of unobserved components makes the maximum likelihood estimation method more difficult to apply. A Bayesian approach can sometimes be preferable since it permits to treat general state space models and makes easier the simulation based approach to parameters estimation and latent factors filtering. The paper examines economic time series models in a Bayesian perspective focusing, through some examples, on the extraction of the business cycle components. We briefly review some general univariate Bayesian dynamic models and discuss the simulation based techniques, such as Gibbs sampling, adaptive importance sampling and finally suggest the use of the particle filter, for parameter estimation and latent factor extraction.Bayesian Dynamic Models, Simulation Based Inference, Particle Filters, Latent Factors, Business Cycle