Optimizing Threshold - Schedules for Approximate Bayesian Computation Sequential Monte Carlo Samplers: Applications to Molecular Systems

The likelihood-free sequential Approximate Bayesian Computation (ABC) algorithms, are increasingly popular inference tools for complex biological models. Such algorithms proceed by constructing a succession of probability distributions over the parameter space conditional upon the simulated data lying in an $epsilon$--ball around the observed data, for decreasing values of the threshold $epsilon$. While in theory, the distributions (starting from a suitably defined prior) will converge towards the unknown posterior as $epsilon$ tends to zero, the exact sequence of thresholds can impact upon the computational efficiency and success of a particular application. In particular, we show here that the current preferred method of choosing thresholds as a pre-determined quantile of the distances between simulated and observed data from the previous population, can lead to the inferred posterior distribution being very different to the true posterior. Threshold selection thus remains an important challenge. Here we propose an automated and adaptive method that allows us to balance the need to minimise the threshold with computational efficiency. Moreover, our method which centres around predicting the threshold - acceptance rate curve using the unscented transform, enables us to avoid local minima - a problem that has plagued previous threshold schemes.

Designing Attractive Models via Automated Identification of Chaotic and Oscillatory Dynamical Regimes

Chaos and oscillations continue to capture the interest of both the scientific and public domains. Yet despite the importance of these qualitative features, most attempts at constructing mathematical models of such phenomena have taken an indirect, quantitative approach, e.g. by fitting models to a finite number of data-points. Here we develop a qualitative inference framework that allows us to both reverse engineer and design systems exhibiting these and other dynamical behaviours by directly specifying the desired characteristics of the underlying dynamical attractor. This change in perspective from quantitative to qualitative dynamics, provides fundamental and new insights into the properties of dynamical systems.

Bayesian design of synthetic biological systems

Here we introduce a new design framework for synthetic biology that exploits the advantages of Bayesian model selection. We will argue that the difference between inference and design is that in the former we try to reconstruct the system that has given rise to the data that we observe, while in the latter, we seek to construct the system that produces the data that we would like to observe, i.e. the desired behavior. Our approach allows us to exploit methods from Bayesian statistics, including efficient exploration of models spaces and high-dimensional parameter spaces, and the ability to rank models with respect to their ability to generate certain types of data. Bayesian model selection furthermore automatically strikes a balance between complexity and (predictive or explanatory) performance of mathematical models. In order to deal with the complexities of molecular systems we employ an approximate Bayesian computation scheme which only requires us to simulate from different competing models in order to arrive at rational criteria for choosing between them. We illustrate the advantages resulting from combining the design and modeling (or in-silico prototyping) stages currently seen as separate in synthetic biology by reference to deterministic and stochastic model systems exhibiting adaptive and switch-like behavior, as well as bacterial two-component signaling systems.