Inference for reaction networks using the Linear Noise Approximation

We consider inference for the reaction rates in discretely observed networks such as those found in models for systems biology, population ecology and epidemics. Most such networks are neither slow enough nor small enough for inference via the true state-dependent Markov jump process to be feasible. Typically, inference is conducted by approximating the dynamics through an ordinary differential equation (ODE), or a stochastic differential equation (SDE). The former ignores the stochasticity in the true model, and can lead to inaccurate inferences. The latter is more accurate but is harder to implement as the transition density of the SDE model is generally unknown. The Linear Noise Approximation (LNA) is a first order Taylor expansion of the approximating SDE about a deterministic solution and can be viewed as a compromise between the ODE and SDE models. It is a stochastic model, but discrete time transition probabilities for the LNA are available through the solution of a series of ordinary differential equations. We describe how a restarting LNA can be efficiently used to perform inference for a general class of reaction networks; evaluate the accuracy of such an approach; and show how and when this approach is either statistically or computationally more efficient than ODE or SDE methods. We apply the LNA to analyse Google Flu Trends data from the North and South Islands of New Zealand, and are able to obtain more accurate short-term forecasts of new flu cases than another recently proposed method, although at a greater computational cost

Simulation of multivariate diffusion bridge

We propose simple methods for multivariate diffusion bridge simulation, which plays a fundamental role in simulation-based likelihood and Bayesian inference for stochastic differential equations. By a novel application of classical coupling methods, the new approach generalizes a previously proposed simulation method for one-dimensional bridges to the multi-variate setting. First a method of simulating approximate, but often very accurate, diffusion bridges is proposed. These approximate bridges are used as proposal for easily implementable MCMC algorithms that produce exact diffusion bridges. The new method is much more generally applicable than previous methods. Another advantage is that the new method works well for diffusion bridges in long intervals because the computational complexity of the method is linear in the length of the interval. In a simulation study the new method performs well, and its usefulness is illustrated by an application to Bayesian estimation for the multivariate hyperbolic diffusion model.Comment: arXiv admin note: text overlap with arXiv:1403.176

Scalable Inference for Markov Processes with Intractable Likelihoods

Bayesian inference for Markov processes has become increasingly relevant in recent years. Problems of this type often have intractable likelihoods and prior knowledge about model rate parameters is often poor. Markov Chain Monte Carlo (MCMC) techniques can lead to exact inference in such models but in practice can suffer performance issues including long burn-in periods and poor mixing. On the other hand approximate Bayesian computation techniques can allow rapid exploration of a large parameter space but yield only approximate posterior distributions. Here we consider the combined use of approximate Bayesian computation (ABC) and MCMC techniques for improved computational efficiency while retaining exact inference on parallel hardware

Bayesian inference of biochemical kinetic parameters using the linear noise approximation

Background Fluorescent and luminescent gene reporters allow us to dynamically quantify changes in molecular species concentration over time on the single cell level. The mathematical modeling of their interaction through multivariate dynamical models requires the deveopment of effective statistical methods to calibrate such models against available data. Given the prevalence of stochasticity and noise in biochemical systems inference for stochastic models is of special interest. In this paper we present a simple and computationally efficient algorithm for the estimation of biochemical kinetic parameters from gene reporter data. Results We use the linear noise approximation to model biochemical reactions through a stochastic dynamic model which essentially approximates a diffusion model by an ordinary differential equation model with an appropriately defined noise process. An explicit formula for the likelihood function can be derived allowing for computationally efficient parameter estimation. The proposed algorithm is embedded in a Bayesian framework and inference is performed using Markov chain Monte Carlo. Conclusion The major advantage of the method is that in contrast to the more established diffusion approximation based methods the computationally costly methods of data augmentation are not necessary. Our approach also allows for unobserved variables and measurement error. The application of the method to both simulated and experimental data shows that the proposed methodology provides a useful alternative to diffusion approximation based methods

Simulation based sequential Monte Carlo methods for discretely observed Markov processes

Parameter estimation for discretely observed Markov processes is a challenging problem. However, simulation of Markov processes is straightforward using the Gillespie algorithm. We exploit this ease of simulation to develop an effective sequential Monte Carlo (SMC) algorithm for obtaining samples from the posterior distribution of the parameters. In particular, we introduce two key innovations, coupled simulations, which allow us to study multiple parameter values on the basis of a single simulation, and a simple, yet effective, importance sampling scheme for steering simulations towards the observed data. These innovations substantially improve the efficiency of the SMC algorithm with minimal effect on the speed of the simulation process. The SMC algorithm is successfully applied to two examples, a Lotka-Volterra model and a Repressilator model.Comment: 27 pages, 5 figure