Rate estimation in partially observed Markov jump processes with measurement errors

We present a simulation methodology for Bayesian estimation of rate parameters in Markov jump processes arising for example in stochastic kinetic models. To handle the problem of missing components and measurement errors in observed data, we embed the Markov jump process into the framework of a general state space model. We do not use diffusion approximations. Markov chain Monte Carlo and particle filter type algorithms are introduced which allow sampling from the posterior distribution of the rate parameters and the Markov jump process also in data-poor scenarios. The algorithms are illustrated by applying them to rate estimation in a model for prokaryotic auto-regulation and the stochastic Oregonator, respectivel

The impact of temporal sampling resolution on parameter inference for biological transport models

Imaging data has become widely available to study biological systems at various scales, for example the motile behaviour of bacteria or the transport of mRNA, and it has the potential to transform our understanding of key transport mechanisms. Often these imaging studies require us to compare biological species or mutants, and to do this we need to quantitatively characterise their behaviour. Mathematical models offer a quantitative description of a system that enables us to perform this comparison, but to relate these mechanistic mathematical models to imaging data, we need to estimate the parameters of the models. In this work, we study the impact of collecting data at different temporal resolutions on parameter inference for biological transport models by performing exact inference for simple velocity jump process models in a Bayesian framework. This issue is prominent in a host of studies because the majority of imaging technologies place constraints on the frequency with which images can be collected, and the discrete nature of observations can introduce errors into parameter estimates. In this work, we avoid such errors by formulating the velocity jump process model within a hidden states framework. This allows us to obtain estimates of the reorientation rate and noise amplitude for noisy observations of a simple velocity jump process. We demonstrate the sensitivity of these estimates to temporal variations in the sampling resolution and extent of measurement noise. We use our methodology to provide experimental guidelines for researchers aiming to characterise motile behaviour that can be described by a velocity jump process. In particular, we consider how experimental constraints resulting in a trade-off between temporal sampling resolution and observation noise may affect parameter estimates.Comment: Published in PLOS Computational Biolog

Approximate Kalman-Bucy filter for continuous-time semi-Markov jump linear systems

The aim of this paper is to propose a new numerical approximation of the Kalman-Bucy filter for semi-Markov jump linear systems. This approximation is based on the selection of typical trajectories of the driving semi-Markov chain of the process by using an optimal quantization technique. The main advantage of this approach is that it makes pre-computations possible. We derive a Lipschitz property for the solution of the Riccati equation and a general result on the convergence of perturbed solutions of semi-Markov switching Riccati equations when the perturbation comes from the driving semi-Markov chain. Based on these results, we prove the convergence of our approximation scheme in a general infinite countable state space framework and derive an error bound in terms of the quantization error and time discretization step. We employ the proposed filter in a magnetic levitation example with markovian failures and compare its performance with both the Kalman-Bucy filter and the Markovian linear minimum mean squares estimator

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

Efficient Transition Probability Computation for Continuous-Time Branching Processes via Compressed Sensing

Branching processes are a class of continuous-time Markov chains (CTMCs) with ubiquitous applications. A general difficulty in statistical inference under partially observed CTMC models arises in computing transition probabilities when the discrete state space is large or uncountable. Classical methods such as matrix exponentiation are infeasible for large or countably infinite state spaces, and sampling-based alternatives are computationally intensive, requiring a large integration step to impute over all possible hidden events. Recent work has successfully applied generating function techniques to computing transition probabilities for linear multitype branching processes. While these techniques often require significantly fewer computations than matrix exponentiation, they also become prohibitive in applications with large populations. We propose a compressed sensing framework that significantly accelerates the generating function method, decreasing computational cost up to a logarithmic factor by only assuming the probability mass of transitions is sparse. We demonstrate accurate and efficient transition probability computations in branching process models for hematopoiesis and transposable element evolution.Comment: 18 pages, 4 figures, 2 table