Birth/birth-death processes and their computable transition probabilities with biological applications

Birth-death processes track the size of a univariate population, but many biological systems involve interaction between populations, necessitating models for two or more populations simultaneously. A lack of efficient methods for evaluating finite-time transition probabilities of bivariate processes, however, has restricted statistical inference in these models. Researchers rely on computationally expensive methods such as matrix exponentiation or Monte Carlo approximation, restricting likelihood-based inference to small systems, or indirect methods such as approximate Bayesian computation. In this paper, we introduce the birth(death)/birth-death process, a tractable bivariate extension of the birth-death process. We develop an efficient and robust algorithm to calculate the transition probabilities of birth(death)/birth-death processes using a continued fraction representation of their Laplace transforms. Next, we identify several exemplary models arising in molecular epidemiology, macro-parasite evolution, and infectious disease modeling that fall within this class, and demonstrate advantages of our proposed method over existing approaches to inference in these models. Notably, the ubiquitous stochastic susceptible-infectious-removed (SIR) model falls within this class, and we emphasize that computable transition probabilities newly enable direct inference of parameters in the SIR model. We also propose a very fast method for approximating the transition probabilities under the SIR model via a novel branching process simplification, and compare it to the continued fraction representation method with application to the 17th century plague in Eyam. Although the two methods produce similar maximum a posteriori estimates, the branching process approximation fails to capture the correlation structure in the joint posterior distribution

Quasi-stationary distributions

This paper contains a survey of results related to quasi-stationary distributions, which arise in the setting of stochastic dynamical systems that eventually evanesce, and which may be useful in describing the long-term behaviour of such systems before evanescence. We are concerned mainly with continuous-time Markov chains over a finite or countably infinite state space, since these processes most often arise in applications, but will make reference to results for other processes where appropriate. Next to giving an historical account of the subject, we review the most important results on the existence and identification of quasi-stationary distributions for general Markov chains, and give special attention to birth-death processes and related models. Results on the question of whether a quasi-stationary distribution, given its existence, is indeed a good descriptor of the long-term behaviour of a system before evanescence, are reviewed as well. The paper is concluded with a summary of recent developments in numerical and approximation methods

Extinction times in the subcritical stochastic SIS logistic epidemic

Many real epidemics of an infectious disease are not straightforwardly super- or sub-critical, and the understanding of epidemic models that exhibit such complexity has been identified as a priority for theoretical work. We provide insights into the near-critical regime by considering the stochastic SIS logistic epidemic, a well-known birth-and-death chain used to model the spread of an epidemic within a population of a given size $N$. We study the behaviour of the process as the population size $N$ tends to infinity. Our results cover the entire subcritical regime, including the "barely subcritical" regime, where the recovery rate exceeds the infection rate by an amount that tends to 0 as $N \to \infty$ but more slowly than $N^{-1/2}$. We derive precise asymptotics for the distribution of the extinction time and the total number of cases throughout the subcritical regime, give a detailed description of the course of the epidemic, and compare to numerical results for a range of parameter values. We hypothesise that features of the course of the epidemic will be seen in a wide class of other epidemic models, and we use real data to provide some tentative and preliminary support for this theory.Comment: Revised; 34 pages; 6 figure

Bayesian Non-Parametric Inference for Infectious Disease Data

We propose a framework for Bayesian non-parametric estimation of the rate at which new infections occur assuming that the epidemic is partially observed. The developed methodology relies on modelling the rate at which new infections occur as a function which only depends on time. Two different types of prior distributions are proposed namely using step-functions and B-splines. The methodology is illustrated using both simulated and real datasets and we show that certain aspects of the epidemic such as seasonality and super-spreading events are picked up without having to explicitly incorporate them into a parametric model

Timing of Pathogen Adaptation to a Multicomponent Treatment

The sustainable use of multicomponent treatments such as combination therapies, combination vaccines/chemicals, and plants carrying multigenic resistance requires an understanding of how their population-wide deployment affects the speed of the pathogen adaptation. Here, we develop a stochastic model describing the emergence of a mutant pathogen and its dynamics in a heterogeneous host population split into various types by the management strategy. Based on a multi-type Markov birth and death process, the model can be used to provide a basic understanding of how the life-cycle parameters of the pathogen population, and the controllable parameters of a management strategy affect the speed at which a pathogen adapts to a multicomponent treatment. Our results reveal the importance of coupling stochastic mutation and migration processes, and illustrate how their stochasticity can alter our view of the principles of managing pathogen adaptive dynamics at the population level. In particular, we identify the growth and migration rates that allow pathogens to adapt to a multicomponent treatment even if it is deployed on only small proportions of the host. In contrast to the accepted view, our model suggests that treatment durability should not systematically be identified with mutation cost. We show also that associating a multicomponent treatment with defeated monocomponent treatments can be more durable than associating it with intermediate treatments including only some of the components. We conclude that the explicit modelling of stochastic processes underlying evolutionary dynamics could help to elucidate the principles of the sustainable use of multicomponent treatments in population-wide management strategies intended to impede the evolution of harmful populations.Comment: 3 figure

Likelihood-Free Parallel Tempering

Approximate Bayesian Computational (ABC) methods (or likelihood-free methods) have appeared in the past fifteen years as useful methods to perform Bayesian analyses when the likelihood is analytically or computationally intractable. Several ABC methods have been proposed: Monte Carlo Markov Chains (MCMC) methods have been developped by Marjoramet al. (2003) and by Bortotet al. (2007) for instance, and sequential methods have been proposed among others by Sissonet al. (2007), Beaumont et al. (2009) and Del Moral et al. (2009). Until now, while ABC-MCMC methods remain the reference, sequential ABC methods have appeared to outperforms them (see for example McKinley et al. (2009) or Sisson et al. (2007)). In this paper a new algorithm combining population-based MCMC methods with ABC requirements is proposed, using an analogy with the Parallel Tempering algorithm (Geyer, 1991). Performances are compared with existing ABC algorithms on simulations and on a real example