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

Locally adaptive smoothing with Markov random fields and shrinkage priors

We present a locally adaptive nonparametric curve fitting method that operates within a fully Bayesian framework. This method uses shrinkage priors to induce sparsity in order-k differences in the latent trend function, providing a combination of local adaptation and global control. Using a scale mixture of normals representation of shrinkage priors, we make explicit connections between our method and kth order Gaussian Markov random field smoothing. We call the resulting processes shrinkage prior Markov random fields (SPMRFs). We use Hamiltonian Monte Carlo to approximate the posterior distribution of model parameters because this method provides superior performance in the presence of the high dimensionality and strong parameter correlations exhibited by our models. We compare the performance of three prior formulations using simulated data and find the horseshoe prior provides the best compromise between bias and precision. We apply SPMRF models to two benchmark data examples frequently used to test nonparametric methods. We find that this method is flexible enough to accommodate a variety of data generating models and offers the adaptive properties and computational tractability to make it a useful addition to the Bayesian nonparametric toolbox.Comment: 38 pages, to appear in Bayesian Analysi

A linear noise approximation for stochastic epidemic models fit to partially observed incidence counts

Stochastic epidemic models (SEMs) fit to incidence data are critical to elucidating outbreak dynamics, shaping response strategies, and preparing for future epidemics. SEMs typically represent counts of individuals in discrete infection states using Markov jump processes (MJPs), but are computationally challenging as imperfect surveillance, lack of subject-level information, and temporal coarseness of the data obscure the true epidemic. Analytic integration over the latent epidemic process is impossible, and integration via Markov chain Monte Carlo (MCMC) is cumbersome due to the dimensionality and discreteness of the latent state space. Simulation-based computational approaches can address the intractability of the MJP likelihood, but are numerically fragile and prohibitively expensive for complex models. A linear noise approximation (LNA) that approximates the MJP transition density with a Gaussian density has been explored for analyzing prevalence data in large-population settings, but requires modification for analyzing incidence counts without assuming that the data are normally distributed. We demonstrate how to reparameterize SEMs to appropriately analyze incidence data, and fold the LNA into a data augmentation MCMC framework that outperforms deterministic methods, statistically, and simulation-based methods, computationally. Our framework is computationally robust when the model dynamics are complex and applies to a broad class of SEMs. We evaluate our method in simulations that reflect Ebola, influenza, and SARS-CoV-2 dynamics, and apply our method to national surveillance counts from the 2013--2015 West Africa Ebola outbreak

Imputation Estimators Partially Correct for Model Misspecification

Inference problems with incomplete observations often aim at estimating population properties of unobserved quantities. One simple way to accomplish this estimation is to impute the unobserved quantities of interest at the individual level and then take an empirical average of the imputed values. We show that this simple imputation estimator can provide partial protection against model misspecification. We illustrate imputation estimators' robustness to model specification on three examples: mixture model-based clustering, estimation of genotype frequencies in population genetics, and estimation of Markovian evolutionary distances. In the final example, using a representative model misspecification, we demonstrate that in non-degenerate cases, the imputation estimator dominates the plug-in estimate asymptotically. We conclude by outlining a Bayesian implementation of the imputation-based estimation.Comment: major rewrite, beta-binomial example removed, model based clustering is added to the mixture model example, Bayesian approach is now illustrated with the genetics exampl

Efficient data augmentation for fitting stochastic epidemic models to prevalence data

Stochastic epidemic models describe the dynamics of an epidemic as a disease spreads through a population. Typically, only a fraction of cases are observed at a set of discrete times. The absence of complete information about the time evolution of an epidemic gives rise to a complicated latent variable problem in which the state space size of the epidemic grows large as the population size increases. This makes analytically integrating over the missing data infeasible for populations of even moderate size. We present a data augmentation Markov chain Monte Carlo (MCMC) framework for Bayesian estimation of stochastic epidemic model parameters, in which measurements are augmented with subject-level disease histories. In our MCMC algorithm, we propose each new subject-level path, conditional on the data, using a time-inhomogeneous continuous-time Markov process with rates determined by the infection histories of other individuals. The method is general, and may be applied, with minimal modifications, to a broad class of stochastic epidemic models. We present our algorithm in the context of multiple stochastic epidemic models in which the data are binomially sampled prevalence counts, and apply our method to data from an outbreak of influenza in a British boarding school

Fitting stochastic epidemic models to gene genealogies using linear noise approximation

Phylodynamics is a set of population genetics tools that aim at reconstructing demographic history of a population based on molecular sequences of individuals sampled from the population of interest. One important task in phylodynamics is to estimate changes in (effective) population size. When applied to infectious disease sequences such estimation of population size trajectories can provide information about changes in the number of infections. To model changes in the number of infected individuals, current phylodynamic methods use non-parametric approaches, parametric approaches, and stochastic modeling in conjunction with likelihood-free Bayesian methods. The first class of methods yields results that are hard-to-interpret epidemiologically. The second class of methods provides estimates of important epidemiological parameters, such as infection and removal/recovery rates, but ignores variation in the dynamics of infectious disease spread. The third class of methods is the most advantageous statistically, but relies on computationally intensive particle filtering techniques that limits its applications. We propose a Bayesian model that combines phylodynamic inference and stochastic epidemic models, and achieves computational tractability by using a linear noise approximation (LNA) --- a technique that allows us to approximate probability densities of stochastic epidemic model trajectories. LNA opens the door for using modern Markov chain Monte Carlo tools to approximate the joint posterior distribution of the disease transmission parameters and of high dimensional vectors describing unobserved changes in the stochastic epidemic model compartment sizes (e.g., numbers of infectious and susceptible individuals). We apply our estimation technique to Ebola genealogies estimated using viral genetic data from the 2014 epidemic in Sierra Leone and Liberia.Comment: 43 pages, 6 figures in the main tex

rbrothers: R Package for Bayesian Multiple Change-Point Recombination Detection.

Phylogenetic recombination detection is a fundamental task in bioinformatics and evolutionary biology. Most of the computational tools developed to attack this important problem are not integrated into the growing suite of R packages for statistical analysis of molecular sequences. Here, we present an R package, rbrothers, that makes a Bayesian multiple change-point model, one of the most sophisticated model-based phylogenetic recombination tools, available to R users. Moreover, we equip the Bayesian change-point model with a set of pre- and post- processing routines that will broaden the application domain of this recombination detection framework. Specifically, we implement an algorithm that forms the set of input trees required by multiple change-point models. We also provide functionality for checking Markov chain Monte Carlo convergence and creating estimation result summaries and graphics. Using rbrothers, we perform a comparative analysis of two Salmonella enterica genes, fimA and fimH, that encode major and adhesive subunits of the type 1 fimbriae, respectively. We believe that rbrothers, available at R-Forge: http://evolmod.r-forge.r-project.org/, will allow researchers to incorporate recombination detection into phylogenetic workflows already implemented in R