RESUMEN
Inferring epidemiological parameters such as the R0 from time-scaled phylogenies is a timely challenge. Most current approaches rely on likelihood functions, which raise specific issues that range from computing these functions to finding their maxima numerically. Here, we present a new regression-based Approximate Bayesian Computation (ABC) approach, which we base on a large variety of summary statistics intended to capture the information contained in the phylogeny and its corresponding lineage-through-time plot. The regression step involves the Least Absolute Shrinkage and Selection Operator (LASSO) method, which is a robust machine learning technique. It allows us to readily deal with the large number of summary statistics, while avoiding resorting to Markov Chain Monte Carlo (MCMC) techniques. To compare our approach to existing ones, we simulated target trees under a variety of epidemiological models and settings, and inferred parameters of interest using the same priors. We found that, for large phylogenies, the accuracy of our regression-ABC is comparable to that of likelihood-based approaches involving birth-death processes implemented in BEAST2. Our approach even outperformed these when inferring the host population size with a Susceptible-Infected-Removed epidemiological model. It also clearly outperformed a recent kernel-ABC approach when assuming a Susceptible-Infected epidemiological model with two host types. Lastly, by re-analyzing data from the early stages of the recent Ebola epidemic in Sierra Leone, we showed that regression-ABC provides more realistic estimates for the duration parameters (latency and infectiousness) than the likelihood-based method. Overall, ABC based on a large variety of summary statistics and a regression method able to perform variable selection and avoid overfitting is a promising approach to analyze large phylogenies.
Asunto(s)
Teorema de Bayes , Brotes de Enfermedades/estadística & datos numéricos , Ebolavirus/genética , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/virología , Modelos Estadísticos , Algoritmos , Simulación por Computador , Ebolavirus/clasificación , Ebolavirus/aislamiento & purificación , Humanos , Incidencia , Filogenia , Análisis de Regresión , Factores de Riesgo , Sierra Leona/epidemiología , Latencia del Virus/genéticaRESUMEN
Phylodynamics is a recent field that aims at using genetic sequence data to estimate epidemiological parameters such as the viral population growth rate, the number of infections in the population or even their duration. Its main underlying assumption is that the way viruses spread leaves marks in their genome. In this review, we first introduce the originality of phylodynamics inferences compared to 'classical' phylogenetic approaches. Then, we present the novelty of using phylogenies of infections compared to species trees, while giving some directions to infer of such objects. We discuss the birth of phylodynamics and its first successes, in order to present some of the questions the approach can address. Finally, we highlight some future challenges for the field.
RESUMEN
Parasite genetic diversity can provide information on disease transmission dynamics but most mathematical and statistical frameworks ignore the exact combinations of genotypes in infections. We introduce and validate a new method that combines explicit epidemiological modelling of coinfections and regression-Approximate Bayesian Computing (ABC) to detect within-host interactions. Using a susceptible-infected-susceptible (SIS) model, we show that, if sufficiently strong, within-host parasite interactions can be detected from epidemiological data. We also show that, in this simple setting, this detection is robust even in the face of some level of host heterogeneity in behaviour. These simulations results offer promising applications to analyse large datasets of multiple infection prevalence data, such as those collected for genital infections by Human Papillomaviruses (HPVs).