RESUMEN
Bacterial populations that colonize a host can play important roles in host health, including serving as a reservoir that transmits to other hosts and from which invasive strains emerge, thus emphasizing the importance of understanding rates of acquisition and clearance of colonizing populations. Studies of colonization dynamics have been based on assessment of whether serial samples represent a single population or distinct colonization events. With the use of whole genome sequencing to determine genetic distance between isolates, a common solution to estimate acquisition and clearance rates has been to assume a fixed genetic distance threshold below which isolates are considered to represent the same strain. However, this approach is often inadequate to account for the diversity of the underlying within-host evolving population, the time intervals between consecutive measurements, and the uncertainty in the estimated acquisition and clearance rates. Here, we present a fully Bayesian model that provides probabilities of whether two strains should be considered the same, allowing us to determine bacterial clearance and acquisition from genomes sampled over time. Our method explicitly models the within-host variation using population genetic simulation, and the inference is done using a combination of Approximate Bayesian Computation (ABC) and Markov Chain Monte Carlo (MCMC). We validate the method with multiple carefully conducted simulations and demonstrate its use in practice by analyzing a collection of methicillin resistant Staphylococcus aureus (MRSA) isolates from a large recently completed longitudinal clinical study. An R-code implementation of the method is freely available at: https://github.com/mjarvenpaa/bacterial-colonization-model.
Asunto(s)
Biología Computacional/métodos , Interacciones Huésped-Patógeno/fisiología , Staphylococcus aureus Resistente a Meticilina , Modelos Biológicos , Infecciones Estafilocócicas/microbiología , Algoritmos , Teorema de Bayes , Portador Sano/microbiología , Simulación por Computador , Humanos , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Staphylococcus aureus Resistente a Meticilina/fisiología , Cavidad Nasal/microbiologíaRESUMEN
Approximate Bayesian computation (ABC) is commonly used for parameter estimation and model comparison for intractable simulator-based statistical models whose likelihood function cannot be evaluated. In this paper we instead investigate the feasibility of ABC as a generic approximate method for predictive inference, in particular, for computing the posterior predictive distribution of future observations or missing data of interest. We consider three complementary ABC approaches for this goal, each based on different assumptions regarding which predictive density of the intractable model can be sampled from. The case where only simulation from the joint density of the observed and future data given the model parameters can be used for inference is given particular attention and it is shown that the ideal summary statistic in this setting is minimal predictive sufficient instead of merely minimal sufficient (in the ordinary sense). An ABC prediction approach that takes advantage of a certain latent variable representation is also investigated. We additionally show how common ABC sampling algorithms can be used in the predictive settings considered. Our main results are first illustrated by using simple time-series models that facilitate analytical treatment, and later by using two common intractable dynamic models. Supplementary Information: The online version contains supplementary material available at 10.1007/s11222-022-10163-6.
RESUMEN
Detailed and realistic tree form generators have numerous applications in ecology and forestry. For example, the varying morphology of trees contributes differently to formation of landscapes, natural habitats of species, and eco-physiological characteristics of the biosphere. Here, we present an algorithm for generating morphological tree "clones" based on the detailed reconstruction of the laser scanning data, statistical measure of similarity, and a plant growth model with simple stochastic rules. The algorithm is designed to produce tree forms, i.e., morphological clones, similar (and not identical) in respect to tree-level structure, but varying in fine-scale structural detail. Although we opted for certain choices in our algorithm, individual parts may vary depending on the application, making it a general adaptable pipeline. Namely, we showed that a specific multipurpose procedural stochastic growth model can be algorithmically adjusted to produce the morphological clones replicated from the target experimentally measured tree. For this, we developed a statistical measure of similarity (structural distance) between any given pair of trees, which allows for the comprehensive comparing of the tree morphologies by means of empirical distributions describing the geometrical and topological features of a tree. Finally, we developed a programmable interface to manipulate data required by the algorithm. Our algorithm can be used in a variety of applications for exploration of the morphological potential of the growth models (both theoretical and experimental), arising in all sectors of plant science research.