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      Inferring Epidemiological Dynamics with Bayesian Coalescent Inference: The Merits of Deterministic and Stochastic Models

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          Abstract

          Estimation of epidemiological and population parameters from molecular sequence data has become central to the understanding of infectious disease dynamics. Various models have been proposed to infer details of the dynamics that describe epidemic progression. These include inference approaches derived from Kingman’s coalescent theory. Here, we use recently described coalescent theory for epidemic dynamics to develop stochastic and deterministic coalescent susceptible–infected–removed (SIR) tree priors. We implement these in a Bayesian phylogenetic inference framework to permit joint estimation of SIR epidemic parameters and the sample genealogy. We assess the performance of the two coalescent models and also juxtapose results obtained with a recently published birth–death-sampling model for epidemic inference. Comparisons are made by analyzing sets of genealogies simulated under precisely known epidemiological parameters. Additionally, we analyze influenza A (H1N1) sequence data sampled in the Canterbury region of New Zealand and HIV-1 sequence data obtained from known United Kingdom infection clusters. We show that both coalescent SIR models are effective at estimating epidemiological parameters from data with large fundamental reproductive number R 0 and large population size S 0 . Furthermore, we find that the stochastic variant generally outperforms its deterministic counterpart in terms of error, bias, and highest posterior density coverage, particularly for smaller R 0 and S 0 . However, each of these inference models is shown to have undesirable properties in certain circumstances, especially for epidemic outbreaks with R 0 close to one or with small effective susceptible populations.

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          Most cited references31

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          Dating of the human-ape splitting by a molecular clock of mitochondrial DNA.

          A new statistical method for estimating divergence dates of species from DNA sequence data by a molecular clock approach is developed. This method takes into account effectively the information contained in a set of DNA sequence data. The molecular clock of mitochondrial DNA (mtDNA) was calibrated by setting the date of divergence between primates and ungulates at the Cretaceous-Tertiary boundary (65 million years ago), when the extinction of dinosaurs occurred. A generalized least-squares method was applied in fitting a model to mtDNA sequence data, and the clock gave dates of 92.3 +/- 11.7, 13.3 +/- 1.5, 10.9 +/- 1.2, 3.7 +/- 0.6, and 2.7 +/- 0.6 million years ago (where the second of each pair of numbers is the standard deviation) for the separation of mouse, gibbon, orangutan, gorilla, and chimpanzee, respectively, from the line leading to humans. Although there is some uncertainty in the clock, this dating may pose a problem for the widely believed hypothesis that the pipedal creature Australopithecus afarensis, which lived some 3.7 million years ago at Laetoli in Tanzania and at Hadar in Ethiopia, was ancestral to man and evolved after the human-ape splitting. Another likelier possibility is that mtDNA was transferred through hybridization between a proto-human and a proto-chimpanzee after the former had developed bipedalism.
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            Innate immunity to influenza virus infection.

            Influenza viruses are a major pathogen of both humans and animals. Recent studies using gene-knockout mice have led to an in-depth understanding of the innate sensors that detect influenza virus infection in a variety of cell types. Signalling downstream of these sensors induces distinct sets of effector mechanisms that block virus replication and promote viral clearance by inducing innate and adaptive immune responses. In this Review, we discuss the various ways in which the innate immune system uses pattern recognition receptors to detect and respond to influenza virus infection. We consider whether the outcome of innate sensor stimulation promotes antiviral resistance or disease tolerance, and propose rational treatment strategies for the acute respiratory disease that is caused by influenza virus infection.
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              Estimating mutation parameters, population history and genealogy simultaneously from temporally spaced sequence data.

              Molecular sequences obtained at different sampling times from populations of rapidly evolving pathogens and from ancient subfossil and fossil sources are increasingly available with modern sequencing technology. Here, we present a Bayesian statistical inference approach to the joint estimation of mutation rate and population size that incorporates the uncertainty in the genealogy of such temporally spaced sequences by using Markov chain Monte Carlo (MCMC) integration. The Kingman coalescent model is used to describe the time structure of the ancestral tree. We recover information about the unknown true ancestral coalescent tree, population size, and the overall mutation rate from temporally spaced data, that is, from nucleotide sequences gathered at different times, from different individuals, in an evolving haploid population. We briefly discuss the methodological implications and show what can be inferred, in various practically relevant states of prior knowledge. We develop extensions for exponentially growing population size and joint estimation of substitution model parameters. We illustrate some of the important features of this approach on a genealogy of HIV-1 envelope (env) partial sequences.
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                Author and article information

                Journal
                Genetics
                Genetics
                genetics
                genetics
                genetics
                Genetics
                Genetics Society of America
                0016-6731
                1943-2631
                February 2015
                19 December 2014
                19 December 2014
                : 199
                : 2
                : 595-607
                Affiliations
                [* ]Department of Computer Science, University of Auckland, Auckland, New Zealand 1010
                []Allan Wilson Centre for Molecular Ecology and Evolution, Palmerston North, New Zealand 4442
                []Massey University, Palmerston North, New Zealand 4442
                [§ ]Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland 44085
                [** ]SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland 1015
                Author notes
                [1 ]Corresponding author: Department of Computer Science, University of Auckland, 303-379, 38 Princes St., Auckland, New Zealand 1010. E-mail: alexei@ 123456cs.auckland.ac.nz
                Author information
                http://orcid.org/0000-0003-4454-2576
                Article
                172791
                10.1534/genetics.114.172791
                4317665
                25527289
                639c3fb6-0430-4fba-898d-b3c4d15b9446
                Copyright © 2015 by the Genetics Society of America

                Available freely online through the author-supported open access option.

                History
                : 30 June 2014
                : 13 December 2014
                Page count
                Pages: 13
                Categories
                Investigations

                Genetics
                bayesian inference,phylodynamics,coalescent,epidemic,stochastic
                Genetics
                bayesian inference, phylodynamics, coalescent, epidemic, stochastic

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