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1.
Nature ; 595(7869): 707-712, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34098568

RESUMEN

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3-5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant's success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.


Asunto(s)
COVID-19/transmisión , COVID-19/virología , SARS-CoV-2/aislamiento & purificación , Estaciones del Año , COVID-19/diagnóstico , COVID-19/epidemiología , Europa (Continente)/epidemiología , Genotipo , Humanos , Filogenia , SARS-CoV-2/genética , Factores de Tiempo , Viaje/legislación & jurisprudencia , Viaje/estadística & datos numéricos
2.
Proc Natl Acad Sci U S A ; 121(2): e2308125121, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38175864

RESUMEN

We estimate the basic reproductive number and case counts for 15 distinct Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks, distributed across 11 populations (10 countries and one cruise ship), based solely on phylodynamic analyses of genomic data. Our results indicate that, prior to significant public health interventions, the reproductive numbers for 10 (out of 15) of these outbreaks are similar, with median posterior estimates ranging between 1.4 and 2.8. These estimates provide a view which is complementary to that provided by those based on traditional line listing data. The genomic-based view is arguably less susceptible to biases resulting from differences in testing protocols, testing intensity, and import of cases into the community of interest. In the analyses reported here, the genomic data primarily provide information regarding which samples belong to a particular outbreak. We observe that once these outbreaks are identified, the sampling dates carry the majority of the information regarding the reproductive number. Finally, we provide genome-based estimates of the cumulative number of infections for each outbreak. For 7 out of 11 of the populations studied, the number of confirmed cases is much bigger than the cumulative number of infections estimated from the sequence data, a possible explanation being the presence of unsequenced outbreaks in these populations.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiología , Brotes de Enfermedades , Genómica , Navíos
3.
Proc Natl Acad Sci U S A ; 120(17): e2215610120, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-37068240

RESUMEN

In 2013 to 2017, avian influenza A(H7N9) virus has caused five severe epidemic waves of human infections in China. The role of live bird markets (LBMs) in the transmission dynamics of H7N9 remains unclear. Using a Bayesian phylodynamic approach, we shed light on past H7N9 transmission events at the human-LBM interface that were not directly observed using case surveillance data-based approaches. Our results reveal concurrent circulation of H7N9 lineages in Yangtze and Pearl River Delta regions, with evidence of local transmission during each wave. Our results indicate that H7N9 circulated in humans and LBMs for weeks to months before being first detected. Our findings support the seasonality of H7N9 transmission and suggest a high number of underreported infections, particularly in LBMs. We provide evidence for differences in virus transmissibility between low and highly pathogenic H7N9. We demonstrate a regional spatial structure for the spread of H7N9 among LBMs, highlighting the importance of further investigating the role of local live poultry trade in virus transmission. Our results provide estimates of avian influenza virus (AIV) transmission at the LBM level, providing a unique opportunity to better prepare surveillance plans at LBMs for response to future AIV epidemics.


Asunto(s)
Subtipo H7N9 del Virus de la Influenza A , Gripe Aviar , Gripe Humana , Animales , Humanos , Teorema de Bayes , Aves de Corral , China/epidemiología
4.
Bioinformatics ; 40(1)2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38195927

RESUMEN

SUMMARY: Phylodynamic models link phylogenetic trees to biologically-relevant parameters such as speciation and extinction rates (macroevolution), effective population sizes and migration rates (ecology and phylogeography), and transmission and removal/recovery rates (epidemiology) to name a few. Being able to simulate phylogenetic trees and population dynamics under these models is the basis for (i) developing and testing of phylodynamic inference algorithms, (ii) performing simulation studies which quantify the biases stemming from model-misspecification, and (iii) performing so-called model adequacy assessments by simulating samples from the posterior predictive distribution. Here I introduce ReMASTER, a package for the phylogenetic inference platform BEAST 2 that provides a simple and efficient approach to specifying and simulating the phylogenetic trees and population dynamics arising from phylodynamic models. Being a component of BEAST 2 allows ReMASTER to also form the basis of joint simulation and inference analyses. ReMASTER is a complete rewrite of an earlier package, MASTER, and boasts improved efficiency, ease of use, flexibility of model specification, and deeper integration with BEAST 2. AVAILABILITY AND IMPLEMENTATION: ReMASTER can be installed directly from the BEAST 2 package manager, and its documentation is available online at https://tgvaughan.github.io/remaster. ReMASTER is free software, and is distributed under version 3 of the GNU General Public License. The Java source code for ReMASTER is available from https://github.com/tgvaughan/remaster.


Asunto(s)
Algoritmos , Programas Informáticos , Filogenia , Simulación por Computador , Filogeografía
5.
Syst Biol ; 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39436077

RESUMEN

Time-dependent birth-death sampling models have been used in numerous studies for inferring past evolutionary dynamics in different biological contexts, e.g. speciation and extinction rates in macroevolutionary studies, or effective reproductive number in epidemiological studies. These models are branching processes where lineages can bifurcate, die, or be sampled with time-dependent birth, death, and sampling rates, generating phylogenetic trees. It has been shown that in some subclasses of such models, different sets of rates can result in the same distributions of reconstructed phylogenetic trees, and therefore the rates become unidentifiable from the trees regardless of their size. Here we show that widely used time-dependent fossilised birth-death (FBD) models are identifiable. This subclass of models makes more realistic assumptions about the fossilisation process and certain infectious disease transmission processes than the unidentifiable birth-death sampling models. Namely, FBD models assume that sampled lineages stay in the process rather than being immediately removed upon sampling. Identifiability of the time-dependent FBD model justifies using statistical methods that implement this model to infer the underlying temporal diversification or epidemiological dynamics from phylogenetic trees or directly from molecular or other comparative data. We further show that the time-dependent fossilised-birth-death model with an extra parameter, the removal after sampling probability, is unidentifiable. This implies that in scenarios where we do not know how sampling affects lineages we are unable to infer this extra parameter together with birth, death, and sampling rates solely from trees.

6.
Mol Biol Evol ; 40(6)2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37264694

RESUMEN

Despite its increasing role in the understanding of infectious disease transmission at the applied and theoretical levels, phylodynamics lacks a well-defined notion of ideal data and optimal sampling. We introduce a method to visualize and quantify the relative impact of pathogen genome sequence and sampling times-two fundamental sources of data for phylodynamics under birth-death-sampling models-to understand how each drives phylodynamic inference. Applying our method to simulated data and real-world SARS-CoV-2 and H1N1 Influenza data, we use this insight to elucidate fundamental trade-offs and guidelines for phylodynamic analyses to draw the most from sequence data. Phylodynamics promises to be a staple of future responses to infectious disease threats globally. Continuing research into the inherent requirements and trade-offs of phylodynamic data and inference will help ensure phylodynamic tools are wielded in ever more targeted and efficient ways.


Asunto(s)
COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Filogenia , SARS-CoV-2/genética
7.
Proc Natl Acad Sci U S A ; 118(9)2021 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-33571105

RESUMEN

The investigation of migratory patterns during the SARS-CoV-2 pandemic before spring 2020 border closures in Europe is a crucial first step toward an in-depth evaluation of border closure policies. Here we analyze viral genome sequences using a phylodynamic model with geographic structure to estimate the origin and spread of SARS-CoV-2 in Europe prior to border closures. Based on SARS-CoV-2 genomes, we reconstruct a partial transmission tree of the early pandemic and coinfer the geographic location of ancestral lineages as well as the number of migration events into and between European regions. We find that the predominant lineage spreading in Europe during this time has a most recent common ancestor in Italy and was probably seeded by a transmission event in either Hubei, China or Germany. We do not find evidence for preferential migration paths from Hubei into different European regions or from each European region to the others. Sustained local transmission is first evident in Italy and then shortly thereafter in the other European regions considered. Before the first border closures in Europe, we estimate that the rate of occurrence of new cases from within-country transmission was within the bounds of the estimated rate of new cases from migration. In summary, our analysis offers a view on the early state of the epidemic in Europe and on migration patterns of the virus before border closures. This information will enable further study of the necessity and timeliness of border closures.


Asunto(s)
COVID-19/epidemiología , SARS-CoV-2/aislamiento & purificación , COVID-19/virología , Europa (Continente)/epidemiología , Genoma Viral , Humanos , Filogeografía , SARS-CoV-2/genética
8.
Mol Biol Evol ; 39(1)2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34893876

RESUMEN

The structured coalescent allows inferring migration patterns between viral subpopulations from genetic sequence data. However, these analyses typically assume that no genetic recombination process impacted the sequence evolution of pathogens. For segmented viruses, such as influenza, that can undergo reassortment this assumption is broken. Reassortment reshuffles the segments of different parent lineages upon a coinfection event, which means that the shared history of viruses has to be represented by a network instead of a tree. Therefore, full genome analyses of such viruses are complex or even impossible. Although this problem has been addressed for unstructured populations, it is still impossible to account for population structure, such as induced by different host populations, whereas also accounting for reassortment. We address this by extending the structured coalescent to account for reassortment and present a framework for investigating possible ties between reassortment and migration (host jump) events. This method can accurately estimate subpopulation dependent effective populations sizes, reassortment, and migration rates from simulated data. Additionally, we apply the new model to avian influenza A/H5N1 sequences, sampled from two avian host types, Anseriformes and Galliformes. We contrast our results with a structured coalescent without reassortment inference, which assumes independently evolving segments. This reveals that taking into account segment reassortment and using sequencing data from several viral segments for joint phylodynamic inference leads to different estimates for effective population sizes, migration, and clock rates. This new model is implemented as the Structured Coalescent with Reassortment package for BEAST 2.5 and is available at https://github.com/jugne/SCORE.


Asunto(s)
Subtipo H5N1 del Virus de la Influenza A , Gripe Humana , Animales , Genoma Viral , Humanos , Subtipo H5N1 del Virus de la Influenza A/genética , Filogenia , Virus Reordenados/genética
9.
PLoS Comput Biol ; 18(8): e1010394, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35984845

RESUMEN

When two influenza viruses co-infect the same cell, they can exchange genome segments in a process known as reassortment. Reassortment is an important source of genetic diversity and is known to have been involved in the emergence of most pandemic influenza strains. However, because of the difficulty in identifying reassortment events from viral sequence data, little is known about their role in the evolution of the seasonal influenza viruses. Here we introduce TreeKnit, a method that infers ancestral reassortment graphs (ARG) from two segment trees. It is based on topological differences between trees, and proceeds in a greedy fashion by finding regions that are compatible in the two trees. Using simulated genealogies with reassortments, we show that TreeKnit performs well in a wide range of settings and that it is as accurate as a more principled bayesian method, while being orders of magnitude faster. Finally, we show that it is possible to use the inferred ARG to better resolve segment trees and to construct more informative visualizations of reassortments.


Asunto(s)
Gripe Humana , Orthomyxoviridae , Teorema de Bayes , Genoma Viral/genética , Humanos , Orthomyxoviridae/genética , Filogenia , Virus Reordenados/genética
10.
Proc Natl Acad Sci U S A ; 117(29): 17104-17111, 2020 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-32631984

RESUMEN

Reassortment is an important source of genetic diversity in segmented viruses and is the main source of novel pathogenic influenza viruses. Despite this, studying the reassortment process has been constrained by the lack of a coherent, model-based inference framework. Here, we introduce a coalescent-based model that allows us to explicitly model the joint coalescent and reassortment process. In order to perform inference under this model, we present an efficient Markov chain Monte Carlo algorithm to sample rooted networks and the embedding of phylogenetic trees within networks. This algorithm provides the means to jointly infer coalescent and reassortment rates with the reassortment network and the embedding of segments in that network from full-genome sequence data. Studying reassortment patterns of different human influenza datasets, we find large differences in reassortment rates across different human influenza viruses. Additionally, we find that reassortment events predominantly occur on selectively fitter parts of reassortment networks showing that on a population level, reassortment positively contributes to the fitness of human influenza viruses.


Asunto(s)
Gripe Humana/virología , Modelos Genéticos , Orthomyxoviridae/genética , Virus Reordenados/genética , Algoritmos , Evolución Molecular , Genoma Viral/genética , Humanos , Modelos Estadísticos , Filogenia
11.
Syst Biol ; 71(1): 208-220, 2021 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-34228807

RESUMEN

Evolutionary models account for either population- or species-level processes but usually not both. We introduce a new model, the FBD-MSC, which makes it possible for the first time to integrate both the genealogical and fossilization phenomena, by means of the multispecies coalescent (MSC) and the fossilized birth-death (FBD) processes. Using this model, we reconstruct the phylogeny representing all extant and many fossil Caninae, recovering both the relative and absolute time of speciation events. We quantify known inaccuracy issues with divergence time estimates using the popular strategy of concatenating molecular alignments and show that the FBD-MSC solves them. Our new integrative method and empirical results advance the paradigm and practice of probabilistic total evidence analyses in evolutionary biology.[Caninae; fossilized birth-death; molecular clock; multispecies coalescent; phylogenetics; species trees.].


Asunto(s)
Especiación Genética , Modelos Biológicos , Evolución Biológica , Fósiles , Filogenia
12.
Syst Biol ; 69(5): 973-986, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32105322

RESUMEN

Heterogeneous populations can lead to important differences in birth and death rates across a phylogeny. Taking this heterogeneity into account is necessary to obtain accurate estimates of the underlying population dynamics. We present a new multitype birth-death model (MTBD) that can estimate lineage-specific birth and death rates. This corresponds to estimating lineage-dependent speciation and extinction rates for species phylogenies, and lineage-dependent transmission and recovery rates for pathogen transmission trees. In contrast with previous models, we do not presume to know the trait driving the rate differences, nor do we prohibit the same rates from appearing in different parts of the phylogeny. Using simulated data sets, we show that the MTBD model can reliably infer the presence of multiple evolutionary regimes, their positions in the tree, and the birth and death rates associated with each. We also present a reanalysis of two empirical data sets and compare the results obtained by MTBD and by the existing software BAMM. We compare two implementations of the model, one exact and one approximate (assuming that no rate changes occur in the extinct parts of the tree), and show that the approximation only slightly affects results. The MTBD model is implemented as a package in the Bayesian inference software BEAST 2 and allows joint inference of the phylogeny and the model parameters.[Birth-death; lineage specific rates, multi-type model.].


Asunto(s)
Tasa de Natalidad , Clasificación/métodos , Modelos Biológicos , Mortalidad , Teorema de Bayes , Simulación por Computador , Filogenia , Programas Informáticos
13.
Mol Biol Evol ; 36(8): 1804-1816, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31058982

RESUMEN

Modern phylodynamic methods interpret an inferred phylogenetic tree as a partial transmission chain providing information about the dynamic process of transmission and removal (where removal may be due to recovery, death, or behavior change). Birth-death and coalescent processes have been introduced to model the stochastic dynamics of epidemic spread under common epidemiological models such as the SIS and SIR models and are successfully used to infer phylogenetic trees together with transmission (birth) and removal (death) rates. These methods either integrate analytically over past incidence and prevalence to infer rate parameters, and thus cannot explicitly infer past incidence or prevalence, or allow such inference only in the coalescent limit of large population size. Here, we introduce a particle filtering framework to explicitly infer prevalence and incidence trajectories along with phylogenies and epidemiological model parameters from genomic sequences and case count data in a manner consistent with the underlying birth-death model. After demonstrating the accuracy of this method on simulated data, we use it to assess the prevalence through time of the early 2014 Ebola outbreak in Sierra Leone.


Asunto(s)
Genómica/métodos , Incidencia , Epidemiología Molecular/métodos , Prevalencia , Teorema de Bayes , Fiebre Hemorrágica Ebola/epidemiología , Humanos , Sierra Leona/epidemiología
14.
PLoS Comput Biol ; 15(4): e1006650, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30958812

RESUMEN

Elaboration of Bayesian phylogenetic inference methods has continued at pace in recent years with major new advances in nearly all aspects of the joint modelling of evolutionary data. It is increasingly appreciated that some evolutionary questions can only be adequately answered by combining evidence from multiple independent sources of data, including genome sequences, sampling dates, phenotypic data, radiocarbon dates, fossil occurrences, and biogeographic range information among others. Including all relevant data into a single joint model is very challenging both conceptually and computationally. Advanced computational software packages that allow robust development of compatible (sub-)models which can be composed into a full model hierarchy have played a key role in these developments. Developing such software frameworks is increasingly a major scientific activity in its own right, and comes with specific challenges, from practical software design, development and engineering challenges to statistical and conceptual modelling challenges. BEAST 2 is one such computational software platform, and was first announced over 4 years ago. Here we describe a series of major new developments in the BEAST 2 core platform and model hierarchy that have occurred since the first release of the software, culminating in the recent 2.5 release.


Asunto(s)
Teorema de Bayes , Evolución Biológica , Filogenia , Programas Informáticos , Animales , Biología Computacional , Simulación por Computador , Evolución Molecular , Humanos , Cadenas de Markov , Modelos Genéticos , Método de Montecarlo
15.
Syst Biol ; 67(1): 170-174, 2018 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-28673048

RESUMEN

Phylogenetics and phylodynamics are central topics in modern evolutionary biology. Phylogenetic methods reconstruct the evolutionary relationships among organisms, whereas phylodynamic approaches reveal the underlying diversification processes that lead to the observed relationships. These two fields have many practical applications in disciplines as diverse as epidemiology, developmental biology, palaeontology, ecology, and linguistics. The combination of increasingly large genetic data sets and increases in computing power is facilitating the development of more sophisticated phylogenetic and phylodynamic methods. Big data sets allow us to answer complex questions. However, since the required analyses are highly specific to the particular data set and question, a black-box method is not sufficient anymore. Instead, biologists are required to be actively involved with modeling decisions during data analysis. The modular design of the Bayesian phylogenetic software package BEAST 2 enables, and in fact enforces, this involvement. At the same time, the modular design enables computational biology groups to develop new methods at a rapid rate. A thorough understanding of the models and algorithms used by inference software is a critical prerequisite for successful hypothesis formulation and assessment. In particular, there is a need for more readily available resources aimed at helping interested scientists equip themselves with the skills to confidently use cutting-edge phylogenetic analysis software. These resources will also benefit researchers who do not have access to similar courses or training at their home institutions. Here, we introduce the "Taming the Beast" (https://taming-the-beast.github.io/) resource, which was developed as part of a workshop series bearing the same name, to facilitate the usage of the Bayesian phylogenetic software package BEAST 2.


Asunto(s)
Biología Computacional/educación , Biología Computacional/métodos , Filogenia , Programas Informáticos , Materiales de Enseñanza , Algoritmos
16.
Bioinformatics ; 33(15): 2392-2394, 2017 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-28407035

RESUMEN

SUMMARY: IcyTree is an easy-to-use application which can be used to visualize a wide variety of phylogenetic trees and networks. While numerous phylogenetic tree viewers exist already, IcyTree distinguishes itself by being a purely online tool, having a responsive user interface, supporting phylogenetic networks (ancestral recombination graphs in particular), and efficiently drawing trees that include information such as ancestral locations or trait values. IcyTree also provides intuitive panning and zooming utilities that make exploring large phylogenetic trees of many thousands of taxa feasible. AVAILABILITY AND IMPLEMENTATION: IcyTree is a web application and can be accessed directly at http://tgvaughan.github.com/icytree . Currently supported web browsers include Mozilla Firefox and Google Chrome. IcyTree is written entirely in client-side JavaScript (no plugin required) and, once loaded, does not require network access to run. IcyTree is free software, and the source code is made available at http://github.com/tgvaughan/icytree under version 3 of the GNU General Public License. CONTACT: tgvaughan@gmail.com.


Asunto(s)
Genómica/métodos , Filogenia , Programas Informáticos , Internet , Orthomyxoviridae/genética
17.
Mol Biol Evol ; 33(8): 2102-16, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27189573

RESUMEN

When viruses spread, outbreaks can be spawned in previously unaffected regions. Depending on the time and mode of introduction, each regional outbreak can have its own epidemic dynamics. The migration and phylodynamic processes are often intertwined and need to be taken into account when analyzing temporally and spatially structured virus data. In this article, we present a fully probabilistic approach for the joint reconstruction of phylodynamic history in structured populations (such as geographic structure) based on a multitype birth-death process. This approach can be used to quantify the spread of a pathogen in a structured population. Changes in epidemic dynamics through time within subpopulations are incorporated through piecewise constant changes in transmission parameters.We analyze a global human influenza H3N2 virus data set from a geographically structured host population to demonstrate how seasonal dynamics can be inferred simultaneously with the phylogeny and migration process. Our results suggest that the main migration path among the northern, tropical, and southern region represented in the sample analyzed here is the one leading from the tropics to the northern region. Furthermore, the time-dependent transmission dynamics between and within two HIV risk groups, heterosexuals and injecting drug users, in the Latvian HIV epidemic are investigated. Our analyses confirm that the Latvian HIV epidemic peaking around 2001 was mainly driven by the injecting drug user risk group.


Asunto(s)
Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Gripe Humana/virología , Teorema de Bayes , Simulación por Computador , Brotes de Enfermedades , Epidemias , Genómica/métodos , Humanos , Subtipo H3N2 del Virus de la Influenza A/genética , Gripe Humana/transmisión , Filogenia , Filogeografía/métodos
18.
Clin Infect Dis ; 61 Suppl 4: S259-65, 2015 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-26449940

RESUMEN

Nontyphoidal Salmonella (NTS) is a frequent cause of diarrhea around the world, yet in many African countries it is more commonly associated with invasive bacterial disease. Various source attribution models have been developed that utilize microbial subtyping data to assign cases of human NTS infection to different animal populations and foods of animal origin. Advances in molecular microbial subtyping approaches, in particular whole-genome sequencing, provide higher resolution data with which to investigate these sources. In this review, we provide updates on the source attribution models developed for Salmonella, and examine the application of whole-genome sequencing data combined with evolutionary modeling to investigate the putative sources and transmission pathways of NTS, with a focus on the epidemiology of NTS in Africa. This is essential information to decide where, what, and how control strategies might be applied most effectively.


Asunto(s)
Infecciones por Salmonella/microbiología , Infecciones por Salmonella/transmisión , Salmonella enterica/genética , África/epidemiología , Animales , Bacteriemia/microbiología , Bacteriemia/transmisión , Evolución Molecular , Genoma Bacteriano , Humanos , Modelos Biológicos , Infecciones por Salmonella/epidemiología , Salmonella enterica/clasificación , Salmonella enterica/aislamiento & purificación , Salmonella enterica/patogenicidad , Análisis de Secuencia de ADN
19.
Proc Biol Sci ; 282(1806): 20150420, 2015 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-25876846

RESUMEN

One of the central objectives in the field of phylodynamics is the quantification of population dynamic processes using genetic sequence data or in some cases phenotypic data. Phylodynamics has been successfully applied to many different processes, such as the spread of infectious diseases, within-host evolution of a pathogen, macroevolution and even language evolution. Phylodynamic analysis requires a probability distribution on phylogenetic trees spanned by the genetic data. Because such a probability distribution is not available for many common stochastic population dynamic processes, coalescent-based approximations assuming deterministic population size changes are widely employed. Key to many population dynamic models, in particular epidemiological models, is a period of exponential population growth during the initial phase. Here, we show that the coalescent does not well approximate stochastic exponential population growth, which is typically modelled by a birth-death process. We demonstrate that introducing demographic stochasticity into the population size function of the coalescent improves the approximation for values of R0 close to 1, but substantial differences remain for large R0. In addition, the computational advantage of using an approximation over exact models vanishes when introducing such demographic stochasticity. These results highlight that we need to increase efforts to develop phylodynamic tools that correctly account for the stochasticity of population dynamic models for inference.


Asunto(s)
Tasa de Natalidad , Modelos Biológicos , Mortalidad , Dinámica Poblacional , Crecimiento Demográfico , Procesos Estocásticos
20.
Bioinformatics ; 30(16): 2272-9, 2014 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-24753484

RESUMEN

MOTIVATION: Population structure significantly affects evolutionary dynamics. Such structure may be due to spatial segregation, but may also reflect any other gene-flow-limiting aspect of a model. In combination with the structured coalescent, this fact can be used to inform phylogenetic tree reconstruction, as well as to infer parameters such as migration rates and subpopulation sizes from annotated sequence data. However, conducting Bayesian inference under the structured coalescent is impeded by the difficulty of constructing Markov Chain Monte Carlo (MCMC) sampling algorithms (samplers) capable of efficiently exploring the state space. RESULTS: In this article, we present a new MCMC sampler capable of sampling from posterior distributions over structured trees: timed phylogenetic trees in which lineages are associated with the distinct subpopulation in which they lie. The sampler includes a set of MCMC proposal functions that offer significant mixing improvements over a previously published method. Furthermore, its implementation as a BEAST 2 package ensures maximum flexibility with respect to model and prior specification. We demonstrate the usefulness of this new sampler by using it to infer migration rates and effective population sizes of H3N2 influenza between New Zealand, New York and Hong Kong from publicly available hemagglutinin (HA) gene sequences under the structured coalescent. AVAILABILITY AND IMPLEMENTATION: The sampler has been implemented as a publicly available BEAST 2 package that is distributed under version 3 of the GNU General Public License at http://compevol.github.io/MultiTypeTree.


Asunto(s)
Filogenia , Algoritmos , Teorema de Bayes , Subtipo H3N2 del Virus de la Influenza A/genética , Cadenas de Markov , Método de Montecarlo , Tasa de Mutación
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