Dataset Information

Inferring Ancestral Recombination Graphs from Bacterial Genomic Data.

ABSTRACT: Homologous recombination is a central feature of bacterial evolution, yet it confounds traditional phylogenetic methods. While a number of methods specific to bacterial evolution have been developed, none of these permit joint inference of a bacterial recombination graph and associated parameters. In this article, we present a new method which addresses this shortcoming. Our method uses a novel Markov chain Monte Carlo algorithm to perform phylogenetic inference under the ClonalOrigin model. We demonstrate the utility of our method by applying it to ribosomal multilocus sequence typing data sequenced from pathogenic and nonpathogenic Escherichia coli serotype O157 and O26 isolates collected in rural New Zealand. The method is implemented as an open source BEAST 2 package, Bacter, which is available via the project web page at http://tgvaughan.github.io/bacter.

SUBMITTER: Vaughan TG

PROVIDER: S-EPMC5289856 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Publications

Inferring Ancestral Recombination Graphs from Bacterial Genomic Data.

Vaughan Timothy G TG Welch David D Drummond Alexei J AJ Biggs Patrick J PJ George Tessy T French Nigel P NP

Genetics 20161222 2

Homologous recombination is a central feature of bacterial evolution, yet it confounds traditional phylogenetic methods. While a number of methods specific to bacterial evolution have been developed, none of these permit joint inference of a bacterial recombination graph and associated parameters. In this article, we present a new method which addresses this shortcoming. Our method uses a novel Markov chain Monte Carlo algorithm to perform phylogenetic inference under the ClonalOrigin model. We ...[more]

PMID: 28007885

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Project description:The complex correlation structure of a collection of orthologous DNA sequences is uniquely captured by the "ancestral recombination graph" (ARG), a complete record of coalescence and recombination events in the history of the sample. However, existing methods for ARG inference are computationally intensive, highly approximate, or limited to small numbers of sequences, and, as a consequence, explicit ARG inference is rarely used in applied population genomics. Here, we introduce a new algorithm for ARG inference that is efficient enough to apply to dozens of complete mammalian genomes. The key idea of our approach is to sample an ARG of [Formula: see text] chromosomes conditional on an ARG of [Formula: see text] chromosomes, an operation we call "threading." Using techniques based on hidden Markov models, we can perform this threading operation exactly, up to the assumptions of the sequentially Markov coalescent and a discretization of time. An extension allows for threading of subtrees instead of individual sequences. Repeated application of these threading operations results in highly efficient Markov chain Monte Carlo samplers for ARGs. We have implemented these methods in a computer program called ARGweaver. Experiments with simulated data indicate that ARGweaver converges rapidly to the posterior distribution over ARGs and is effective in recovering various features of the ARG for dozens of sequences generated under realistic parameters for human populations. In applications of ARGweaver to 54 human genome sequences from Complete Genomics, we find clear signatures of natural selection, including regions of unusually ancient ancestry associated with balancing selection and reductions in allele age in sites under directional selection. The patterns we observe near protein-coding genes are consistent with a primary influence from background selection rather than hitchhiking, although we cannot rule out a contribution from recurrent selective sweeps.

Dataset Information

Inferring Ancestral Recombination Graphs from Bacterial Genomic Data.

Publications

Inferring Ancestral Recombination Graphs from Bacterial Genomic Data.

Similar Datasets

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