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    Identity-by-descent analyses for measuring population dynamics and selection in recombining pathogens

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    Author
    Henden, L; Lee, S; Mueller, I; Barry, A; Bahlo, M
    Date
    2018-05-01
    Source Title
    PLoS Genetics
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Barry, Alyssa; Mueller, Ivo; Bahlo, Melanie; Henden, Lyndal
    Affiliation
    Medical Biology (W.E.H.I.)
    School of Mathematics and Statistics
    Metadata
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    Document Type
    Journal Article
    Citations
    Henden, L., Lee, S., Mueller, I., Barry, A. & Bahlo, M. (2018). Identity-by-descent analyses for measuring population dynamics and selection in recombining pathogens. PLOS GENETICS, 14 (5), https://doi.org/10.1371/journal.pgen.1007279.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255227
    DOI
    10.1371/journal.pgen.1007279
    Abstract
    Identification of genomic regions that are identical by descent (IBD) has proven useful for human genetic studies where analyses have led to the discovery of familial relatedness and fine-mapping of disease critical regions. Unfortunately however, IBD analyses have been underutilized in analysis of other organisms, including human pathogens. This is in part due to the lack of statistical methodologies for non-diploid genomes in addition to the added complexity of multiclonal infections. As such, we have developed an IBD methodology, called isoRelate, for analysis of haploid recombining microorganisms in the presence of multiclonal infections. Using the inferred IBD status at genomic locations, we have also developed a novel statistic for identifying loci under positive selection and propose relatedness networks as a means of exploring shared haplotypes within populations. We evaluate the performance of our methodologies for detecting IBD and selection, including comparisons with existing tools, then perform an exploratory analysis of whole genome sequencing data from a global Plasmodium falciparum dataset of more than 2500 genomes. This analysis identifies Southeast Asia as having many highly related isolates, possibly as a result of both reduced transmission from intensified control efforts and population bottlenecks following the emergence of antimalarial drug resistance. Many signals of selection are also identified, most of which overlap genes that are known to be associated with drug resistance, in addition to two novel signals observed in multiple countries that have yet to be explored in detail. Additionally, we investigate relatedness networks over the selected loci and determine that one of these sweeps has spread between continents while the other has arisen independently in different countries. IBD analysis of microorganisms using isoRelate can be used for exploring population structure, positive selection and haplotype distributions, and will be a valuable tool for monitoring disease control and elimination efforts of many diseases.

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