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    Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes

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    72
    Author
    Lees, JA; Vehkala, M; Valimaki, N; Harris, SR; Chewapreecha, C; Croucher, NJ; Marttinen, P; Davies, MR; Steer, AC; Tong, SYC; ...
    Date
    2016-09-01
    Source Title
    Nature Communications
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Davies, Mark; Steer, Andrew
    Affiliation
    Paediatrics (RCH)
    Microbiology and Immunology
    Metadata
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    Document Type
    Journal Article
    Citations
    Lees, J. A., Vehkala, M., Valimaki, N., Harris, S. R., Chewapreecha, C., Croucher, N. J., Marttinen, P., Davies, M. R., Steer, A. C., Tong, S. Y. C., Honkela, A., Parkhill, J., Bentley, S. D. & Corander, J. (2016). Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes. NATURE COMMUNICATIONS, 7 (1), https://doi.org/10.1038/ncomms12797.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/260268
    DOI
    10.1038/ncomms12797
    Abstract
    Bacterial genomes vary extensively in terms of both gene content and gene sequence. This plasticity hampers the use of traditional SNP-based methods for identifying all genetic associations with phenotypic variation. Here we introduce a computationally scalable and widely applicable statistical method (SEER) for the identification of sequence elements that are significantly enriched in a phenotype of interest. SEER is applicable to tens of thousands of genomes by counting variable-length k-mers using a distributed string-mining algorithm. Robust options are provided for association analysis that also correct for the clonal population structure of bacteria. Using large collections of genomes of the major human pathogens Streptococcus pneumoniae and Streptococcus pyogenes, SEER identifies relevant previously characterized resistance determinants for several antibiotics and discovers potential novel factors related to the invasiveness of S. pyogenes. We thus demonstrate that our method can answer important biologically and medically relevant questions.

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