Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes
Identifieur interne : 001781 ( Ncbi/Merge ); précédent : 001780; suivant : 001782Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes
Auteurs : John A. Lees [Royaume-Uni] ; Minna Vehkala [Finlande] ; Niko V Lim Ki [Finlande] ; Simon R. Harris [Royaume-Uni] ; Claire Chewapreecha [Royaume-Uni] ; Nicholas J. Croucher [Royaume-Uni] ; Pekka Marttinen [Finlande] ; Mark R. Davies [Australie] ; Andrew C. Steer [Australie] ; Steven Y. C. Tong [Australie] ; Antti Honkela [Finlande] ; Julian Parkhill [Royaume-Uni] ; Stephen D. Bentley [Royaume-Uni] ; Jukka Corander [Royaume-Uni, Finlande, Norvège]Source :
- Nature Communications [ 2041-1723 ] ; 2016.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : DNA, Bacterial.
- genetics : Streptococcus pneumoniae, Streptococcus pyogenes.
- Computer Simulation, Genome, Bacterial, Genome-Wide Association Study, Models, Genetic, Nucleic Acid Amplification Techniques.
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
Url:
DOI: 10.1038/ncomms12797
PubMed: 27633831
PubMed Central: 5028413
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PMC:5028413Le document en format XML
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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, 0317 Oslo,<country>Norway</country>
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<term>Genome, Bacterial</term>
<term>Genome-Wide Association Study</term>
<term>Models, Genetic</term>
<term>Nucleic Acid Amplification Techniques</term>
<term>Streptococcus pneumoniae (genetics)</term>
<term>Streptococcus pyogenes (genetics)</term>
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<term>Simulation numérique</term>
<term>Streptococcus pneumoniae (génétique)</term>
<term>Streptococcus pyogenes (génétique)</term>
<term>Techniques d'amplification d'acides nucléiques</term>
<term>Étude d'association pangénomique</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA, Bacterial</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Streptococcus pneumoniae</term>
<term>Streptococcus pyogenes</term>
</keywords>
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<term>Streptococcus pneumoniae</term>
<term>Streptococcus pyogenes</term>
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<term>Genome, Bacterial</term>
<term>Genome-Wide Association Study</term>
<term>Models, Genetic</term>
<term>Nucleic Acid Amplification Techniques</term>
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<term>Simulation numérique</term>
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<front><div type="abstract" xml:lang="en"><p>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 <italic>Streptococcus pneumoniae</italic>
and <italic>Streptococcus pyogenes</italic>
, SEER identifies relevant previously characterized resistance determinants for several antibiotics and discovers potential novel factors related to the invasiveness of <italic>S. pyogenes</italic>
. We thus demonstrate that our method can answer important biologically and medically relevant questions.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Falush, D" uniqKey="Falush D">D. Falush</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chen, P E" uniqKey="Chen P">P. E. Chen</name>
</author>
<author><name sortKey="Shapiro, B J" uniqKey="Shapiro B">B. J. Shapiro</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Farhat, M R" uniqKey="Farhat M">M. R. Farhat</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liu, J Z" uniqKey="Liu J">J. Z. Liu</name>
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, Cambridge CB10 1SA,<country>UK</country>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Vehkala, Minna" sort="Vehkala, Minna" uniqKey="Vehkala M" first="Minna" last="Vehkala">Minna Vehkala</name>
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</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author><name sortKey="V Lim Ki, Niko" sort="V Lim Ki, Niko" uniqKey="V Lim Ki N" first="Niko" last="V Lim Ki">Niko V Lim Ki</name>
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</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Harris, Simon R" sort="Harris, Simon R" uniqKey="Harris S" first="Simon R." last="Harris">Simon R. Harris</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Chewapreecha, Claire" sort="Chewapreecha, Claire" uniqKey="Chewapreecha C" first="Claire" last="Chewapreecha">Claire Chewapreecha</name>
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, Cambridge CB2 0SP,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author><name sortKey="Croucher, Nicholas J" sort="Croucher, Nicholas J" uniqKey="Croucher N" first="Nicholas J." last="Croucher">Nicholas J. Croucher</name>
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, London W2 1NY,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Marttinen, Pekka" sort="Marttinen, Pekka" uniqKey="Marttinen P" first="Pekka" last="Marttinen">Pekka Marttinen</name>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Department of Computer Science, Aalto University</institution>
, Espoo FI-00076,<country>Finland</country>
</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="a7"><institution>Helsinki Institute of Information Technology HIIT, Department of Computer Science, Aalto University</institution>
, Espoo FI-00076,<country>Finland</country>
</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Davies, Mark R" sort="Davies, Mark R" uniqKey="Davies M" first="Mark R." last="Davies">Mark R. Davies</name>
<affiliation wicri:level="1"><nlm:aff id="a8"><institution>Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne</institution>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Steer, Andrew C" sort="Steer, Andrew C" uniqKey="Steer A" first="Andrew C." last="Steer">Andrew C. Steer</name>
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, Melbourne, Victoria 3052,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a10"><institution>Group A Streptococcal Research Group, Murdoch Children's Research Institute</institution>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Tong, Steven Y C" sort="Tong, Steven Y C" uniqKey="Tong S" first="Steven Y. C." last="Tong">Steven Y. C. Tong</name>
<affiliation wicri:level="1"><nlm:aff id="a11"><institution>Menzies School of Health Research</institution>
, Darwin, Northern Territory 0811,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Honkela, Antti" sort="Honkela, Antti" uniqKey="Honkela A" first="Antti" last="Honkela">Antti Honkela</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki</institution>
, Helsinki FI-00014,<country>Finland</country>
</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Parkhill, Julian" sort="Parkhill, Julian" uniqKey="Parkhill J" first="Julian" last="Parkhill">Julian Parkhill</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Pathogen Genomics, Wellcome Trust Sanger Institute</institution>
, Cambridge CB10 1SA,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bentley, Stephen D" sort="Bentley, Stephen D" uniqKey="Bentley S" first="Stephen D." last="Bentley">Stephen D. Bentley</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Pathogen Genomics, Wellcome Trust Sanger Institute</institution>
, Cambridge CB10 1SA,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Corander, Jukka" sort="Corander, Jukka" uniqKey="Corander J" first="Jukka" last="Corander">Jukka Corander</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Pathogen Genomics, Wellcome Trust Sanger Institute</institution>
, Cambridge CB10 1SA,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Mathematics and Statistics, University of Helsinki</institution>
, Helsinki FI-00014,<country>Finland</country>
</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a13"><institution>Department of Biostatistics, University of Oslo</institution>
, 0317 Oslo,<country>Norway</country>
</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<idno type="doi">10.1038/ncomms12797</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes</title>
<author><name sortKey="Lees, John A" sort="Lees, John A" uniqKey="Lees J" first="John A." last="Lees">John A. Lees</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Pathogen Genomics, Wellcome Trust Sanger Institute</institution>
, Cambridge CB10 1SA,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Vehkala, Minna" sort="Vehkala, Minna" uniqKey="Vehkala M" first="Minna" last="Vehkala">Minna Vehkala</name>
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, Helsinki FI-00014,<country>Finland</country>
</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="V Lim Ki, Niko" sort="V Lim Ki, Niko" uniqKey="V Lim Ki N" first="Niko" last="V Lim Ki">Niko V Lim Ki</name>
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, Helsinki FI-00014,<country>Finland</country>
</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Harris, Simon R" sort="Harris, Simon R" uniqKey="Harris S" first="Simon R." last="Harris">Simon R. Harris</name>
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, Cambridge CB10 1SA,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author><name sortKey="Chewapreecha, Claire" sort="Chewapreecha, Claire" uniqKey="Chewapreecha C" first="Claire" last="Chewapreecha">Claire Chewapreecha</name>
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, Cambridge CB2 0SP,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Croucher, Nicholas J" sort="Croucher, Nicholas J" uniqKey="Croucher N" first="Nicholas J." last="Croucher">Nicholas J. Croucher</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Infectious Disease Epidemiology, Imperial College</institution>
, London W2 1NY,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Marttinen, Pekka" sort="Marttinen, Pekka" uniqKey="Marttinen P" first="Pekka" last="Marttinen">Pekka Marttinen</name>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Department of Computer Science, Aalto University</institution>
, Espoo FI-00076,<country>Finland</country>
</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>Helsinki Institute of Information Technology HIIT, Department of Computer Science, Aalto University</institution>
, Espoo FI-00076,<country>Finland</country>
</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Davies, Mark R" sort="Davies, Mark R" uniqKey="Davies M" first="Mark R." last="Davies">Mark R. Davies</name>
<affiliation wicri:level="1"><nlm:aff id="a8"><institution>Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne</institution>
, Melbourne, Victoria 3010,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Steer, Andrew C" sort="Steer, Andrew C" uniqKey="Steer A" first="Andrew C." last="Steer">Andrew C. Steer</name>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Centre for International Child Health, Department of Paediatrics, University of Melbourne</institution>
, Melbourne, Victoria 3052,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a10"><institution>Group A Streptococcal Research Group, Murdoch Children's Research Institute</institution>
, Parkville, Victoria 3052,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tong, Steven Y C" sort="Tong, Steven Y C" uniqKey="Tong S" first="Steven Y. C." last="Tong">Steven Y. C. Tong</name>
<affiliation wicri:level="1"><nlm:aff id="a11"><institution>Menzies School of Health Research</institution>
, Darwin, Northern Territory 0811,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Honkela, Antti" sort="Honkela, Antti" uniqKey="Honkela A" first="Antti" last="Honkela">Antti Honkela</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki</institution>
, Helsinki FI-00014,<country>Finland</country>
</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Parkhill, Julian" sort="Parkhill, Julian" uniqKey="Parkhill J" first="Julian" last="Parkhill">Julian Parkhill</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Pathogen Genomics, Wellcome Trust Sanger Institute</institution>
, Cambridge CB10 1SA,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bentley, Stephen D" sort="Bentley, Stephen D" uniqKey="Bentley S" first="Stephen D." last="Bentley">Stephen D. Bentley</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Pathogen Genomics, Wellcome Trust Sanger Institute</institution>
, Cambridge CB10 1SA,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Corander, Jukka" sort="Corander, Jukka" uniqKey="Corander J" first="Jukka" last="Corander">Jukka Corander</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Pathogen Genomics, Wellcome Trust Sanger Institute</institution>
, Cambridge CB10 1SA,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Mathematics and Statistics, University of Helsinki</institution>
, Helsinki FI-00014,<country>Finland</country>
</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a13"><institution>Department of Biostatistics, University of Oslo</institution>
, 0317 Oslo,<country>Norway</country>
</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>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 <italic>Streptococcus pneumoniae</italic>
and <italic>Streptococcus pyogenes</italic>
, SEER identifies relevant previously characterized resistance determinants for several antibiotics and discovers potential novel factors related to the invasiveness of <italic>S. pyogenes</italic>
. We thus demonstrate that our method can answer important biologically and medically relevant questions.</p>
</div>
</front>
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</listBibl>
</div1>
</back>
</TEI>
</pmc>
<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes.</title>
<author><name sortKey="Lees, John A" sort="Lees, John A" uniqKey="Lees J" first="John A" last="Lees">John A. Lees</name>
<affiliation wicri:level="1"><nlm:affiliation>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA</wicri:regionArea>
<wicri:noRegion>Cambridge CB10 1SA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Vehkala, Minna" sort="Vehkala, Minna" uniqKey="Vehkala M" first="Minna" last="Vehkala">Minna Vehkala</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Mathematics and Statistics, University of Helsinki, Helsinki FI-00014, Finland.</nlm:affiliation>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Department of Mathematics and Statistics, University of Helsinki, Helsinki FI-00014</wicri:regionArea>
<orgName type="university">Université d'Helsinki</orgName>
<placeName><settlement type="city">Helsinki</settlement>
<region type="région" nuts="2">Uusimaa</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="V Lim Ki, Niko" sort="V Lim Ki, Niko" uniqKey="V Lim Ki N" first="Niko" last="V Lim Ki">Niko V Lim Ki</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Medical and Clinical Genetics, Genome-Scale Biology Research Program, University of Helsinki, Helsinki FI-00014, Finland.</nlm:affiliation>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Department of Medical and Clinical Genetics, Genome-Scale Biology Research Program, University of Helsinki, Helsinki FI-00014</wicri:regionArea>
<orgName type="university">Université d'Helsinki</orgName>
<placeName><settlement type="city">Helsinki</settlement>
<region type="région" nuts="2">Uusimaa</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Harris, Simon R" sort="Harris, Simon R" uniqKey="Harris S" first="Simon R" last="Harris">Simon R. Harris</name>
<affiliation wicri:level="1"><nlm:affiliation>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA</wicri:regionArea>
<wicri:noRegion>Cambridge CB10 1SA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chewapreecha, Claire" sort="Chewapreecha, Claire" uniqKey="Chewapreecha C" first="Claire" last="Chewapreecha">Claire Chewapreecha</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, University of Cambridge, Cambridge CB2 0SP, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Medicine, University of Cambridge, Cambridge CB2 0SP</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Croucher, Nicholas J" sort="Croucher, Nicholas J" uniqKey="Croucher N" first="Nicholas J" last="Croucher">Nicholas J. Croucher</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Infectious Disease Epidemiology, Imperial College, London W2 1NY, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Infectious Disease Epidemiology, Imperial College, London W2 1NY</wicri:regionArea>
<wicri:noRegion>London W2 1NY</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Marttinen, Pekka" sort="Marttinen, Pekka" uniqKey="Marttinen P" first="Pekka" last="Marttinen">Pekka Marttinen</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Computer Science, Aalto University, Espoo FI-00076, Finland.</nlm:affiliation>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Department of Computer Science, Aalto University, Espoo FI-00076</wicri:regionArea>
<orgName type="university">Université Aalto</orgName>
<placeName><settlement type="city">Espoo</settlement>
<region type="région" nuts="2">Uusimaa</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Davies, Mark R" sort="Davies, Mark R" uniqKey="Davies M" first="Mark R" last="Davies">Mark R. Davies</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Steer, Andrew C" sort="Steer, Andrew C" uniqKey="Steer A" first="Andrew C" last="Steer">Andrew C. Steer</name>
<affiliation wicri:level="4"><nlm:affiliation>Centre for International Child Health, Department of Paediatrics, University of Melbourne, Melbourne, Victoria 3052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for International Child Health, Department of Paediatrics, University of Melbourne, Melbourne, Victoria 3052</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tong, Steven Y C" sort="Tong, Steven Y C" uniqKey="Tong S" first="Steven Y C" last="Tong">Steven Y C. Tong</name>
<affiliation wicri:level="1"><nlm:affiliation>Menzies School of Health Research, Darwin, Northern Territory 0811, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Menzies School of Health Research, Darwin, Northern Territory 0811</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Honkela, Antti" sort="Honkela, Antti" uniqKey="Honkela A" first="Antti" last="Honkela">Antti Honkela</name>
<affiliation wicri:level="4"><nlm:affiliation>Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Helsinki FI-00014, Finland.</nlm:affiliation>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Helsinki FI-00014</wicri:regionArea>
<orgName type="university">Université d'Helsinki</orgName>
<placeName><settlement type="city">Helsinki</settlement>
<region type="région" nuts="2">Uusimaa</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Parkhill, Julian" sort="Parkhill, Julian" uniqKey="Parkhill J" first="Julian" last="Parkhill">Julian Parkhill</name>
<affiliation wicri:level="1"><nlm:affiliation>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA</wicri:regionArea>
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</author>
<author><name sortKey="Bentley, Stephen D" sort="Bentley, Stephen D" uniqKey="Bentley S" first="Stephen D" last="Bentley">Stephen D. Bentley</name>
<affiliation wicri:level="1"><nlm:affiliation>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA</wicri:regionArea>
<wicri:noRegion>Cambridge CB10 1SA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Corander, Jukka" sort="Corander, Jukka" uniqKey="Corander J" first="Jukka" last="Corander">Jukka Corander</name>
<affiliation wicri:level="1"><nlm:affiliation>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA</wicri:regionArea>
<wicri:noRegion>Cambridge CB10 1SA</wicri:noRegion>
</affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes.</title>
<author><name sortKey="Lees, John A" sort="Lees, John A" uniqKey="Lees J" first="John A" last="Lees">John A. Lees</name>
<affiliation wicri:level="1"><nlm:affiliation>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA</wicri:regionArea>
<wicri:noRegion>Cambridge CB10 1SA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Vehkala, Minna" sort="Vehkala, Minna" uniqKey="Vehkala M" first="Minna" last="Vehkala">Minna Vehkala</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Mathematics and Statistics, University of Helsinki, Helsinki FI-00014, Finland.</nlm:affiliation>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Department of Mathematics and Statistics, University of Helsinki, Helsinki FI-00014</wicri:regionArea>
<orgName type="university">Université d'Helsinki</orgName>
<placeName><settlement type="city">Helsinki</settlement>
<region type="région" nuts="2">Uusimaa</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="V Lim Ki, Niko" sort="V Lim Ki, Niko" uniqKey="V Lim Ki N" first="Niko" last="V Lim Ki">Niko V Lim Ki</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Medical and Clinical Genetics, Genome-Scale Biology Research Program, University of Helsinki, Helsinki FI-00014, Finland.</nlm:affiliation>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Department of Medical and Clinical Genetics, Genome-Scale Biology Research Program, University of Helsinki, Helsinki FI-00014</wicri:regionArea>
<orgName type="university">Université d'Helsinki</orgName>
<placeName><settlement type="city">Helsinki</settlement>
<region type="région" nuts="2">Uusimaa</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Harris, Simon R" sort="Harris, Simon R" uniqKey="Harris S" first="Simon R" last="Harris">Simon R. Harris</name>
<affiliation wicri:level="1"><nlm:affiliation>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA</wicri:regionArea>
<wicri:noRegion>Cambridge CB10 1SA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chewapreecha, Claire" sort="Chewapreecha, Claire" uniqKey="Chewapreecha C" first="Claire" last="Chewapreecha">Claire Chewapreecha</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, University of Cambridge, Cambridge CB2 0SP, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Medicine, University of Cambridge, Cambridge CB2 0SP</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Croucher, Nicholas J" sort="Croucher, Nicholas J" uniqKey="Croucher N" first="Nicholas J" last="Croucher">Nicholas J. Croucher</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Infectious Disease Epidemiology, Imperial College, London W2 1NY, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Infectious Disease Epidemiology, Imperial College, London W2 1NY</wicri:regionArea>
<wicri:noRegion>London W2 1NY</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Marttinen, Pekka" sort="Marttinen, Pekka" uniqKey="Marttinen P" first="Pekka" last="Marttinen">Pekka Marttinen</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Computer Science, Aalto University, Espoo FI-00076, Finland.</nlm:affiliation>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Department of Computer Science, Aalto University, Espoo FI-00076</wicri:regionArea>
<orgName type="university">Université Aalto</orgName>
<placeName><settlement type="city">Espoo</settlement>
<region type="région" nuts="2">Uusimaa</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Davies, Mark R" sort="Davies, Mark R" uniqKey="Davies M" first="Mark R" last="Davies">Mark R. Davies</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Steer, Andrew C" sort="Steer, Andrew C" uniqKey="Steer A" first="Andrew C" last="Steer">Andrew C. Steer</name>
<affiliation wicri:level="4"><nlm:affiliation>Centre for International Child Health, Department of Paediatrics, University of Melbourne, Melbourne, Victoria 3052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for International Child Health, Department of Paediatrics, University of Melbourne, Melbourne, Victoria 3052</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tong, Steven Y C" sort="Tong, Steven Y C" uniqKey="Tong S" first="Steven Y C" last="Tong">Steven Y C. Tong</name>
<affiliation wicri:level="1"><nlm:affiliation>Menzies School of Health Research, Darwin, Northern Territory 0811, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Menzies School of Health Research, Darwin, Northern Territory 0811</wicri:regionArea>
<wicri:noRegion>Northern Territory 0811</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Honkela, Antti" sort="Honkela, Antti" uniqKey="Honkela A" first="Antti" last="Honkela">Antti Honkela</name>
<affiliation wicri:level="4"><nlm:affiliation>Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Helsinki FI-00014, Finland.</nlm:affiliation>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Helsinki FI-00014</wicri:regionArea>
<orgName type="university">Université d'Helsinki</orgName>
<placeName><settlement type="city">Helsinki</settlement>
<region type="région" nuts="2">Uusimaa</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Parkhill, Julian" sort="Parkhill, Julian" uniqKey="Parkhill J" first="Julian" last="Parkhill">Julian Parkhill</name>
<affiliation wicri:level="1"><nlm:affiliation>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA</wicri:regionArea>
<wicri:noRegion>Cambridge CB10 1SA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bentley, Stephen D" sort="Bentley, Stephen D" uniqKey="Bentley S" first="Stephen D" last="Bentley">Stephen D. Bentley</name>
<affiliation wicri:level="1"><nlm:affiliation>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA</wicri:regionArea>
<wicri:noRegion>Cambridge CB10 1SA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Corander, Jukka" sort="Corander, Jukka" uniqKey="Corander J" first="Jukka" last="Corander">Jukka Corander</name>
<affiliation wicri:level="1"><nlm:affiliation>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA</wicri:regionArea>
<wicri:noRegion>Cambridge CB10 1SA</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2016" type="published">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Computer Simulation</term>
<term>DNA, Bacterial (genetics)</term>
<term>Genome, Bacterial</term>
<term>Genome-Wide Association Study</term>
<term>Models, Genetic</term>
<term>Nucleic Acid Amplification Techniques</term>
<term>Streptococcus pneumoniae (genetics)</term>
<term>Streptococcus pyogenes (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ADN bactérien (génétique)</term>
<term>Génome bactérien</term>
<term>Modèles génétiques</term>
<term>Simulation numérique</term>
<term>Streptococcus pneumoniae (génétique)</term>
<term>Streptococcus pyogenes (génétique)</term>
<term>Techniques d'amplification d'acides nucléiques</term>
<term>Étude d'association pangénomique</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA, Bacterial</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Streptococcus pneumoniae</term>
<term>Streptococcus pyogenes</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ADN bactérien</term>
<term>Streptococcus pneumoniae</term>
<term>Streptococcus pyogenes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Computer Simulation</term>
<term>Genome, Bacterial</term>
<term>Genome-Wide Association Study</term>
<term>Models, Genetic</term>
<term>Nucleic Acid Amplification Techniques</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Génome bactérien</term>
<term>Modèles génétiques</term>
<term>Simulation numérique</term>
<term>Techniques d'amplification d'acides nucléiques</term>
<term>Étude d'association pangénomique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">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.</div>
</front>
</TEI>
</pubmed>
</double>
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