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dc.contributor.authorKachroo, Priyanka
dc.contributor.authorEraso, Jesus M
dc.contributor.authorBeres, Stephen B
dc.contributor.authorOlsen, Randall J
dc.contributor.authorZhu, Luchang
dc.contributor.authorNasser, Waleed
dc.contributor.authorBernard, Paul E
dc.contributor.authorCantu, Concepcion C
dc.contributor.authorSaavedra, Matthew Ojeda
dc.contributor.authorArredondo, María José
dc.contributor.authorStrope, Benjamin
dc.contributor.authorDo, Hackwon
dc.contributor.authorKumaraswami, Muthiah
dc.contributor.authorVuopio, Jaana
dc.contributor.authorGröndahl-Yli-Hannuksela, Kirsi
dc.contributor.authorKristinsson, Karl G
dc.contributor.authorGottfredsson, Magnus
dc.contributor.authorPesonen, Maiju
dc.contributor.authorPensar, Johan
dc.contributor.authorDavenport, Emily R
dc.contributor.authorClark, Andrew G
dc.contributor.authorCorander, Jukka
dc.contributor.authorCaugant, Dominique A
dc.contributor.authorGaini, Shahin
dc.contributor.authorMagnussen, Marita Debess
dc.contributor.authorKubiak, Samantha L
dc.contributor.authorNguyen, Hoang A T
dc.contributor.authorLong, S Wesley
dc.contributor.authorPorter, Adeline R
dc.contributor.authorDeLeo, Frank R
dc.contributor.authorMusser, James M
dc.date.accessioned2019-05-20T15:08:00Z
dc.date.available2019-05-20T15:08:00Z
dc.date.issued2019-03
dc.date.submitted2019-05
dc.identifier.citationIntegrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis. 2019, 51(3):548-559 Nat Geneten_US
dc.identifier.issn1546-1718
dc.identifier.pmid30778225
dc.identifier.doi10.1038/s41588-018-0343-1
dc.identifier.urihttp://hdl.handle.net/2336/620909
dc.descriptionTo access publisher's full text version of this article click on the hyperlink belowen_US
dc.description.abstractStreptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. Although a number of large-scale genomic studies of bacterial pathogens have been published, the relationships among the genome, transcriptome, and virulence in large bacterial populations remain poorly understood. We sequenced the genomes of 2,101 emm28 S. pyogenes invasive strains, from which we selected 492 phylogenetically diverse strains for transcriptome analysis and 50 strains for virulence assessment. Data integration provided a novel understanding of the virulence mechanisms of this model organism. Genome-wide association study, expression quantitative trait loci analysis, machine learning, and isogenic mutant strains identified and confirmed a one-nucleotide indel in an intergenic region that significantly alters global transcript profiles and ultimately virulence. The integrative strategy that we used is generally applicable to any microbe and may lead to new therapeutics for many human pathogens.en_US
dc.description.sponsorshipFondren Foundation, Houston Methodist Hospital and Research Institute Academy of Finland European Research Council National Institutes of Health Intramural Research Program of the National Institute of Allergy and Infectious Disease, National Institutes of Healthen_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.urlhttps://www.nature.com/articles/s41588-018-0343-1en_US
dc.subjectGerlaren_US
dc.subjectBakteríusjúkdómaren_US
dc.subject.meshStreptococcus pyogenesen_US
dc.subject.meshGenome-Wide Association Studyen_US
dc.titleIntegrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis.en_US
dc.typeArticleen_US
dc.contributor.department1 Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, TX, USA. 2 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA. 3 Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA. 4 Institute of Biomedicine, Medical Microbiology and Immunology, University of Turku, Turku, Finland. 5 National Institute for Health and Welfare, Helsinki, Finland. 6 Department of Clinical Microbiology, Landspitali University Hospital, Reykjavik, Iceland. 7 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 8 Department of Infectious Diseases, Landspitali University Hospital, Reykjavik, Iceland. 9 Helsinki Institute of Information Technology, Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland. 10 Department of Computer Science, Aalto University, Espoo, Finland. 11 Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA. 12 Department of Biostatistics, University of Oslo, Oslo, Norway. 13 Division for Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway. 14 Medical Department, Infectious Diseases Division, National Hospital of the Faroe Islands, Tórshavn, Denmark. 15 Department of Infectious Diseases, Odense University Hospital, Odense, Denmark. 16 Department of Clinical Research, University of Southern Denmark, Odense, Denmark. 17 Department of Science and Technology, Centre of Health Research, University of the Faroe Islands, Tórshavn, Denmark. 18 Thetis, Food and Environmental Laboratory, Torshavn, Denmark. 19 Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA. 20 Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, TX, USA. JMMusser@houstonmethodist.org. 21 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA. JMMusser@houstonmethodist.org. 22 Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA. JMMusser@houstonmethodist.org.en_US
dc.identifier.journalNature geneticsen_US
dc.rights.accessLandspitali Access - LSH-aðganguren_US
dc.departmentcodeBAC12
dc.departmentcodeTMD12
dc.source.journaltitleNature genetics


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