Whole Genome Sequencing versus Traditional Genotyping for Investigation of a Mycobacterium tuberculosis Outbreak: A Longitudinal Molecular Epidemiological Study
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{"title"=>"Whole Genome Sequencing versus Traditional Genotyping for Investigation of a Mycobacterium tuberculosis Outbreak: A Longitudinal Molecular Epidemiological Study", "type"=>"journal", "authors"=>[{"first_name"=>"Andreas", "last_name"=>"Roetzer", "scopus_author_id"=>"22035999600"}, {"first_name"=>"Roland", "last_name"=>"Diel", "scopus_author_id"=>"6701319986"}, {"first_name"=>"Thomas A.", "last_name"=>"Kohl", "scopus_author_id"=>"35337009700"}, {"first_name"=>"Christian", "last_name"=>"Rückert", "scopus_author_id"=>"35550975000"}, {"first_name"=>"Ulrich", "last_name"=>"Nübel", "scopus_author_id"=>"6603414263"}, {"first_name"=>"Jochen", "last_name"=>"Blom", "scopus_author_id"=>"24329317900"}, {"first_name"=>"Thierry", "last_name"=>"Wirth", "scopus_author_id"=>"56256893400"}, {"first_name"=>"Sebastian", "last_name"=>"Jaenicke", "scopus_author_id"=>"35067970900"}, {"first_name"=>"Sieglinde", "last_name"=>"Schuback", "scopus_author_id"=>"54413048400"}, {"first_name"=>"Sabine", "last_name"=>"Rüsch-Gerdes", "scopus_author_id"=>"7005067189"}, {"first_name"=>"Philip", "last_name"=>"Supply", "scopus_author_id"=>"56137080600"}, {"first_name"=>"Jörn", "last_name"=>"Kalinowski", "scopus_author_id"=>"7101959761"}, {"first_name"=>"Stefan", "last_name"=>"Niemann", "scopus_author_id"=>"7006827120"}], "year"=>2013, "source"=>"PLoS Medicine", "identifiers"=>{"pmid"=>"23424287", "doi"=>"10.1371/journal.pmed.1001387", "isbn"=>"1549-1676 (Electronic)\\r1549-1277 (Linking)", "scopus"=>"2-s2.0-84874469388", "issn"=>"15491277", "pui"=>"368439118", "sgr"=>"84874469388"}, "id"=>"c9d4efc7-64c2-3503-a71e-c844d7753633", "abstract"=>"Understanding Mycobacterium tuberculosis (Mtb) transmission is essential to guide efficient tuberculosis control strategies. Traditional strain typing lacks sufficient discriminatory power to resolve large outbreaks. Here, we tested the potential of using next generation genome sequencing for identification of outbreak-related transmission chains.", "link"=>"http://www.mendeley.com/research/whole-genome-sequencing-versus-traditional-genotyping-investigation-mycobacterium-tuberculosis-outbr", "reader_count"=>330, "reader_count_by_academic_status"=>{"Unspecified"=>8, "Professor > Associate Professor"=>10, "Librarian"=>2, "Researcher"=>94, "Student > Doctoral Student"=>15, "Student > Ph. D. Student"=>76, "Student > Postgraduate"=>17, "Student > Master"=>49, "Other"=>9, "Student > Bachelor"=>20, "Lecturer"=>8, "Lecturer > Senior Lecturer"=>3, "Professor"=>19}, "reader_count_by_user_role"=>{"Unspecified"=>8, "Professor > Associate Professor"=>10, "Librarian"=>2, "Researcher"=>94, "Student > Doctoral Student"=>15, "Student > Ph. D. Student"=>76, "Student > Postgraduate"=>17, "Student > Master"=>49, "Other"=>9, "Student > Bachelor"=>20, "Lecturer"=>8, "Lecturer > Senior Lecturer"=>3, "Professor"=>19}, "reader_count_by_subject_area"=>{"Unspecified"=>17, "Agricultural and Biological Sciences"=>154, "Arts and Humanities"=>1, "Veterinary Science and Veterinary Medicine"=>4, "Business, Management and Accounting"=>2, "Chemistry"=>1, "Computer Science"=>5, "Earth and Planetary Sciences"=>1, "Engineering"=>2, "Environmental Science"=>2, "Biochemistry, Genetics and Molecular Biology"=>33, "Nursing and Health Professions"=>3, "Mathematics"=>4, "Medicine and Dentistry"=>77, "Physics and Astronomy"=>1, "Social Sciences"=>7, "Immunology and Microbiology"=>16}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>77}, "Social Sciences"=>{"Social Sciences"=>7}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Mathematics"=>{"Mathematics"=>4}, "Unspecified"=>{"Unspecified"=>17}, "Environmental Science"=>{"Environmental Science"=>2}, "Arts and Humanities"=>{"Arts and Humanities"=>1}, "Engineering"=>{"Engineering"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>16}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>154}, "Computer Science"=>{"Computer Science"=>5}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>2}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>33}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>4}}, "reader_count_by_country"=>{"Colombia"=>2, "United States"=>3, "Sudan"=>1, "United Kingdom"=>5, "Malaysia"=>1, "Thailand"=>1, "India"=>1, "Spain"=>2, "Canada"=>5, "Sweden"=>1, "Belgium"=>2, "Norway"=>1, "Denmark"=>2, "Zimbabwe"=>1, "Mexico"=>1, "Australia"=>1, "Germany"=>2, "Nepal"=>1}, "group_count"=>16}

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/490708"], "description"=>"a<p>Data are given as number (percent) unless otherwise indicated.</p>b<p>The mean ages of the two patient groups were compared using the Wilcoxon rank sum test. All other data were compared using Pearson's χ-squared (or Fisher's exact) test.</p>", "links"=>[], "tags"=>["disease-related", "characteristics", "86", "patients", "studied"], "article_id"=>161213, "categories"=>["Biotechnology", "Infectious Diseases"], "users"=>["Andreas Roetzer", "Roland Diel", "Thomas A. Kohl", "Christian Rückert", "Ulrich Nübel", "Jochen Blom", "Thierry Wirth", "Sebastian Jaenicke", "Sieglinde Schuback", "Sabine Rüsch-Gerdes", "Philip Supply", "Jörn Kalinowski", "Stefan Niemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001387.t001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sociodemographic_and_disease_related_characteristics_of_the_86_patients_in_the_studied_cluster_/161213", "title"=>"Sociodemographic and disease-related characteristics of the 86 patients in the studied cluster.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-12 00:20:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/490393"], "description"=>"<p>Minimum spanning tree allowing hypothetical nodes of the Mtb outbreak in Hamburg and Schleswig-Holstein. The year of isolation is coded by color. HH, Hanseatic City of Hamburg; SH, Schleswig-Holstein. Asterisk indicates the root of the tree determined through comparison with an outgroup (H37Rv).</p>", "links"=>[], "tags"=>["spanning"], "article_id"=>160904, "categories"=>["Biotechnology", "Infectious Diseases"], "users"=>["Andreas Roetzer", "Roland Diel", "Thomas A. Kohl", "Christian Rückert", "Ulrich Nübel", "Jochen Blom", "Thierry Wirth", "Sebastian Jaenicke", "Sieglinde Schuback", "Sabine Rüsch-Gerdes", "Philip Supply", "Jörn Kalinowski", "Stefan Niemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001387.g001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Minimum_spanning_tree_analysis_/160904", "title"=>"Minimum spanning tree analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-12 00:15:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/490762"], "description"=>"a<p>Found to be at least partially deleted in clinical isolates according to Tsolaki et al. <a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001387#pmed.1001387-Tsolaki1\" target=\"_blank\">[38]</a>.</p>", "links"=>[], "tags"=>["regions", "larger", "20", "bp", "mtb", "h37rv", "absent", "aligned"], "article_id"=>161263, "categories"=>["Biotechnology", "Infectious Diseases"], "users"=>["Andreas Roetzer", "Roland Diel", "Thomas A. Kohl", "Christian Rückert", "Ulrich Nübel", "Jochen Blom", "Thierry Wirth", "Sebastian Jaenicke", "Sieglinde Schuback", "Sabine Rüsch-Gerdes", "Philip Supply", "Jörn Kalinowski", "Stefan Niemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001387.t002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genomic_regions_larger_than_20_bp_in_Mtb_H37Rv_that_were_absent_denoted_by_8220_215_8221_in_at_least_one_aligned_strain_/161263", "title"=>"Genomic regions larger than 20 bp in Mtb H37Rv that were absent (denoted by “×”) in at least one aligned strain.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-12 00:21:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/484674", "https://ndownloader.figshare.com/files/484678", "https://ndownloader.figshare.com/files/484679", "https://ndownloader.figshare.com/files/484680", "https://ndownloader.figshare.com/files/484684", "https://ndownloader.figshare.com/files/484687"], "description"=>"<div><h3>Background</h3><p>Understanding <em>Mycobacterium tuberculosis</em> (Mtb) transmission is essential to guide efficient tuberculosis control strategies. Traditional strain typing lacks sufficient discriminatory power to resolve large outbreaks. Here, we tested the potential of using next generation genome sequencing for identification of outbreak-related transmission chains.</p> <h3>Methods and Findings</h3><p>During long-term (1997 to 2010) prospective population-based molecular epidemiological surveillance comprising a total of 2,301 patients, we identified a large outbreak caused by an Mtb strain of the Haarlem lineage. The main performance outcome measure of whole genome sequencing (WGS) analyses was the degree of correlation of the WGS analyses with contact tracing data and the spatio-temporal distribution of the outbreak cases. WGS analyses of the 86 isolates revealed 85 single nucleotide polymorphisms (SNPs), subdividing the outbreak into seven genome clusters (two to 24 isolates each), plus 36 unique SNP profiles. WGS results showed that the first outbreak isolates detected in 1997 were falsely clustered by classical genotyping. In 1998, one clone (termed “<em>Hamburg</em> clone”) started expanding, apparently independently from differences in the social environment of early cases. Genome-based clustering patterns were in better accordance with contact tracing data and the geographical distribution of the cases than clustering patterns based on classical genotyping. A maximum of three SNPs were identified in eight confirmed human-to-human transmission chains, involving 31 patients. We estimated the Mtb genome evolutionary rate at 0.4 mutations per genome per year. This rate suggests that Mtb grows in its natural host with a doubling time of approximately 22 h (400 generations per year). Based on the genome variation discovered, emergence of the <em>Hamburg</em> clone was dated back to a period between 1993 and 1997, hence shortly before the discovery of the outbreak through epidemiological surveillance.</p> <h3>Conclusions</h3><p>Our findings suggest that WGS is superior to conventional genotyping for Mtb pathogen tracing and investigating micro-epidemics. WGS provides a measure of Mtb genome evolution over time in its natural host context.</p> <p> <em>Please see later in the article for the Editors' Summary</em></p> </div>", "links"=>[], "tags"=>["genome", "sequencing", "genotyping", "longitudinal", "molecular", "epidemiological", "study"], "article_id"=>156541, "categories"=>["Biotechnology", "Infectious Diseases"], "users"=>["Andreas Roetzer", "Roland Diel", "Thomas A. Kohl", "Christian Rückert", "Ulrich Nübel", "Jochen Blom", "Thierry Wirth", "Sebastian Jaenicke", "Sieglinde Schuback", "Sabine Rüsch-Gerdes", "Philip Supply", "Jörn Kalinowski", "Stefan Niemann"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1001387.s001", "https://dx.doi.org/10.1371/journal.pmed.1001387.s002", "https://dx.doi.org/10.1371/journal.pmed.1001387.s003", "https://dx.doi.org/10.1371/journal.pmed.1001387.s004", "https://dx.doi.org/10.1371/journal.pmed.1001387.s005", "https://dx.doi.org/10.1371/journal.pmed.1001387.s006"], "stats"=>{"downloads"=>13, "page_views"=>43, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Whole_Genome_Sequencing_versus_Traditional_Genotyping_for_Investigation_of_a_Mycobacterium_tuberculosis_Outbreak_A_Longitudinal_Molecular_Epidemiological_Study__/156541", "title"=>"Whole Genome Sequencing versus Traditional Genotyping for Investigation of a <em>Mycobacterium tuberculosis</em> Outbreak: A Longitudinal Molecular Epidemiological Study", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-02-12 01:49:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/490632"], "description"=>"<p>(A) Members of this outbreak have been continuously isolated over the past 14 y. Isolates of the two distinguishable parts, the “<i>Hamburg</i> clone” and the remaining unsuccessful strains, are shown. Black arrows indicate the first isolations of strains at different sites in Schleswig-Holstein in 2006 (Kiel [K]) and 2010 (Pinneberg [P]). (B) Time course of the Mtb cases and their least-squares regressions. Upper and bottom plots correspond to the Hamburg clone and unsuccessful strains, as shown in (A). Solid and dotted lines represent calculated regression lines and 95% confidence interval boundaries, respectively. Note that both the <i>Hamburg</i> clone and the unrelated strains did not significantly depart from linear growth on this temporal scale, implying that selection coefficients during the epidemic were fairly constant. (C) Explored environmental settings were mapped on the minimum spanning trees shown in <a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001387#pmed-1001387-g001\" target=\"_blank\">Figure 1</a>.</p>", "links"=>[], "tags"=>["mtb", "outbreak", "hamburg"], "article_id"=>161142, "categories"=>["Biotechnology", "Infectious Diseases"], "users"=>["Andreas Roetzer", "Roland Diel", "Thomas A. Kohl", "Christian Rückert", "Ulrich Nübel", "Jochen Blom", "Thierry Wirth", "Sebastian Jaenicke", "Sieglinde Schuback", "Sabine Rüsch-Gerdes", "Philip Supply", "Jörn Kalinowski", "Stefan Niemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001387.g003", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spread_of_the_Mtb_outbreak_in_Hamburg_and_Schleswig_Holstein_/161142", "title"=>"Spread of the Mtb outbreak in Hamburg and Schleswig-Holstein.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-12 00:19:02"}

PMC Usage Stats | Further Information

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Relative Metric

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