Author response: Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area

AbstractIntroductionImproving the surveillance of tuberculosis (TB) is especially important for multidrug-resistant (MDR) and extensively drug-resistant (XDR)-TB. The large amount of publicly available whole-genome sequencing (WGS) data for TB gives us the chance to re-use data and to perform additional analysis at a large scale.AimWe assessed the usefulness of raw WGS data of global MDR/XDR-TB isolates available from public repositories to improve TB surveillance.MethodsWe extracted raw WGS data and the related metadata of Mycobacterium tuberculosis isolates available from the Sequence Read Archive. We compared this public dataset with WGS data and metadata of 131 MDR- and XDR-TB isolates from Germany in 2012-2013.ResultsWe aggregated a dataset that includes 1,081 MDR and 250 XDR isolates among which we identified 133 molecular clusters. In 16 clusters, the isolates were from at least two different countries. For example, cluster2 included 56 MDR/XDR isolates from Moldova, Georgia, and Germany. By comparing the WGS data from Germany and the public dataset, we found that 11 clusters contained at least one isolate from Germany and at least one isolate from another country. We could, therefore, connect TB cases despite missing epidemiological information.ConclusionWe demonstrated the added value of using WGS raw data from public repositories to contribute to TB surveillance. By comparing the German and the public dataset, we identified potential international transmission events. Thus, using this approach might support the interpretation of national surveillance results in an international context.

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Author response for "Whole genome sequencing of consanguineous families reveals novel pathogenic variants in intellectual disability"

10.1111/cge.13470/v2/response1 ◽

2018 ◽

Author(s):

Ann-Charlotte Thuresson ◽

Cecilia Soussi Zander ◽

Jin J. Zhao ◽

Jonatan Halvardson ◽

Khurram Maqbool ◽

...

Keyword(s):

Intellectual Disability ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Author Response ◽

Whole Genome ◽

Pathogenic Variants

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Whole genome sequencing identifies bacterial factors affecting transmission of multidrug-resistant tuberculosis in a high-prevalence setting

Scientific Reports ◽

10.1038/s41598-019-41967-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 7

Author(s):

Avika Dixit ◽

Luca Freschi ◽

Roger Vargas ◽

Roger Calderon ◽

James Sacchettini ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Multidrug Resistant ◽

Whole Genome ◽

Factors Affecting ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

High Prevalence

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Recombinational Switching of the Clostridium difficile S-Layer and a Novel Glycosylation Gene Cluster Revealed by Large-Scale Whole-Genome Sequencing

The Journal of Infectious Diseases ◽

10.1093/infdis/jis734 ◽

2012 ◽

Vol 207 (4) ◽

pp. 675-686 ◽

Cited By ~ 58

Author(s):

Kate E. Dingle ◽

Xavier Didelot ◽

M. Azim Ansari ◽

David W. Eyre ◽

Alison Vaughan ◽

...

Keyword(s):

Clostridium Difficile ◽

Whole Genome Sequencing ◽

Gene Cluster ◽

Genome Sequencing ◽

Large Scale ◽

Whole Genome

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Whole-Genome Sequencing for Routine Pathogen Surveillance in Public Health: a Population Snapshot of InvasiveStaphylococcus aureusin Europe

mBio ◽

10.1128/mbio.00444-16 ◽

2016 ◽

Vol 7 (3) ◽

Cited By ~ 123

Author(s):

David M. Aanensen ◽

Edward J. Feil ◽

Matthew T. G. Holden ◽

Janina Dordel ◽

Corin A. Yeats ◽

...

Keyword(s):

Public Health ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Large Scale ◽

Bacterial Pathogens ◽

Epidemiological Surveillance ◽

Data Sets ◽

Whole Genome ◽

Bioinformatic Tools ◽

Road Map

ABSTRACTThe implementation of routine whole-genome sequencing (WGS) promises to transform our ability to monitor the emergence and spread of bacterial pathogens. Here we combined WGS data from 308 invasiveStaphylococcus aureusisolates corresponding to a pan-European population snapshot, with epidemiological and resistance data. Geospatial visualization of the data is made possible by a generic software tool designed for public health purposes that is available at the project URL (http://www.microreact.org/project/EkUvg9uY?tt=rc). Our analysis demonstrates that high-risk clones can be identified on the basis of population level properties such as clonal relatedness, abundance, and spatial structuring and by inferring virulence and resistance properties on the basis of gene content. We also show thatin silicopredictions of antibiotic resistance profiles are at least as reliable as phenotypic testing. We argue that this work provides a comprehensive road map illustrating the three vital components for future molecular epidemiological surveillance: (i) large-scale structured surveys, (ii) WGS, and (iii) community-oriented database infrastructure and analysis tools.IMPORTANCEThe spread of antibiotic-resistant bacteria is a public health emergency of global concern, threatening medical intervention at every level of health care delivery. Several recent studies have demonstrated the promise of routine whole-genome sequencing (WGS) of bacterial pathogens for epidemiological surveillance, outbreak detection, and infection control. However, as this technology becomes more widely adopted, the key challenges of generating representative national and international data sets and the development of bioinformatic tools to manage and interpret the data become increasingly pertinent. This study provides a road map for the integration of WGS data into routine pathogen surveillance. We emphasize the importance of large-scale routine surveys to provide the population context for more targeted or localized investigation and the development of open-access bioinformatic tools to provide the means to combine and compare independently generated data with publicly available data sets.

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