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Use of Whole Genome Sequencing in Understanding Transmission Dynamics of Tuberculosis / Rhys C. Jones

DOI (Published version): 10.23889/Suthesis.44995

Abstract

Mycobacterium tuberculosis is the leading cause of death from an infectious disease worldwide. An understanding of tuberculosis transmission dynamics in outbreak settings is vital for its control. The advent of affordable whole genome sequencing (WGS) has provided scope for superior resolution of tu...

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Published: 2018
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa44995
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fullrecord <?xml version="1.0"?><rfc1807><datestamp>2018-10-19T10:16:17.5915331</datestamp><bib-version>v2</bib-version><id>44995</id><entry>2018-10-18</entry><title>Use of Whole Genome Sequencing in Understanding Transmission Dynamics of Tuberculosis</title><swanseaauthors/><date>2018-10-18</date><abstract>Mycobacterium tuberculosis is the leading cause of death from an infectious disease worldwide. An understanding of tuberculosis transmission dynamics in outbreak settings is vital for its control. The advent of affordable whole genome sequencing (WGS) has provided scope for superior resolution of tuberculosis outbreaks, compared to previous methods. However, the challenge lies in standardising the vast quantities of resulting data in a structured manner which lends itself to easy comparison of isolates. Gene-by-gene Multi-Locus Sequence Typing (MLST) methods of analysing WGS data, as opposed to Single Nucleotide Polymorphism (SNP) mapping, have shown promise in providing a uniform platform for outbreak resolution.WGS was performed on clinical isolates from three M. tuberculosis outbreaks in South West Wales. Molecular typing by MIRU-VNTR and epidemiological investigation had resulted in conflicting conclusions. Outbreak analysis and phylogenetic typing of all isolates was carried out using the WGS gene-by-gene MLST analysis method of core genome MLST (cgMLST) and traditional WGS SNP mapping. Where DNA quality was unsatisfactory, an ancient DNA library preparation was used successfully. Provean and BEAST software analysis provided physiological information and ancestral dating respectively on outbreak isolates. WGS successfully resolved all three outbreaks, with cgMLST providing clear conclusions across each outbreak. Traditional SNP mapping provided greater resolution than cgMLST in one outbreak. Ancestral dating also proved useful in understanding the outbreaks.Phylogenetically, the dataset was dominated by Euro-American lineage strains, providing the first snapshot of tuberculosis diversity within Wales. Provean analysis identified physiological features in isolates worthy of future research.In summary, WGS was successfully used to resolve three M. tuberculosis outbreaks across South West Wales and correlated better with the epidemiological data than molecular typing by MIRU-VNTR had done. The study highlighted the dominance of the Euro-American lineage within the outbreaks and included the first use of ancient DNA library preparation in a clinical outbreak.</abstract><type>E-Thesis</type><journal/><publisher/><keywords>WGS, Tuberculosis, Epidemiology, DNA, Transmission</keywords><publishedDay>31</publishedDay><publishedMonth>12</publishedMonth><publishedYear>2018</publishedYear><publishedDate>2018-12-31</publishedDate><doi>10.23889/Suthesis.44995</doi><url/><notes>A selection of third party content is redacted or is partially redacted from this thesis.</notes><college>COLLEGE NANME</college><CollegeCode>COLLEGE CODE</CollegeCode><institution>Swansea University</institution><degreelevel>Doctoral</degreelevel><degreename>Ph.D</degreename><apcterm/><lastEdited>2018-10-19T10:16:17.5915331</lastEdited><Created>2018-10-18T12:00:58.1378122</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>Rhys C.</firstname><surname>Jones</surname><order>1</order></author></authors><documents><document><filename>0044995-19102018101143.pdf</filename><originalFilename>Jones_Rhys_C_Final_PhD_Thesis_Redacted.pdf</originalFilename><uploaded>2018-10-19T10:11:43.1570000</uploaded><type>Output</type><contentLength>3608759</contentLength><contentType>application/pdf</contentType><version>Redacted version - open access</version><cronfaStatus>true</cronfaStatus><embargoDate>2018-10-18T00:00:00.0000000</embargoDate><copyrightCorrect>true</copyrightCorrect></document></documents><OutputDurs/></rfc1807>
spelling 2018-10-19T10:16:17.5915331 v2 44995 2018-10-18 Use of Whole Genome Sequencing in Understanding Transmission Dynamics of Tuberculosis 2018-10-18 Mycobacterium tuberculosis is the leading cause of death from an infectious disease worldwide. An understanding of tuberculosis transmission dynamics in outbreak settings is vital for its control. The advent of affordable whole genome sequencing (WGS) has provided scope for superior resolution of tuberculosis outbreaks, compared to previous methods. However, the challenge lies in standardising the vast quantities of resulting data in a structured manner which lends itself to easy comparison of isolates. Gene-by-gene Multi-Locus Sequence Typing (MLST) methods of analysing WGS data, as opposed to Single Nucleotide Polymorphism (SNP) mapping, have shown promise in providing a uniform platform for outbreak resolution.WGS was performed on clinical isolates from three M. tuberculosis outbreaks in South West Wales. Molecular typing by MIRU-VNTR and epidemiological investigation had resulted in conflicting conclusions. Outbreak analysis and phylogenetic typing of all isolates was carried out using the WGS gene-by-gene MLST analysis method of core genome MLST (cgMLST) and traditional WGS SNP mapping. Where DNA quality was unsatisfactory, an ancient DNA library preparation was used successfully. Provean and BEAST software analysis provided physiological information and ancestral dating respectively on outbreak isolates. WGS successfully resolved all three outbreaks, with cgMLST providing clear conclusions across each outbreak. Traditional SNP mapping provided greater resolution than cgMLST in one outbreak. Ancestral dating also proved useful in understanding the outbreaks.Phylogenetically, the dataset was dominated by Euro-American lineage strains, providing the first snapshot of tuberculosis diversity within Wales. Provean analysis identified physiological features in isolates worthy of future research.In summary, WGS was successfully used to resolve three M. tuberculosis outbreaks across South West Wales and correlated better with the epidemiological data than molecular typing by MIRU-VNTR had done. The study highlighted the dominance of the Euro-American lineage within the outbreaks and included the first use of ancient DNA library preparation in a clinical outbreak. E-Thesis WGS, Tuberculosis, Epidemiology, DNA, Transmission 31 12 2018 2018-12-31 10.23889/Suthesis.44995 A selection of third party content is redacted or is partially redacted from this thesis. COLLEGE NANME COLLEGE CODE Swansea University Doctoral Ph.D 2018-10-19T10:16:17.5915331 2018-10-18T12:00:58.1378122 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Rhys C. Jones 1 0044995-19102018101143.pdf Jones_Rhys_C_Final_PhD_Thesis_Redacted.pdf 2018-10-19T10:11:43.1570000 Output 3608759 application/pdf Redacted version - open access true 2018-10-18T00:00:00.0000000 true
title Use of Whole Genome Sequencing in Understanding Transmission Dynamics of Tuberculosis
spellingShingle Use of Whole Genome Sequencing in Understanding Transmission Dynamics of Tuberculosis
,
title_short Use of Whole Genome Sequencing in Understanding Transmission Dynamics of Tuberculosis
title_full Use of Whole Genome Sequencing in Understanding Transmission Dynamics of Tuberculosis
title_fullStr Use of Whole Genome Sequencing in Understanding Transmission Dynamics of Tuberculosis
title_full_unstemmed Use of Whole Genome Sequencing in Understanding Transmission Dynamics of Tuberculosis
title_sort Use of Whole Genome Sequencing in Understanding Transmission Dynamics of Tuberculosis
author ,
author2 Rhys C. Jones
format E-Thesis
publishDate 2018
institution Swansea University
doi_str_mv 10.23889/Suthesis.44995
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description Mycobacterium tuberculosis is the leading cause of death from an infectious disease worldwide. An understanding of tuberculosis transmission dynamics in outbreak settings is vital for its control. The advent of affordable whole genome sequencing (WGS) has provided scope for superior resolution of tuberculosis outbreaks, compared to previous methods. However, the challenge lies in standardising the vast quantities of resulting data in a structured manner which lends itself to easy comparison of isolates. Gene-by-gene Multi-Locus Sequence Typing (MLST) methods of analysing WGS data, as opposed to Single Nucleotide Polymorphism (SNP) mapping, have shown promise in providing a uniform platform for outbreak resolution.WGS was performed on clinical isolates from three M. tuberculosis outbreaks in South West Wales. Molecular typing by MIRU-VNTR and epidemiological investigation had resulted in conflicting conclusions. Outbreak analysis and phylogenetic typing of all isolates was carried out using the WGS gene-by-gene MLST analysis method of core genome MLST (cgMLST) and traditional WGS SNP mapping. Where DNA quality was unsatisfactory, an ancient DNA library preparation was used successfully. Provean and BEAST software analysis provided physiological information and ancestral dating respectively on outbreak isolates. WGS successfully resolved all three outbreaks, with cgMLST providing clear conclusions across each outbreak. Traditional SNP mapping provided greater resolution than cgMLST in one outbreak. Ancestral dating also proved useful in understanding the outbreaks.Phylogenetically, the dataset was dominated by Euro-American lineage strains, providing the first snapshot of tuberculosis diversity within Wales. Provean analysis identified physiological features in isolates worthy of future research.In summary, WGS was successfully used to resolve three M. tuberculosis outbreaks across South West Wales and correlated better with the epidemiological data than molecular typing by MIRU-VNTR had done. The study highlighted the dominance of the Euro-American lineage within the outbreaks and included the first use of ancient DNA library preparation in a clinical outbreak.
published_date 2018-12-31T03:56:32Z
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score 11.03559

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