Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates

dc.contributor.authorHeunis, Tiaan
dc.contributor.authorDippenaar, Anzaan
dc.contributor.authorWarren, Robin M.
dc.contributor.authorvan Helden, Paul D.
dc.contributor.authorvan der Merwe, Ruben G.
dc.contributor.authorGey van Pittius, Nicolaas C.
dc.contributor.authorPain, Arnab
dc.contributor.authorSampson, Samantha L.
dc.contributor.authorTabb, David L.
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.contributor.departmentPathogen Genomics Laboratory
dc.contributor.institutionDST/NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
dc.date.accessioned2017-08-23T11:54:06Z
dc.date.available2017-08-23T11:54:06Z
dc.date.issued2017-09-11
dc.date.published-online2017-09-11
dc.date.published-print2017-10-06
dc.description.abstractMycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study we integrated whole-genome sequencing and mass spectrometry (GeLC-MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M. tuberculosis Latin American-Mediterranean isolates. Using this approach we identified 59 peptides containing single amino acid variants, which covered ~9% of all total coding nonsynonymous single nucleotide variants detected by whole-genome sequencing. Furthermore, we identified 29 distinct peptides that mapped to a hypothetical protein not present in the M. tuberculosis H37Rv reference proteome. Here we provide evidence for the expression of this protein in the clinical M. tuberculosis SAWC3651 isolate. The strain-specific databases enabled confirmation of genomic differences (i.e. large genomic regions of difference and nonsynonymous single nucleotide variants) in these two clinical M. tuberculosis isolates and allowed strain differentiation at the proteome level. Our results contribute to the growing field of clinical microbial proteogenomics and can improve our understanding of phenotypic variation in clinical M. tuberculosis isolates.
dc.description.sponsorshipThis work was supported by the South African National Research Foundation (NRF), South African Medical Research Council (SAMRC), Harry Crossley Foundation, Claude Leon Foundation, the Department of Biomedical Sciences, Stellenbosch University and King Abdullah University of Science and Technology (KAUST award number BAS/1/1020-01-01). S.L. Sampson is funded by the South African Research Chairs Initiative of the Department of Science and Technology and NRF of South Africa, award number UID 86539. D.L. Tabb is funded by the SAMRC under the South African Tuberculosis Bioinformatics Initiative.
dc.eprint.versionPost-print
dc.identifier.citationHeunis T, Dippenaar A, Warren RM, van Helden PD, van der Merwe RG, et al. (2017) Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates. Journal of Proteome Research. Available: http://dx.doi.org/10.1021/acs.jproteome.7b00483.
dc.identifier.doi10.1021/acs.jproteome.7b00483
dc.identifier.issn1535-3893
dc.identifier.issn1535-3907
dc.identifier.journalJournal of Proteome Research
dc.identifier.urihttp://hdl.handle.net/10754/625389
dc.internal.reviewer-noteEmbargo until (dd/mm/yyyy): 18/08/2018
dc.publisherAmerican Chemical Society (ACS)
dc.relation.urlhttp://pubs.acs.org/doi/abs/10.1021/acs.jproteome.7b00483
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Proteome Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.jproteome.7b00483.
dc.subjectMycobacterium tuberculosis
dc.subjectclinical microbial proteogenomics
dc.subjectvariant peptides
dc.subjectstrain variation
dc.titleProteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates
dc.typeArticle
display.details.left<span><h5>Type</h5>Article<br><br><h5>Authors</h5><a href="https://repository.kaust.edu.sa/search?spc.sf=dc.date.issued&spc.sd=DESC&f.author=Heunis, Tiaan,equals">Heunis, Tiaan</a><br><a href="https://repository.kaust.edu.sa/search?spc.sf=dc.date.issued&spc.sd=DESC&f.author=Dippenaar, Anzaan,equals">Dippenaar, Anzaan</a><br><a href="https://repository.kaust.edu.sa/search?spc.sf=dc.date.issued&spc.sd=DESC&f.author=Warren, Robin M.,equals">Warren, Robin M.</a><br><a href="https://repository.kaust.edu.sa/search?spc.sf=dc.date.issued&spc.sd=DESC&f.author=van Helden, Paul D.,equals">van Helden, Paul D.</a><br><a href="https://repository.kaust.edu.sa/search?spc.sf=dc.date.issued&spc.sd=DESC&f.author=van der Merwe, Ruben G.,equals">van der Merwe, Ruben G.</a><br><a href="https://repository.kaust.edu.sa/search?spc.sf=dc.date.issued&spc.sd=DESC&f.author=Gey van Pittius, Nicolaas C.,equals">Gey van Pittius, Nicolaas C.</a><br><a href="https://repository.kaust.edu.sa/search?query=orcid.id:0000-0002-1755-2819&spc.sf=dc.date.issued&spc.sd=DESC">Pain, Arnab</a> <a href="https://orcid.org/0000-0002-1755-2819" target="_blank"><img src="https://repository.kaust.edu.sa/server/api/core/bitstreams/82a625b4-ed4b-40c8-865a-d6a5225a26a4/content" width="16" height="16"/></a><br><a href="https://repository.kaust.edu.sa/search?spc.sf=dc.date.issued&spc.sd=DESC&f.author=Sampson, Samantha L.,equals">Sampson, Samantha L.</a><br><a href="https://repository.kaust.edu.sa/search?spc.sf=dc.date.issued&spc.sd=DESC&f.author=Tabb, David L.,equals">Tabb, David L.</a><br><br><h5>KAUST Department</h5><a href="https://repository.kaust.edu.sa/search?spc.sf=dc.date.issued&spc.sd=DESC&f.department=Biological and Environmental Sciences and Engineering (BESE) Division,equals">Biological and Environmental Sciences and Engineering (BESE) Division</a><br><a href="https://repository.kaust.edu.sa/search?spc.sf=dc.date.issued&spc.sd=DESC&f.department=Bioscience Program,equals">Bioscience Program</a><br><a href="https://repository.kaust.edu.sa/search?spc.sf=dc.date.issued&spc.sd=DESC&f.department=Pathogen Genomics Laboratory,equals">Pathogen Genomics Laboratory</a><br><br><h5>Online Publication Date</h5>2017-09-11<br><br><h5>Print Publication Date</h5>2017-10-06<br><br><h5>Date</h5>2017-09-11</span>
display.details.right<span><h5>Abstract</h5>Mycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study we integrated whole-genome sequencing and mass spectrometry (GeLC-MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M. tuberculosis Latin American-Mediterranean isolates. Using this approach we identified 59 peptides containing single amino acid variants, which covered ~9% of all total coding nonsynonymous single nucleotide variants detected by whole-genome sequencing. Furthermore, we identified 29 distinct peptides that mapped to a hypothetical protein not present in the M. tuberculosis H37Rv reference proteome. Here we provide evidence for the expression of this protein in the clinical M. tuberculosis SAWC3651 isolate. The strain-specific databases enabled confirmation of genomic differences (i.e. large genomic regions of difference and nonsynonymous single nucleotide variants) in these two clinical M. tuberculosis isolates and allowed strain differentiation at the proteome level. Our results contribute to the growing field of clinical microbial proteogenomics and can improve our understanding of phenotypic variation in clinical M. tuberculosis isolates.<br><br><h5>Citation</h5>Heunis T, Dippenaar A, Warren RM, van Helden PD, van der Merwe RG, et al. (2017) Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates. Journal of Proteome Research. Available: http://dx.doi.org/10.1021/acs.jproteome.7b00483.<br><br><h5>Acknowledgements</h5>This work was supported by the South African National Research Foundation (NRF), South African Medical Research Council (SAMRC), Harry Crossley Foundation, Claude Leon Foundation, the Department of Biomedical Sciences, Stellenbosch University and King Abdullah University of Science and Technology (KAUST award number BAS/1/1020-01-01). S.L. Sampson is funded by the South African Research Chairs Initiative of the Department of Science and Technology and NRF of South Africa, award number UID 86539. D.L. Tabb is funded by the SAMRC under the South African Tuberculosis Bioinformatics Initiative.<br><br><h5>Publisher</h5><a href="https://repository.kaust.edu.sa/search?spc.sf=dc.date.issued&spc.sd=DESC&f.publisher=American Chemical Society (ACS),equals">American Chemical Society (ACS)</a><br><br><h5>Journal</h5><a href="https://repository.kaust.edu.sa/search?spc.sf=dc.date.issued&spc.sd=DESC&f.journal=Journal of Proteome Research,equals">Journal of Proteome Research</a><br><br><h5>DOI</h5><a href="https://doi.org/10.1021/acs.jproteome.7b00483">10.1021/acs.jproteome.7b00483</a><br><br><h5>Additional Links</h5>http://pubs.acs.org/doi/abs/10.1021/acs.jproteome.7b00483</span>
kaust.personPain, Arnab
orcid.authorHeunis, Tiaan
orcid.authorDippenaar, Anzaan
orcid.authorWarren, Robin M.
orcid.authorvan Helden, Paul D.
orcid.authorvan der Merwe, Ruben G.
orcid.authorGey van Pittius, Nicolaas C.
orcid.authorPain, Arnab::0000-0002-1755-2819
orcid.authorSampson, Samantha L.
orcid.authorTabb, David L.
orcid.id0000-0002-1755-2819
refterms.dateFOA2018-08-18T00:00:00Z
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