Comparative whole-genome analysis of clinical isolates reveals characteristic architecture of Mycobacterium tuberculosis pangenome
The tubercle complex consists of closely related mycobacterium species which appear to be variants of a single species. Comparative genome analysis of different strains could provide useful clues and insights into the genetic diversity of the species. We integrated genome assemblies of 96 strains fr...
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| creator | Periwal, Vinita Patowary, Ashok Vellarikkal, Shamsudheen Karuthedath Gupta, Anju Singh, Meghna Mittal, Ashish Jeyapaul, Shamini Chauhan, Rajendra Kumar Singh, Ajay Vir Singh, Pravin Kumar Garg, Parul Katoch, Viswa Mohan Katoch, Kiran Chauhan, Devendra Singh Sivasubbu, Sridhar Scaria, Vinod |
| description | The tubercle complex consists of closely related mycobacterium species which appear to be variants of a single species. Comparative genome analysis of different strains could provide useful clues and insights into the genetic diversity of the species. We integrated genome assemblies of 96 strains from Mycobacterium tuberculosis complex (MTBC), which included 8 Indian clinical isolates sequenced and assembled in this study, to understand its pangenome architecture. We predicted genes for all the 96 strains and clustered their respective CDSs into homologous gene clusters (HGCs) to reveal a hard-core, soft-core and accessory genome component of MTBC. The hard-core (HGCs shared amongst 100% of the strains) was comprised of 2,066 gene clusters whereas the soft-core (HGCs shared amongst at least 95% of the strains) comprised of 3,374 gene clusters. The change in the core and accessory genome components when observed as a function of their size revealed that MTBC has an open pangenome. We identified 74 HGCs that were absent from reference strains H37Rv and H37Ra but were present in most of clinical isolates. We report PCR validation on 9 candidate genes depicting 7 genes completely absent from H37Rv and H37Ra whereas 2 genes shared partial homology with them accounting to probable insertion and deletion events. The pangenome approach is a promising tool for studying strain specific genetic differences occurring within species. We also suggest that since selecting appropriate target genes for typing purposes requires the expected target gene be present in all isolates being typed, therefore estimating the core-component of the species becomes a subject of prime importance. |
| doi_str_mv | 10.1371/journal.pone.0122979 |
| format | Article |
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Comparative genome analysis of different strains could provide useful clues and insights into the genetic diversity of the species. We integrated genome assemblies of 96 strains from Mycobacterium tuberculosis complex (MTBC), which included 8 Indian clinical isolates sequenced and assembled in this study, to understand its pangenome architecture. We predicted genes for all the 96 strains and clustered their respective CDSs into homologous gene clusters (HGCs) to reveal a hard-core, soft-core and accessory genome component of MTBC. The hard-core (HGCs shared amongst 100% of the strains) was comprised of 2,066 gene clusters whereas the soft-core (HGCs shared amongst at least 95% of the strains) comprised of 3,374 gene clusters. The change in the core and accessory genome components when observed as a function of their size revealed that MTBC has an open pangenome. We identified 74 HGCs that were absent from reference strains H37Rv and H37Ra but were present in most of clinical isolates. We report PCR validation on 9 candidate genes depicting 7 genes completely absent from H37Rv and H37Ra whereas 2 genes shared partial homology with them accounting to probable insertion and deletion events. The pangenome approach is a promising tool for studying strain specific genetic differences occurring within species. We also suggest that since selecting appropriate target genes for typing purposes requires the expected target gene be present in all isolates being typed, therefore estimating the core-component of the species becomes a subject of prime importance.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0122979</identifier><identifier>PMID: 25853708</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Algorithms ; Architecture ; Base Sequence ; Biodiversity ; Bioinformatics ; Biology ; Care and treatment ; Clinical isolates ; Clusters ; Comparative Genomic Hybridization ; Complications and side effects ; DNA, Bacterial - genetics ; Drug resistance ; E coli ; Escherichia coli ; Gene clusters ; Genes ; Genetic diversity ; Genetic Variation ; Genome, Bacterial ; Genome-wide association studies ; Genomes ; Genomics ; Gram-positive bacteria ; Homology ; Humans ; Infections ; Informatics ; Insertion ; Laboratories ; Leprosy ; Medicine ; Morbidity ; Multilocus sequence typing ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - classification ; Mycobacterium tuberculosis - genetics ; Mycobacterium tuberculosis - pathogenicity ; Phylogeny ; Risk factors ; Species ; Species diversity ; Tuberculosis ; Tuberculosis - genetics ; Tuberculosis - microbiology ; Tuberculosis - pathology</subject><ispartof>PloS one, 2015-04, Vol.10 (4), p.e0122979-e0122979</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Periwal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Periwal et al 2015 Periwal et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c651t-4517ae0f1f303ad75b014a671907695483279be2bc4eb339d584cb01c5d96df33</citedby><cites>FETCH-LOGICAL-c651t-4517ae0f1f303ad75b014a671907695483279be2bc4eb339d584cb01c5d96df33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390332/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390332/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25853708$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Periwal, Vinita</creatorcontrib><creatorcontrib>Patowary, Ashok</creatorcontrib><creatorcontrib>Vellarikkal, Shamsudheen Karuthedath</creatorcontrib><creatorcontrib>Gupta, Anju</creatorcontrib><creatorcontrib>Singh, Meghna</creatorcontrib><creatorcontrib>Mittal, Ashish</creatorcontrib><creatorcontrib>Jeyapaul, Shamini</creatorcontrib><creatorcontrib>Chauhan, Rajendra Kumar</creatorcontrib><creatorcontrib>Singh, Ajay Vir</creatorcontrib><creatorcontrib>Singh, Pravin Kumar</creatorcontrib><creatorcontrib>Garg, Parul</creatorcontrib><creatorcontrib>Katoch, Viswa Mohan</creatorcontrib><creatorcontrib>Katoch, Kiran</creatorcontrib><creatorcontrib>Chauhan, Devendra Singh</creatorcontrib><creatorcontrib>Sivasubbu, Sridhar</creatorcontrib><creatorcontrib>Scaria, Vinod</creatorcontrib><title>Comparative whole-genome analysis of clinical isolates reveals characteristic architecture of Mycobacterium tuberculosis pangenome</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The tubercle complex consists of closely related mycobacterium species which appear to be variants of a single species. Comparative genome analysis of different strains could provide useful clues and insights into the genetic diversity of the species. We integrated genome assemblies of 96 strains from Mycobacterium tuberculosis complex (MTBC), which included 8 Indian clinical isolates sequenced and assembled in this study, to understand its pangenome architecture. We predicted genes for all the 96 strains and clustered their respective CDSs into homologous gene clusters (HGCs) to reveal a hard-core, soft-core and accessory genome component of MTBC. The hard-core (HGCs shared amongst 100% of the strains) was comprised of 2,066 gene clusters whereas the soft-core (HGCs shared amongst at least 95% of the strains) comprised of 3,374 gene clusters. The change in the core and accessory genome components when observed as a function of their size revealed that MTBC has an open pangenome. We identified 74 HGCs that were absent from reference strains H37Rv and H37Ra but were present in most of clinical isolates. We report PCR validation on 9 candidate genes depicting 7 genes completely absent from H37Rv and H37Ra whereas 2 genes shared partial homology with them accounting to probable insertion and deletion events. The pangenome approach is a promising tool for studying strain specific genetic differences occurring within species. We also suggest that since selecting appropriate target genes for typing purposes requires the expected target gene be present in all isolates being typed, therefore estimating the core-component of the species becomes a subject of prime importance.</description><subject>Acids</subject><subject>Algorithms</subject><subject>Architecture</subject><subject>Base Sequence</subject><subject>Biodiversity</subject><subject>Bioinformatics</subject><subject>Biology</subject><subject>Care and treatment</subject><subject>Clinical isolates</subject><subject>Clusters</subject><subject>Comparative Genomic Hybridization</subject><subject>Complications and side effects</subject><subject>DNA, Bacterial - genetics</subject><subject>Drug resistance</subject><subject>E coli</subject><subject>Escherichia coli</subject><subject>Gene clusters</subject><subject>Genes</subject><subject>Genetic diversity</subject><subject>Genetic Variation</subject><subject>Genome, Bacterial</subject><subject>Genome-wide association studies</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Gram-positive bacteria</subject><subject>Homology</subject><subject>Humans</subject><subject>Infections</subject><subject>Informatics</subject><subject>Insertion</subject><subject>Laboratories</subject><subject>Leprosy</subject><subject>Medicine</subject><subject>Morbidity</subject><subject>Multilocus sequence typing</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - classification</subject><subject>Mycobacterium tuberculosis - genetics</subject><subject>Mycobacterium tuberculosis - pathogenicity</subject><subject>Phylogeny</subject><subject>Risk factors</subject><subject>Species</subject><subject>Species diversity</subject><subject>Tuberculosis</subject><subject>Tuberculosis - genetics</subject><subject>Tuberculosis - microbiology</subject><subject>Tuberculosis - pathology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptkk1v1DAQhiMEoqXwDxBEQkJcdvFX7PhSqVrxUamIC5wtx5lsvErixXYW7ZVfjtOk1S7iZMvzzjPzjifLXmO0xlTgjzs3-kF3670bYI0wIVLIJ9kllpSsOEH06cn9InsRwg6hgpacP88uSFEWVKDyMvuzcf1eex3tAfLfretgtYXB9ZDrBD8GG3LX5KazgzW6y21wnY4Qcg8H0F3ITZuSTQRvQ7Qm1960NoKJo4cp8dvRuGqOj30exwq8GTs3Yfd6mCu9zJ41CQWvlvMq-_n504_N19Xd9y-3m5u7leEFjitWYKEBNbihiOpaFBXCTHOBJRJcFqykRMgKSGUYVJTKuiiZSRpT1JLXDaVX2duZu08NqGV8QeGEIJhzwZPidlbUTu_U3tte-6Ny2qr7B-e3SvtkswPFMRKNKKHGApjkQnOuEcJYNkwSaUhiXS_VxqqH2sAQve7OoOeRwbZq6w6KUYkonQAfFoB3v0YIUfU2GOg6PYAb7_smHImSTc7e_SP9v7tFtdXJgB0al-qaCapuGJFUMEZFUr0_UbXpk2ObPn2M1g3hXMhmofEuBA_NozeM1LShD02oaUPVsqEp7c3pXB6THlaS_gUnZOUO</recordid><startdate>20150408</startdate><enddate>20150408</enddate><creator>Periwal, Vinita</creator><creator>Patowary, Ashok</creator><creator>Vellarikkal, Shamsudheen Karuthedath</creator><creator>Gupta, Anju</creator><creator>Singh, Meghna</creator><creator>Mittal, Ashish</creator><creator>Jeyapaul, Shamini</creator><creator>Chauhan, Rajendra Kumar</creator><creator>Singh, Ajay Vir</creator><creator>Singh, Pravin Kumar</creator><creator>Garg, Parul</creator><creator>Katoch, Viswa Mohan</creator><creator>Katoch, Kiran</creator><creator>Chauhan, Devendra Singh</creator><creator>Sivasubbu, Sridhar</creator><creator>Scaria, Vinod</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150408</creationdate><title>Comparative whole-genome analysis of clinical isolates reveals characteristic architecture of Mycobacterium tuberculosis pangenome</title><author>Periwal, Vinita ; Patowary, Ashok ; Vellarikkal, Shamsudheen Karuthedath ; Gupta, Anju ; Singh, Meghna ; Mittal, Ashish ; Jeyapaul, Shamini ; Chauhan, Rajendra Kumar ; Singh, Ajay Vir ; Singh, Pravin Kumar ; Garg, Parul ; Katoch, Viswa Mohan ; Katoch, Kiran ; Chauhan, Devendra Singh ; Sivasubbu, Sridhar ; Scaria, Vinod</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c651t-4517ae0f1f303ad75b014a671907695483279be2bc4eb339d584cb01c5d96df33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Acids</topic><topic>Algorithms</topic><topic>Architecture</topic><topic>Base Sequence</topic><topic>Biodiversity</topic><topic>Bioinformatics</topic><topic>Biology</topic><topic>Care and treatment</topic><topic>Clinical isolates</topic><topic>Clusters</topic><topic>Comparative Genomic Hybridization</topic><topic>Complications and side effects</topic><topic>DNA, Bacterial - 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Comparative genome analysis of different strains could provide useful clues and insights into the genetic diversity of the species. We integrated genome assemblies of 96 strains from Mycobacterium tuberculosis complex (MTBC), which included 8 Indian clinical isolates sequenced and assembled in this study, to understand its pangenome architecture. We predicted genes for all the 96 strains and clustered their respective CDSs into homologous gene clusters (HGCs) to reveal a hard-core, soft-core and accessory genome component of MTBC. The hard-core (HGCs shared amongst 100% of the strains) was comprised of 2,066 gene clusters whereas the soft-core (HGCs shared amongst at least 95% of the strains) comprised of 3,374 gene clusters. The change in the core and accessory genome components when observed as a function of their size revealed that MTBC has an open pangenome. We identified 74 HGCs that were absent from reference strains H37Rv and H37Ra but were present in most of clinical isolates. We report PCR validation on 9 candidate genes depicting 7 genes completely absent from H37Rv and H37Ra whereas 2 genes shared partial homology with them accounting to probable insertion and deletion events. The pangenome approach is a promising tool for studying strain specific genetic differences occurring within species. We also suggest that since selecting appropriate target genes for typing purposes requires the expected target gene be present in all isolates being typed, therefore estimating the core-component of the species becomes a subject of prime importance.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25853708</pmid><doi>10.1371/journal.pone.0122979</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-04, Vol.10 (4), p.e0122979-e0122979 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1671216676 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acids Algorithms Architecture Base Sequence Biodiversity Bioinformatics Biology Care and treatment Clinical isolates Clusters Comparative Genomic Hybridization Complications and side effects DNA, Bacterial - genetics Drug resistance E coli Escherichia coli Gene clusters Genes Genetic diversity Genetic Variation Genome, Bacterial Genome-wide association studies Genomes Genomics Gram-positive bacteria Homology Humans Infections Informatics Insertion Laboratories Leprosy Medicine Morbidity Multilocus sequence typing Mycobacterium tuberculosis Mycobacterium tuberculosis - classification Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - pathogenicity Phylogeny Risk factors Species Species diversity Tuberculosis Tuberculosis - genetics Tuberculosis - microbiology Tuberculosis - pathology |
| title | Comparative whole-genome analysis of clinical isolates reveals characteristic architecture of Mycobacterium tuberculosis pangenome |
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