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Studies mapping genomic heterogeneity in clinical isolates of\n                    <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                    using a whole-genome sequencing approach from high tuberculosis burden countries are underrepresented. We report whole-genome sequencing results of 242 clinical isolates of culture-confirmed\n                    <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                    isolates from tuberculosis patients referred to a tertiary care hospital in Southern India. Phylogenetic analysis revealed that the isolates in our study belonged to five different lineages, with Indo-Oceanic (lineage 1,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 122) and East-African Indian (lineage 3,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 80) being the most prevalent. We report several mutations in genes conferring resistance to first and second line antitubercular drugs including the genes\n                    <jats:italic toggle=\"yes\">rpoB<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">katG<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">ahpC<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">inhA<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">fabG1<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">embB<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">pncA<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">rpsL<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">rrs<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">gyrA<\/jats:italic>\n                    . The majority of these mutations were identified in relatively high proportions in lineage 1. Our study highlights the utility of whole-genome sequencing as a potential supplemental tool to the existing genotypic and phenotypic methods, in providing expedited comprehensive surveillance of mutations that may be associated with antitubercular drug resistance as well as lineage characterization of\n                    <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                    isolates. Further larger-scale whole-genome datasets with linked minimum inhibition concentration testing are imperative for resolving the discrepancies between whole-genome sequencing and phenotypic drug sensitivity testing results and quantifying the level of the resistance associated with the mutations for optimization of antitubercular drug and precise dose selection in clinics.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Studies mapping genetic heterogeneity of clinical isolates of\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      for determining their strain lineage and drug resistance by whole-genome sequencing are limited in high tuberculosis burden settings. We carried out whole-genome sequencing of 242\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      isolates from drug-sensitive and drug-resistant tuberculosis patients, identified and collected as part of the TB Portals Program, to have a comprehensive insight into the genetic diversity of\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      in Southern India. We report several genetic variations in\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      that may confer resistance to antitubercular drugs. Further wide-scale efforts are required to fully characterize\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      genetic diversity at a population level in high tuberculosis burden settings for providing precise tuberculosis treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.04531-22","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T09:01:49Z","timestamp":1693990909000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Lineage classification and antitubercular drug resistance surveillance of\n                    <i>Mycobacterium tuberculosis<\/i>\n                    by whole-genome sequencing in Southern India"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3322-5399","authenticated-orcid":false,"given":"Mahadev","family":"Rao","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE)","place":["Manipal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4973-9370","authenticated-orcid":false,"given":"Kurt","family":"Wollenberg","sequence":"additional","affiliation":[{"name":"Department of Health and Human Services, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health","place":["Bethesda, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8789-0912","authenticated-orcid":false,"given":"Michael","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Health and Human Services, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health","place":["Bethesda, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrivathsa","family":"Kulavalli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE)","place":["Manipal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1520-9598","authenticated-orcid":false,"given":"Levin","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE)","place":["Manipal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Chawla","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education (MAHE)","place":["Manipal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishnu Prasad","family":"Shenoy","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education (MAHE)","place":["Manipal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muralidhar","family":"Varma","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education (MAHE)","place":["Manipal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavitha","family":"Saravu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education (MAHE)","place":["Manipal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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