{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:23:35Z","timestamp":1790540615816,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T00:00:00Z","timestamp":1588118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R56 AI118361"],"award-info":[{"award-number":["R56 AI118361"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI063200"],"award-info":[{"award-number":["R01 AI063200"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K24 065298"],"award-info":[{"award-number":["K24 065298"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K01 AI131895"],"award-info":[{"award-number":["K01 AI131895"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K08 AI106420"],"award-info":[{"award-number":["K08 AI106420"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Fluoroquinolone resistance in Mycobacterium tuberculosis (Mtb) is conferred by DNA gyrase mutations, but not all fluoroquinolone-resistant Mtb isolates have mutations detected. The optimal allele frequency threshold to identify resistance-conferring mutations by whole-genome sequencing is unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Phenotypically ofloxacin-resistant and lineage-matched ofloxacin-susceptible Mtb isolates underwent whole-genome sequencing at an average coverage depth of 868 reads. Polymorphisms within the quinolone-resistance\u2013determining region (QRDR) of gyrA and gyrB were identified. The allele frequency threshold using the Genome Analysis Toolkit pipeline was ~8%; allele-level data identified the predominant variant allele frequency and mutational burden (ie, sum of all variant allele frequencies in the QRDR) in gyrA, gyrB, and gyrA + gyrB for each isolate. Receiver operating characteristic (ROC) curves assessed the optimal measure of allele frequency and potential thresholds for identifying phenotypically resistant isolates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 42 ofloxacin-resistant Mtb isolates, area under the ROC curve (AUC) was highest for predominant variant allele frequency, so that measure was used to evaluate optimal mutation detection thresholds. AUCs for 8%, 2.5%, and 0.8% thresholds were 0.8452, 0.9286, and 0.9069, respectively. Sensitivity and specificity were 69% and 100% for 8%, 86% and 100% for 2.5%, 91% and 91% for 0.8%. The sensitivity of the 2.5% and 0.8% thresholds were significantly higher than the 8% threshold (P = .016 and .004, respectively) but not significantly different between one another (P = .5).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A predominant mutation allele frequency threshold of 2.5% had the highest AUC for detecting DNA gyrase mutations that confer ofloxacin resistance, and was therefore the optimal threshold.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciaa496","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T19:09:49Z","timestamp":1587755389000},"page":"1910-1918","source":"Crossref","is-referenced-by-count":12,"title":["Resistance-Conferring Mutations on Whole-Genome Sequencing of Fluoroquinolone-resistant and -Susceptible <i>Mycobacterium tuberculosis<\/i> Isolates: A Proposed Threshold for Identifying Resistance"],"prefix":"10.1093","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9533-8239","authenticated-orcid":false,"given":"Fernanda","family":"Maruri","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"},{"name":"Vanderbilt Tuberculosis Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amondrea","family":"Blackman","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"},{"name":"Vanderbilt Tuberculosis Center, Vanderbilt 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