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Whole-genome sequencing (WGS) is recommended for predicting drug resistance to guide DR-TB treatment and management. Nevertheless, data are lacking in Taiwan. Phenotypic drug susceptibility testing (DST) of 12 anti-TB drugs was performed for 200 <jats:italic>Mycobacterium tuberculosis<\/jats:italic> isolates. WGS was performed using the Illumina platform. Drug resistance profiles and lineages were predicted in silico using the Total Genotyping Solution for TB (TGS-TB). Using the phenotypic DST results as a reference, WGS-based prediction demonstrated high concordance rates of isoniazid (95.0%), rifampicin (RIF) (98.0%), pyrazinamide (98.5%) and fluoroquinolones (FQs) (99.5%) and 96.0% to 99.5% for second-line injectable drugs (SLIDs); whereas, lower concordance rates of ethambutol (87.5%), streptomycin (88.0%) and ethionamide (84.0%). Furthermore, minimum inhibitory concentrations confirmed that RIF <jats:italic>rpoB<\/jats:italic> S450L, FQs <jats:italic>gyrA<\/jats:italic> D94G and SLIDs <jats:italic>rrs<\/jats:italic> a1401g conferred high resistance levels. Besides, we identified lineage-associated mutations in lineage 1 (<jats:italic>rpoB<\/jats:italic> H445Y and <jats:italic>fabG1<\/jats:italic> c-15t) and predominant lineage 2 (<jats:italic>rpoB<\/jats:italic> S450L and <jats:italic>rpsL<\/jats:italic> K43R). The WGS-based prediction of drug resistance is highly concordant with phenotypic DST results and can provide comprehensive genetic information to guide DR-TB precision therapies in Taiwan.<\/jats:p>","DOI":"10.1038\/s41598-023-29652-3","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T14:06:22Z","timestamp":1676297182000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Whole-genome sequencing-based analyses of drug-resistant Mycobacterium tuberculosis from Taiwan"],"prefix":"10.1038","volume":"13","author":[{"given":"Yu-Xin","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Hung","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Hsuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai-Hua","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruwen","family":"Jou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,13]]},"reference":[{"key":"29652_CR1","unstructured":"WHO. 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