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Diagnosis of Drug-Resistant Tuberculosis: Rapid Evaluation of Drug Susceptibility with Nanopore Targeted Sequencing.

Background Whole-genome sequencing (WGS) has limitations in clinical diagnostics due to host DNA interference and lower pathogen load in clinical samples compared to cultured isolates, which reduce the effective sequencing depth and compromise the detection of resistance-associated mutations. As our...

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Published in:Clinical Chemistry Vol. 71; no. 8; pp. 908 - 920
Main Authors: Chen, Jun, Fan, Qijing, Gong, Shiwei, Guo, Jianjian, Rao, Youyi, Chen, Lifeng, Wang, Ying, Liao, Rui, Zhang, Zhengbin, Liu, Chang, Wu, Ming, Chen, Shi, Ren, Yi
Format: Journal Article
Published: Oxford University Press / USA Aug2025
Online Access:View this record in EBSCOhost
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      jtl: Clinical Chemistry
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      dt: Aug2025
      vid: 71
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      pub: Oxford University Press / USA
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        187168677
        10.1093/clinchem/hvaf061
        187168677
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        atl: Diagnosis of Drug-Resistant Tuberculosis: Rapid Evaluation of Drug Susceptibility with Nanopore Targeted Sequencing.
      aug:
        au:
          Chen, Jun
          Fan, Qijing
          Gong, Shiwei
          Guo, Jianjian
          Rao, Youyi
          Chen, Lifeng
          Wang, Ying
          Liao, Rui
          Zhang, Zhengbin
          Liu, Chang
          Wu, Ming
          Chen, Shi
          Ren, Yi
        affil: Department of Laboratory Medicine, Wuhan Pulmonary Hospital, Wuhan, China
      sug:
      ab: Background Whole-genome sequencing (WGS) has limitations in clinical diagnostics due to host DNA interference and lower pathogen load in clinical samples compared to cultured isolates, which reduce the effective sequencing depth and compromise the detection of resistance-associated mutations. As our understanding of the relationship between genotypes and phenotypes improves, targeted next-generation sequencing (tNGS) is emerging as a promising tool for predicting drug resistance in Mycobacterium tuberculosis. This study aimed to evaluate the performance of nanopore targeted sequencing (NTS) in detecting drug resistance in Mycobacterium tuberculosis. Methods We employed NTS to assess the drug susceptibility of 105 M. tuberculosis isolates and 175 clinical samples to 15 antituberculosis (TB) drugs, using phenotypic drug susceptibility testing as the gold standard. Results For cultured isolates, the overall sensitivity of NTS for 15 anti-TB drugs was 90.2% (95% CI, 86.5–93.2%), specificity 95.6% (94.2–96.8%), positive predictive value (PPV) 86.8% (83.1–89.8%), negative predictive value (NPV) 96.9% (95.7–97.7%), and overall agreement 94.3% (93.0–95.5%). The Cohen Kappa was 0.847 (0.814–0.880). For direct clinical samples, the sensitivity was 93.2% (89.5–95.9%), specificity 98.6% (98.0–99.1%), PPV 89.9% (86.0–92.8%), NPV 99.1% (98.6–99.4%), and agreement 98.0% (97.3–98.5%), with a Cohen Kappa value of 0.904 (0.876–0.931). NTS demonstrated a limit of detection of 500 copies/mL and could detect 4% heteroresistance. Conclusions NTS is a rapid and efficient diagnostic tool that reliably predicts drug resistance and shows potential to support resistance profiling in the clinical setting.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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