Whole-Genome Sequencing Predicting Phenotypic Antitubercular Drug Resistance: Meta-analysis.

Yoichi Tagami, Nobuyuki Horita, Megumi Kaneko, Suguru Muraoka, Nobuhiko Fukuda, Ami Izawa, Ayami Kaneko, Kohei Somekawa, Chisato Kamimaki, Hiromi Matsumoto, Katsushi Tanaka, Kota Murohashi, Ayako Aoki, Hiroaki Fujii, Keisuke Watanabe, Yu Hara, Nobuaki Kobayashi, Takeshi Kaneko
Author Information
  1. Yoichi Tagami: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  2. Nobuyuki Horita: Chemotherapy Center, Yokohama City University Hospital, Yokohama, Japan. ORCID
  3. Megumi Kaneko: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  4. Suguru Muraoka: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  5. Nobuhiko Fukuda: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  6. Ami Izawa: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  7. Ayami Kaneko: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  8. Kohei Somekawa: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  9. Chisato Kamimaki: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  10. Hiromi Matsumoto: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  11. Katsushi Tanaka: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  12. Kota Murohashi: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  13. Ayako Aoki: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  14. Hiroaki Fujii: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  15. Keisuke Watanabe: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  16. Yu Hara: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  17. Nobuaki Kobayashi: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  18. Takeshi Kaneko: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Abstract

BACKGROUND: For simultaneous prediction of phenotypic drug susceptibility test (pDST) for multiple antituberculosis drugs, the whole genome sequencing (WGS) data can be analyzed using either a catalog-based approach, wherein 1 causative mutation suggests resistance, (eg, World Health Organization catalog) or noncatalog-based approach using complicated algorithm (eg, TB-profiler, machine learning). The aim was to estimate the predictive ability of WGS-based tests with pDST as the reference, and to compare the 2 approaches.
METHODS: Following a systematic literature search, the diagnostic test accuracies for 14 drugs were pooled using a random-effect bivariate model.
RESULTS: Of 779 articles, 44 with 16 821 specimens for meta-analysis and 13 not for meta-analysis were included. The areas under summary receiver operating characteristic curve suggested test accuracy was excellent (0.97-1.00) for 2 drugs (isoniazid 0.975, rifampicin 0.975), very good (0.93-0.97) for 8 drugs (pyrazinamide 0.946, streptomycin 0.952, amikacin 0.968, kanamycin 0.963, capreomycin 0.965, para-aminosalicylic acid 0.959, levofloxacin 0.960, ofloxacin 0.958), and good (0.75-0.93) for 4 drugs (ethambutol 0.926, moxifloxacin 0.896, ethionamide 0.878, prothionamide 0.908). The noncatalog-based and catalog-based approaches had similar ability for all drugs.
CONCLUSIONS: WGS accurately identifies isoniazid and rifampicin resistance. For most drugs, positive WGS results reliably predict pDST positive. The 2 approaches had similar ability.
CLINICAL TRIALS REGISTRATION: UMIN-ID UMIN000049276.

Keywords

MeSH Term

Humans
Antitubercular Agents
Drug Resistance, Bacterial
Isoniazid
Microbial Sensitivity Tests
Mycobacterium tuberculosis
Phenotype
Rifampin
Tuberculosis, Multidrug-Resistant
Whole Genome Sequencing

Chemicals

Antitubercular Agents
Isoniazid
Rifampin

Word Cloud

Created with Highcharts 10.0.00drugstestpDSTWGSusingability2approachessequencingcatalog-basedapproachresistanceegnoncatalog-basedsystematicmeta-analysisisoniazid975rifampicingoodsimilarpositiveBACKGROUND:simultaneouspredictionphenotypicdrugsusceptibilitymultipleantituberculosiswholegenomedatacananalyzedeitherwherein1causativemutationsuggestsWorldHealthOrganizationcatalogcomplicatedalgorithmTB-profilermachinelearningaimestimatepredictiveWGS-basedtestsreferencecompareMETHODS:Followingliteraturesearchdiagnosticaccuracies14pooledrandom-effectbivariatemodelRESULTS:779articles4416821specimens13includedareassummaryreceiveroperatingcharacteristiccurvesuggestedaccuracyexcellent97-10093-0978pyrazinamide946streptomycin952amikacin968kanamycin963capreomycin965para-aminosalicylicacid959levofloxacin960ofloxacin95875-0934ethambutol926moxifloxacin896ethionamide878prothionamide908CONCLUSIONS:accuratelyidentifiesresultsreliablypredictCLINICALTRIALSREGISTRATION:UMIN-IDUMIN000049276Whole-GenomeSequencingPredictingPhenotypicAntitubercularDrugResistance:Meta-analysisMycobacteriuminfectionsDNAanalysisantibacterialagentreview

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