Dissecting whole-genome sequencing-based online tools for predicting resistance in Mycobacterium tuberculosis: can we use them for clinical decision guidance? - 18/05/18
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Abstract |
Whole-genome sequencing (WGS)-based bioinformatics platforms for the rapid prediction of resistance will soon be implemented in the Tuberculosis (TB) laboratory, but their accuracy assessment still needs to be strengthened. Here, we fully-sequenced a total of 54 multidrug-resistant (MDR) and five susceptible TB strains and performed, for the first time, a simultaneous evaluation of the major four free online platforms (TB Profiler, PhyResSE, Mykrobe Predictor and TGS-TB).
Overall, the sensitivity of resistance prediction ranged from 84.3% using Mykrobe predictor to 95.2% using TB profiler, while specificity was higher and homogeneous among platforms. TB profiler revealed the best performance robustness (sensitivity, specificity, PPV and NPV above 95%), followed by TGS-TB (all parameters above 90%). We also observed a few discrepancies between phenotype and genotype, where, in some cases, it was possible to pin-point some “candidate” mutations (e.g., in the rpsL promoter region) highlighting the need for their confirmation through mutagenesis assays and potential review of the anti-TB genetic databases.
The rampant development of the bioinformatics algorithms and the tremendously reduced time-frame until the clinician may decide for a definitive and most effective treatment will certainly trigger the technological transition where WGS-based bioinformatics platforms could replace phenotypic drug susceptibility testing for TB.
Le texte complet de cet article est disponible en PDF.Keywords : Multidrug-resistant tuberculosis, Whole-genome sequencing, TB profiler, TGS-TB, PhyResSE, Mykrobe predictor
Abbreviations : AMK, CAP, CICLO, DST, EMB, ETH, FLQ, IGV, INH, KAN, LNZ, MDR-TB, MOX, MTBC, NPV, OFX, PAS, PPV, PZA, RMP, SNP, SRA, STR, TB, WGS, WHO, XDR-TB
Plan
Vol 110
P. 44-51 - mai 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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