Dissecting whole-genome sequencing-based online tools for predicting resistance in Mycobacterium tuberculosis: can we use them for clinical decision guidance?

Tuberculosis
Rita MacedoJoão Paulo Gomes

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...Continue Reading

Citations

Nov 2, 2018·Journal of Clinical Microbiology·Michelle SuTimothy D Read
Jun 25, 2020·Journal of Medical Microbiology·Tryna TaniaKiatichai Faksri
Jun 19, 2019·Nature Reviews. Microbiology·Conor J MeehanAnnelies Van Rie
Jan 29, 2020·International Journal of Antimicrobial Agents·Charlotte GenestetUNKNOWN Lyon TB Study Group

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