Author(s): Macedo, Rita ; Nunes, Alexandra ; Portugal, Isabel ; Duarte, Sílvia ; Vieira, Luís ; Gomes, João Paulo
Date: 2018
Persistent ID: http://hdl.handle.net/10400.18/6253
Origin: Repositório Científico do Instituto Nacional de Saúde
Subject(s): Whole-genome Sequencing; Multidrug-resistant Tuberculosis; TB Profiler; Mykrobe Predictor; PhyResSE; TGS-TB; Infecções Respiratórias
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.
