Dissecting whole-genome sequencing-based online tools for predicting resistance in Mycobacterium tuberculosis: can we use them for clinical decision guidance?. (May 2018)

• Record Type: Journal Article
• Authors: Macedo, Rita; Nunes, Alexandra; Portugal, Isabel; Duarte, Sílvia; Vieira, Luís; Gomes, João Paulo
• Is Part Of: Tuberculosis. Volume 110(2018)
• Page Start: 44
• Page End: 51
• Publication Date: 2018-05
• Subjects: Multidrug-resistant tuberculosis -- Whole-genome sequencing -- TB profiler -- TGS-TB -- PhyResSE -- Mykrobe predictor; AMK Amikacin -- CAP Capreomycin -- CICLO Cicloserine -- DST Drug Susceptibility Testing -- EMB Etambutol -- ETH Ethionamide -- FLQ Fluoroquinolones -- IGV Integrative Genomics Viewer -- INH Isoniazid -- KAN Kanamycin -- LNZ Linezolid -- MDR-TB Multidrug-resistant Tuberculosis -- MOX Moxifloxacin -- MTBC Mycobacterium tuberculosis complex -- NPV Negative Predicted Value -- OFX Ofloxacin -- PAS Para-aminosalicylic acid -- PPV Positive Predicted Value -- PZA Pyrazinamide -- RMP Rifampicin -- SNP Single Nucleotide Polymorphisms -- SRA Sequence Read Archive -- STR Streptomycine -- TB Tuberculosis -- WGS Whole genome sequencing -- WHO World Health Organization -- XDR-TB Extensively drug-resistant Tuberculosis; 616.995
• DOI: 10.1016/j.tube.2018.03.009
• Languages: English
• ISSNs: 1472-9792

Abstract

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 rps L 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.