ArticleGenome medicine2016
The variability and reproducibility of whole genome sequencing technology for detecting resistance to anti-tuberculous drugs.
Article in Genome medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 61 citations in OpenAlex.
- Open-access genomic drug resistance prediction tools forJournal of clinical microbiology · 2026Pooled it
- Reporting practices for genomic epidemiology of tuberculosis: a systematic review of the literature using STROME-ID guidelines as a benchmark.The Lancet. Microbe · 2021Pooled it
- Variation in multiple classes of simple sequence repeats can alter drug susceptibility inbioRxiv : the preprint server for biology · 2026Article
- Whole-genome sequencing suggests recent transmission of rifampicin-resistant tuberculosis in Botswana.BMC infectious diseases · 2026Article
- Exploring transmission dynamics in epidemiologically linked pulmonary tuberculosis cases and household contacts: a WGS-based investigation.BMC genomics · 2025Article
- Longitudinal phenotypic and genomic evidence revealing increased risk of drug resistance accumulation in tuberculosis patients in the counties of central China.Microbiology spectrum · 2025Article
- The T120P or M172V mutation onEmerging microbes & infections · 2024Article
- Large-scale statistical analysis of Mycobacterium tuberculosis genome sequences identifies compensatory mutations associated with multi-drug resistance.Scientific reports · 2024Article
- Phenotype versus genotype discordant rifampicin susceptibility testing in tuberculosis: implications for a diagnostic accuracy.Microbiology spectrum · 2024Article
- Whole-genome sequencing-based genetic diversity, transmission dynamics, and drug-resistant mutations inFrontiers in public health · 2024Article
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- Epidemiological cut-off values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing ofThe European respiratory journal · 2022Article
- Combined Locked Nucleic Acid Probes and High-Resolution Melting Curve Analysis for Detection of Rifampicin-Resistant Tuberculosis in Northern Thailand.Diagnostics (Basel, Switzerland) · 2022Article
- Genomic epidemiological analysis of Klebsiella pneumoniae from Portuguese hospitals reveals insights into circulating antimicrobial resistance.Scientific reports · 2022Article
- Characterisation of drug-resistant Mycobacterium tuberculosis mutations and transmission in Pakistan.Scientific reports · 2022Article
- Artificial Intelligence and Cardiovascular Genetics.Life (Basel, Switzerland) · 2022Review
- Decreased Methylenetetrahydrofolate Reductase Activity Leads to Increased Sensitivity toAntimicrobial agents and chemotherapy · 2022Article
- The whole-genome sequencing in predicting Mycobacterium tuberculosis drug susceptibility and resistance in Papua, Indonesia.BMC genomics · 2021Article
- Evaluation of whole-genome sequence data analysis approaches for short- and long-read sequencing ofMicrobial genomics · 2021Article
- Effectiveness of GenoType MTBDRThe international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2021Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundThe emergence of resistance to anti-tuberculosis drugs is a serious and growing threat to public health. Next-generation sequencing is rapidly gaining traction as a diagnostic tool for investigating drug resistance in Mycobacterium tuberculosis to aid treatment decisions. However, there are few little data regarding the precision of such sequencing for assigning resistance profiles.
methodsWe investigated two sequencing platforms (Illumina MiSeq, Ion Torrent PGM™) and two rapid analytic pipelines (TBProfiler, Mykrobe predictor) using a well characterised reference strain (H37Rv) and clinical isolates from patients with tuberculosis resistant to up to 13 drugs. Results were compared to phenotypic drug susceptibility testing. To assess analytical robustness individual DNA samples were subjected to repeated sequencing.
resultsThe MiSeq and Ion PGM systems accurately predicted drug-resistance profiles and there was high reproducibility between biological and technical sample replicates. Estimated variant error rates were low (MiSeq 1 per 77 kbp, Ion PGM 1 per 41 kbp) and genomic coverage high (MiSeq 51-fold, Ion PGM 53-fold). MiSeq provided superior coverage in GC-rich regions, which translated into incremental detection of putative genotypic drug-specific resistance, including for resistance to para-aminosalicylic acid and pyrazinamide. The TBProfiler bioinformatics pipeline was concordant with reported phenotypic susceptibility for all drugs tested except pyrazinamide and para-aminosalicylic acid, with an overall concordance of 95.3%. When using the Mykrobe predictor concordance with phenotypic testing was 73.6%.
conclusionsWe have demonstrated high comparative reproducibility of two sequencing platforms, and high predictive ability of the TBProfiler mutation library and analytical pipeline, when profiling resistance to first- and second-line anti-tuberculosis drugs. However, platform-specific variability in coverage of some genome regions may have implications for predicting resistance to specific drugs. These findings may have implications for future clinical practice and thus deserve further scrutiny, set within larger studies and using updated mutation libraries.
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