ArticleAmerican journal of respiratory and critical care medicine2016
Genetic Determinants of Drug Resistance in Mycobacterium tuberculosis and Their Diagnostic Value.
Article in American journal of respiratory and critical care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04923958 (Rapid Research in Diagnostics Development for TB Network), which is not on this map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) Study
Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.
- Systematic review of mutations associated with resistance to the new and repurposed Mycobacterium tuberculosis drugs bedaquiline, clofazimine, linezolid, delamanid and pretomanid.The Journal of antimicrobial chemotherapy · 2020Pooled it
- The structural context of mutations in proteins predicts their effect on antibiotic resistance.eLife · 2026Article
- ALPAR: automated learning pipeline for antimicrobial resistance.Bioinformatics (Oxford, England) · 2026Article
- A Comprehensive Review of Genetic Mechanisms ofInfection and drug resistance · 2026Review
- Mutations inInfection and drug resistance · 2026Article
- An explainable artificial intelligence framework reveals mutations associated with drug resistance inBiosafety and health · 2025Article
- Enhanced diagnosis of multi-drug-resistant microbes using group association modeling and machine learning.Nature communications · 2025Article
- Multivariable regression models improve accuracy and sensitive grading of antibiotic resistance mutations in Mycobacterium tuberculosis.Nature communications · 2025Article
- Drug Resistance and Epidemiological Success of Modern Mycobacterium tuberculosis Lineages in Western India.The Journal of infectious diseases · 2025Article
- Feature selection and aggregation for antibiotic resistance GWAS inFrontiers in microbiology · 2025Article
- Drug-resistant tuberculosis: a persistent global health concern.Nature reviews. Microbiology · 2024Review
- Pan-lineage Mycobacterium tuberculosis reference genome for enhanced molecular diagnosis.DNA research : an international journal for rapid publication of reports on genes and genomes · 2024Article
- Development of a multiplex droplet digital PCR method for detection and monitoring of Mycobacterium tuberculosis and drug-resistant tuberculosis.Annals of clinical microbiology and antimicrobials · 2024Article
- Estimation of country-specific tuberculosis resistance antibiograms using pathogen genomics and machine learning.BMJ global health · 2024Article
- Deep learning for precise diagnosis and subtype triage of drug-resistant tuberculosis on chest computed tomography.MedComm · 2024Article
- TB-DROP: deep learning-based drug resistance prediction of Mycobacterium tuberculosis utilizing whole genome mutations.BMC genomics · 2024Article
- Comparison of Nucleotide MALDI-TOF MS with Xpert MTB/RIF for Rifampicin Susceptibility Identification and Associated Risk Factors of Rifampicin Resistance Among Drug ResistantInfection and drug resistance · 2024Article
- Omics analysis of Mycobacterium tuberculosis isolates uncovers Rv3094c, an ethionamide metabolism-associated gene.Communications biology · 2023Article
- Article
- Tools to Alleviate the Drug Resistance inMolecules (Basel, Switzerland) · 2022Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 13 institutions in 7 countries.
Funding
Abstract
rationaleThe development of molecular diagnostics that detect both the presence of Mycobacterium tuberculosis in clinical samples and drug resistance-conferring mutations promises to revolutionize patient care and interrupt transmission by ensuring early diagnosis. However, these tools require the identification of genetic determinants of resistance to the full range of antituberculosis drugs.
objectivesTo determine the optimal molecular approach needed, we sought to create a comprehensive catalog of resistance mutations and assess their sensitivity and specificity in diagnosing drug resistance.
methodsWe developed and validated molecular inversion probes for DNA capture and deep sequencing of 28 drug-resistance loci in M. tuberculosis. We used the probes for targeted sequencing of a geographically diverse set of 1,397 clinical M. tuberculosis isolates with known drug resistance phenotypes. We identified a minimal set of mutations to predict resistance to first- and second-line antituberculosis drugs and validated our predictions in an independent dataset. We constructed and piloted a web-based database that provides public access to the sequence data and prediction tool. MEASUREMENTS AND MAIN
resultsThe predicted resistance to rifampicin and isoniazid exceeded 90% sensitivity and specificity but was lower for other drugs. The number of mutations needed to diagnose resistance is large, and for the 13 drugs studied it was 238 across 18 genetic loci.
conclusionsThese data suggest that a comprehensive M. tuberculosis drug resistance diagnostic will need to allow for a high dimension of mutation detection. They also support the hypothesis that currently unknown genetic determinants, potentially discoverable by whole-genome sequencing, encode resistance to second-line tuberculosis drugs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.