학술논문

A data compendium associating the genomes of 12,289 Mycobacterium tuberculosis isolates with quantitative resistance phenotypes to 13 antibiotics.
Document Type
Article
Source
PLoS Biology. 8/9/2022, Vol. 20 Issue 8, p1-25. 25p. 1 Diagram, 3 Charts, 4 Graphs, 1 Map.
Subject
*MYCOBACTERIUM tuberculosis
*PHARMACOGENOMICS
*ANTIBIOTICS
*ANTITUBERCULAR agents
*PHENOTYPES
*GENOMES
Language
ISSN
1544-9173
Abstract
The Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) presents here a data compendium of 12,289 Mycobacterium tuberculosis global clinical isolates, all of which have undergone whole-genome sequencing and have had their minimum inhibitory concentrations to 13 antitubercular drugs measured in a single assay. It is the largest matched phenotypic and genotypic dataset for M. tuberculosis to date. Here, we provide a summary detailing the breadth of data collected, along with a description of how the isolates were selected, collected, and uniformly processed in CRyPTIC partner laboratories across 23 countries. The compendium contains 6,814 isolates resistant to at least 1 drug, including 2,129 samples that fully satisfy the clinical definitions of rifampicin resistant (RR), multidrug resistant (MDR), pre-extensively drug resistant (pre-XDR), or extensively drug resistant (XDR). The data are enriched for rare resistance-associated variants, and the current limits of genotypic prediction of resistance status (sensitive/resistant) are presented by using a genetic mutation catalogue, along with the presence of suspected resistance-conferring mutations for isolates resistant to the newly introduced drugs bedaquiline, clofazimine, delamanid, and linezolid. Finally, a case study of rifampicin monoresistance demonstrates how this compendium could be used to advance our genetic understanding of rare resistance phenotypes. The data compendium is fully open source and it is hoped that it will facilitate and inspire future research for years to come. This study by the CRyPTIC consortium presents an open-source dataset of 12,289 Mycobacterium tuberculosis clinical isolates from 23 countries on five continents. To facilitate faster and more targeted treatment of drug-resistant tuberculosis, the authors determined the genomic sequence and susceptibility profile for 13 drugs of each isolate. [ABSTRACT FROM AUTHOR]