A data compendium associating the genomes of 12,289 Mycobacterium tuberculosis isolates with quantitative resistance phenotypes to 13 antibiotics

Author:

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.

Funder

Wellcome Trust

Bill and Melinda Gates Foundation

National Institute for Health Research Oxford Biomedical Research Centre

National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance

National Mega Project on Major Infectious Disease Prevention

H2020 Marie Skłodowska-Curie Actions

Unitaid

FAPESP

National Natural Science Foundation of China

Beijing Municipal Science and Technology Commission

Wellcome Trust International Intermediate Fellowship

South African Medical Research Council

the Rhodes Trust and Stanford Medical Scientist Training Program

National Institute for Health Research (NIHR) Health Protection Research Unit in Respiratory Infections at Imperial College London

Fonds de Recherche en Santé du Québec

Research Foundation Flanders

National Research Foundation South Africa

National Institute of Allergy and Infectious Diseases

GOSH

GOSH/ICH Biomedical Research Centre

Oxford Medical Research Council Doctoral Training Partnership

Nuffield Department of Clinical Medicine

Sir Henry Dale Fellowship

The Robertson Foundation

NIHR

Rhodes Trust

UK Research and Innovation

Cancer Research UK

National Institutes of Health

Centers for Disease Control and Prevention

USAID

NIHR Oxford Biomedical Research Centre

Deutsches Zentrum für Infektionsforschung

Public Health Scotland

Division of Intramural Research, National Institute of Allergy and Infectious Diseases

Publisher

Public Library of Science (PLoS)

Subject

General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience

Reference54 articles.

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