In:
Nature Communications, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2024-01-12)
Abstract:
The World Health Organization has a goal of universal drug susceptibility testing for patients with tuberculosis. However, molecular diagnostics to date have focused largely on first-line drugs and predicting susceptibilities in a binary manner (classifying strains as either susceptible or resistant). Here, we used a multivariable linear mixed model alongside whole genome sequencing and a quantitative microtiter plate assay to relate genomic mutations to minimum inhibitory concentration (MIC) in 15,211 Mycobacterium tuberculosis clinical isolates from 23 countries across five continents. We identified 492 unique MIC-elevating variants across 13 drugs, as well as 91 mutations likely linked to hypersensitivity. Our results advance genetics-based diagnostics for tuberculosis and serve as a curated training/testing dataset for development of drug resistance prediction algorithms.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-023-44325-5
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2024
detail.hit.zdb_id:
2553671-0
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