| Autor: |
The CRyPTIC Consortium, Barilar, Ivan, Battaglia, Simone, Borroni, Emanuele, Brandao, Angela Pires, Brankin, Alice, Cabibbe, Andrea Maurizio, Carter, Joshua, Chetty, Darren, Cirillo, Daniela Maria, Claxton, Pauline, Clifton, David A., Cohen, Ted, Coronel, Jorge, Crook, Derrick W., Dreyer, Viola, Earle, Sarah G., Escuyer, Vincent, Ferrazoli, Lucilaine, Fowler, Philip W. |
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| Zdroj: |
Nature Communications; 1/12/2024, Vol. 15 Issue 1, p1-13, 13p |
| Abstrakt: |
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. Molecular diagnostics for tuberculosis have focused on predicting drug susceptibilities in a binary manner (i.e., strains are either susceptible or resistant). Here, CRyPTIC Consortium researchers use whole genome sequencing and a quantitative assay to identify associations between genomic mutations and minimum inhibitory concentrations in over 15,000 Mycobacterium tuberculosis clinical isolates. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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