Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences.


Coll, F; McNerney, R; Preston, MD; Guerra-Assunção, JA; Warry, A; Hill-Cawthorne, G; Mallard, K; Nair, M; Miranda, A; Alves, A; Perdigão, J; Viveiros, M; Portugal, I; Hasan, Z; Hasan, R; Glynn, JR; Martin, N; Pain, A; Clark, TG; (2015) Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences. Genome Med, 7 (1). p. 51. ISSN 1756-994X DOI: 10.1186/s13073-015-0164-0

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Abstract

Mycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was compiled and validated for 11 of them using genomic-phenotypic data from 792 strains. A rapid online 'TB-Profiler' tool was developed to report DR and strain-type profiles directly from raw sequences. Using our DR mutation library, in silico diagnostic accuracy was superior to some commercial diagnostics and alternative databases. The library will facilitate sequence-based drug-susceptibility testing.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Research Centre: Antimicrobial Resistance Centre (AMR)
MEIRU
PubMed ID: 26019726
Web of Science ID: 355073700001
URI: http://researchonline.lshtm.ac.uk/id/eprint/2197029

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