作者
Timothy M Walker, Thomas A Kohl, Shaheed V Omar, Jessica Hedge, Carlos Del Ojo Elias, Phelim Bradley, Zamin Iqbal, Silke Feuerriegel, Katherine E Niehaus, Daniel J Wilson, David A Clifton, Georgia Kapatai, Camilla LC Ip, Rory Bowden, Francis A Drobniewski, Caroline Allix-Béguec, Cyril Gaudin, Julian Parkhill, Roland Diel, Philip Supply, Derrick W Crook, E Grace Smith, A Sarah Walker, Nazir Ismail, Stefan Niemann, Tim EA Peto
发表日期
2015/10/1
期刊
The Lancet infectious diseases
卷号
15
期号
10
页码范围
1193-1202
出版商
Elsevier
简介
Background
Diagnosing drug-resistance remains an obstacle to the elimination of tuberculosis. Phenotypic drug-susceptibility testing is slow and expensive, and commercial genotypic assays screen only common resistance-determining mutations. We used whole-genome sequencing to characterise common and rare mutations predicting drug resistance, or consistency with susceptibility, for all first-line and second-line drugs for tuberculosis.
Methods
Between Sept 1, 2010, and Dec 1, 2013, we sequenced a training set of 2099 Mycobacterium tuberculosis genomes. For 23 candidate genes identified from the drug-resistance scientific literature, we algorithmically characterised genetic mutations as not conferring resistance (benign), resistance determinants, or uncharacterised. We then assessed the ability of these characterisations to predict phenotypic drug-susceptibility testing for an independent validation set of …
学术搜索中的文章
TM Walker, TA Kohl, SV Omar, J Hedge, CDO Elias… - The Lancet infectious diseases, 2015