Rapid determination of antituberculosis drug resistance from wholegenome sequences.

Francesc Coll, Ruth McNerney, Mark D. Preston, José Afonso Guerra-Assunção, Andrew Warry, Grant Hill-Cawthorne, Kim Mallard, Mridul Nair, Anabela Miranda, Adriana Alves, João Perdigão, M Viveiros, Isabel Portugal, Zahra Hasan, Rumina Hasan, Judith R. Glynn, Nigel Martin, Arnab Pain, Taane G. Clark

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
JournalGenome Medicine
DOIs
Publication statusPublished - 2015

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