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

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

Research output: Contribution to journalArticlepeer-review

169 Scopus citations

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 (US)
JournalGenome Medicine
Volume7
Issue number1
DOIs
StatePublished - May 27 2015

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