Rapid determination of antituberculosis drug resistance from wholegenome sequences.

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 l...

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Bibliographic Details
Main Author: Coll, Francesc (author)
Other Authors: McNerney, Ruth (author), Preston, Mark D. (author), Guerra-Assunção, José Afonso (author), Warry, Andrew (author), Hill-Cawthorne, Grant (author), Mallard, Kim (author), Nair, Mridul (author), Miranda, Anabela (author), Alves, Adriana (author), Perdigão, João (author), Viveiros, M (author), Portugal, Isabel (author), Hasan, Zahra (author), Hasan, Rumina (author), Glynn, Judith R. (author), Martin, Nigel (author), Pain, Arnab (author), Clark, Taane G. (author)
Format: article
Language:eng
Published: 2018
Subjects:
SDG 3 - Good Health and Well-being
Online Access:http://hdl.handle.net/10362/37000
Country:Portugal
Oai:oai:run.unl.pt:10362/37000
Description
Summary: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.

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