Rapid determination of anti-tuberculosis drug resistance from whole-genome 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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Detalhes bibliográficos
Autor principal: Coll, Francesc (author)
Outros Autores: 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, Miguel (author), Portugal, Isabel (author), Hasan, Zahra (author), Hasan, Rumina (author), Glynn, Judith R. (author), Martin, Nigel (author), Pain, Arnab (author), Clark, Taane G. (author)
Formato: article
Idioma:eng
Publicado em: 2016
Assuntos:
Tuberculosis
Drug Resistance
Whole Genome Sequences
Infecções Respiratórias
Texto completo:http://hdl.handle.net/10400.18/3554
País:Portugal
Oai:oai:repositorio.insa.pt:10400.18/3554
Descrição
Resumo: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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