title: Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences.
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.
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT UK.
authors.forename: Francesc
authors.initials: F
authors.lastname: Coll
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: McNerney
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT UK.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Preston
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT UK.
authors.forename: José Afonso
authors.initials: JA
authors.lastname: Guerra-Assunção
authors.affiliation: Advanced Data Analysis Centre, University of Nottingham, Wollaton Road, Nottingham, NG8 1BB UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Warry
authors.affiliation: Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia ; Sydney Emerging Infections and Biosecurity Institute and School of Public Health, University of Sydney, Sydney, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Hill-Cawthorne
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT UK.
authors.forename: Kim
authors.initials: K
authors.lastname: Mallard
authors.affiliation: Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
authors.forename: Mridul
authors.initials: M
authors.lastname: Nair
authors.affiliation: Tuberculosis Laboratory, Instituto Nacional de Saude Dr. Ricardo Jorge, Porto, Portugal.
authors.forename: Anabela
authors.initials: A
authors.lastname: Miranda
authors.affiliation: Tuberculosis Laboratory, Instituto Nacional de Saude Dr. Ricardo Jorge, Porto, Portugal.
authors.forename: Adriana
authors.initials: A
authors.lastname: Alves
authors.affiliation: Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Perdigão
authors.affiliation: Grupo de Micobactérias, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.affiliation: Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Portugal
authors.affiliation: Department of Pathology & Microbiology, Aga Khan University Hospital, Karachi, Pakistan.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hasan
authors.affiliation: Department of Pathology & Microbiology, Aga Khan University Hospital, Karachi, Pakistan.
authors.forename: Rumina
authors.initials: R
authors.lastname: Hasan
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT UK ; Karonga Prevention Study, Chilumba, Malawi.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Glynn
authors.affiliation: Department of Computer Science, Birkbeck College, University of London, Malet Street, London, WC1E 7HX UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Martin
authors.affiliation: Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
authors.forename: Arnab
authors.initials: A
authors.lastname: Pain
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT UK.
authors.forename: Taane G
authors.initials: TG
authors.lastname: Clark