Robust detection of point mutations involved in multidrug-resistant Mycobacterium tuberculosis in the presence of co-occurrent resistance markers

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dc.contributor.authorLibiseller-Egger, Julian
dc.contributor.authorPhelan, Jody
dc.contributor.authorCampino, Susana
dc.contributor.authorMohareb, Fady
dc.contributor.authorClark, Taane G.
dc.date.accessioned2021-01-21T14:56:28Z
dc.date.available2021-01-21T14:56:28Z
dc.date.issued2020-12-21
dc.description.abstractTuberculosis disease is a major global public health concern and the growing prevalence of drug-resistant Mycobacterium tuberculosis is making disease control more difficult. However, the increasing application of whole-genome sequencing as a diagnostic tool is leading to the profiling of drug resistance to inform clinical practice and treatment decision making. Computational approaches for identifying established and novel resistance-conferring mutations in genomic data include genome-wide association study (GWAS) methodologies, tests for convergent evolution and machine learning techniques. These methods may be confounded by extensive co-occurrent resistance, where statistical models for a drug include unrelated mutations known to be causing resistance to other drugs. Here, we introduce a novel ‘cannibalistic’ elimination algorithm (“Hungry, Hungry SNPos”) that attempts to remove these co-occurrent resistant variants. Using an M. tuberculosis genomic dataset for the virulent Beijing strain-type (n=3,574) with phenotypic resistance data across five drugs (isoniazid, rifampicin, ethambutol, pyrazinamide, and streptomycin), we demonstrate that this new approach is considerably more robust than traditional methods and detects resistance-associated variants too rare to be likely picked up by correlation-based techniques like GWASen_UK
dc.identifier.citationLibiseller-Egger J, Phelan J, Campino S, et al., (2020) Robust detection of point mutations involved in multidrug-resistant Mycobacterium tuberculosis in the presence of co-occurrent resistance markers. PLoS Computational Biology, Volume 16, Issue 12, 2020, Article number e1008518en_UK
dc.identifier.issn1553-734X
dc.identifier.urihttps://doi.org/10.1371/journal.pcbi.1008518
dc.identifier.urihttp://dspace.lib.cranfield.ac.uk/handle/1826/16217
dc.language.isoenen_UK
dc.publisherPLOS (Public Library of Science)en_UK
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectMycobacterium tuberculosisen_UK
dc.subjectgenome-wide association studyen_UK
dc.titleRobust detection of point mutations involved in multidrug-resistant Mycobacterium tuberculosis in the presence of co-occurrent resistance markersen_UK
dc.typeArticleen_UK

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