{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:58:47Z","timestamp":1787320727243,"version":"build-2736575974"},"reference-count":35,"publisher":"Microbiology Society","issue":"12","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018336","name":"National Institute for Health Research Health Protection Research Unit","doi-asserted-by":"crossref","award":["NIHR200915"],"award-info":[{"award-number":["NIHR200915"]}],"id":[{"id":"10.13039\/100018336","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,15]]},"abstract":"<jats:p>\n                    Tuberculosis remains a global health problem. Making it easier and quicker to identify which antibiotics an infection is likely to be susceptible to will be a key part of the solution. Whilst whole-genome sequencing offers many advantages, the processing of the genetic reads to produce the relevant public health and clinical information is, surprisingly, often the responsibility of the end user, which inhibits uptake. Here, we characterize how well a freely available tool we have developed, gnomonicus, predicts the antibiotic resistance profile of a sample (given its variant call file) using our implementation of the second edition of the World Health Organization (WHO) catalogue of resistance-associated variants (WHOv2). To facilitate this, we have constructed a diverse test set of 2,663 publicly available\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    samples, which have both genetic and drug susceptibility testing (DST) data. We have chosen to apply the catalogue such that our tool will return a result of (i) Fail if there are insufficient reads at a genetic locus associated with resistance, (ii) Unknown if a genetic variant in a resistance gene not listed in the catalogue is encountered and (iii) Resistant if three or more short-reads support the presence of a resistance-associated variant. The last step increases the sensitivity for all 15 antibiotics but only reaches significance in a few in our test set. Comparing our results with those of TB-Profiler, an existing tool, highlights the different design choices and demonstrates that the performance of both tools on our diverse test set is comparable. By only considering high-confidence DST results, we show that gnomonicus, in combination with our translation of WHOv2, achieves sensitivities and specificities in excess of 95% for both isoniazid and rifampicin.\n                  <\/jats:p>","DOI":"10.1099\/mgen.0.001592","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T17:17:20Z","timestamp":1765819040000},"source":"Crossref","is-referenced-by-count":5,"title":["Characterizing the performance of an antibiotic resistance prediction tool, gnomonicus, using a diverse test set of 2,663 Mycobacterium tuberculosis samples"],"prefix":"10.1099","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0660-7827","authenticated-orcid":false,"given":"Jeremy","family":"Westhead","sequence":"first","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8135-2652","authenticated-orcid":false,"given":"Catriona S.","family":"Baker","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6758-2194","authenticated-orcid":false,"given":"Marc","family":"Brouard","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2219-4084","authenticated-orcid":false,"given":"Matthew","family":"Colpus","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3480-3819","authenticated-orcid":false,"given":"Bede","family":"Constantinides","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9899-6289","authenticated-orcid":false,"given":"Alexandra","family":"Hall","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1206-0583","authenticated-orcid":false,"given":"Jeff","family":"Knaggs","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6848-7837","authenticated-orcid":false,"given":"Marcela Lopes","family":"Alves","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1584-9141","authenticated-orcid":false,"given":"Ruan","family":"Spies","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3747-8679","authenticated-orcid":false,"given":"Hieu","family":"Thai","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Surrall","sequence":"additional","affiliation":[{"name":"Ellison Institute of Technology, Oxford Ltd, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9208-4376","authenticated-orcid":false,"given":"Kumeren","family":"Govender","sequence":"additional","affiliation":[{"name":"Ellison Institute of Technology, Oxford Ltd, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy E.A.","family":"Peto","sequence":"additional","affiliation":[{"name":"Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, John Radcliffe Hospital, Oxford, UK"},{"name":"National Institute of Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK"},{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0590-2850","authenticated-orcid":false,"given":"Derrick W.","family":"Crook","sequence":"additional","affiliation":[{"name":"National Institute of Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK"},{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"},{"name":"Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, John Radcliffe Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6983-1636","authenticated-orcid":false,"given":"Shaheed V.","family":"Omar","sequence":"additional","affiliation":[{"name":"Centre for Tuberculosis, National & WHO Supranational TB Reference Laboratory, National, Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1353-1404","authenticated-orcid":false,"given":"Robert","family":"Turner","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0912-4483","authenticated-orcid":false,"given":"Philip W.","family":"Fowler","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"},{"name":"Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, John Radcliffe Hospital, Oxford, UK"},{"name":"National Institute of Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","article-title":"Data and code to reproducible results and figures","author":"Westhead","year":"2025"},{"key":"R2","volume-title":"Global Tuberculosis Report, ISBN: 978-92-4-010153-1","year":"2024"},{"key":"R3","article-title":"Rapid communication: key changes to the treatment of drug-resistant tuberculosis","year":"2022"},{"key":"R4","volume-title":"WHO Bacterial Priority Pathogens List: Bacterial Pathogens of Public Health Importance to Guide Research, Development and Strategies to Prevent and Control Antimicrobial Resistance, ISBN: 978-92-4-009346-1","year":"2024"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30123-8"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001721"},{"key":"R7","volume-title":"Catalogue of Mutations in Mycobacterium tuberculosis Complex and Their Association with Drug Resistance, ISBN: 978-92-4-002817-3","year":"2021"},{"key":"R8","volume-title":"Catalogue of Mutations in Mycobacterium tuberculosis Complex and Their Association with Drug Resistance, 2nd ed. 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Clinical Laboratory Testing and in Vitro Diagnostic Test Systems - Susceptibility Testing of Infectious Agents and Evaluation of Performance of Antimicrobial Susceptibility Test Devices. 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