Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing
Open accessAbstract
BACKGROUND: The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. METHODS: We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance. RESULTS: A total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted. CONCLUSIONS: Genotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.).
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Studies in other areas of medicine have found lower NPVs of even highly sensitive and specific tests in situations where the pretest probability of a disease is high.
“Studies in other areas of medicine have also found lower NPVs of even highly sensitive and specific tests in situations where the pretest probability of a disease is high23,26,27.”
From Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability (2024) · cites this paper as [26]
The Results section (page unavailable) reports that negative predictive value declined as the prevalence of tuberculosis drug resistance increased. The Discussion section (page unavailable) says the assay generally met high sensitivity and specificity targets. The paper does not report studies in other areas of medicine or tests for disease in patients with high pretest probability. (LLM, conf=0.86)
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The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041 · see citing works
Stampy: A statistical algorithm for sensitive and fast mapping of Illumina sequence reads
Lunter, G., & Goodson, M. (2011) · Genome Research · doi:10.1101/gr.111120.110 · Cited by 1,016 · see citing works
Boehme, C. C., Nicol, M. P., Nabeta, P., Michael, J. S., Gotuzzo, E., Tahirli, R., Gler, M. T., Blakemore, R., Worodria, W. O., Gray, C. M., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60438-8 · Cited by 1,010 · see citing works
De novo assembly and genotyping of variants using colored de Bruijn graphs
Iqbal, Z., Cáccamo, M., Turner, I., Flicek, P., & McVean, G. (2012) · Nature Genetics · doi:10.1038/ng.1028 · Cited by 695 · see citing works
Walker, T. M., Kohl, T. A., Omar, S. V., Hedge, J., Elías, C. D. O., Bradley, P., Iqbal, Z., Feuerriegel, S., Niehaus, K. E., Wilson, D. J., et al. (2015) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(15)00062-6 · Cited by 626 · see citing works
Evolution and transmission of drug-resistant tuberculosis in a Russian population
Casali, N., Nikolayevskyy, V., Balabanova, Y., Harris, S. R., Ignatyeva, O. A., Kontsevaya, I., Corander, J., Bryant, J. M., Parkhill, J., Nejentsev, S., et al. (2014) · Nature Genetics · doi:10.1038/ng.2878 · Cited by 465 · see citing works
Votintseva, A. A., Bradley, P., Pankhurst, L. J., Elías, C. D. O., Loose, M., Nilgiriwala, K. S., Chatterjee, A., Smith, E. G., Sanderson, N. D., Walker, T. M., et al. (2017) · Journal of Clinical Microbiology · doi:10.1128/jcm.02483-16 · Cited by 344 · see citing works
Ethambutol resistance in Mycobacterium tuberculosis: critical role of embB mutations
Sreevatsan, S., Stockbauer, K. E., Pan, X., Kreiswirth, B. N., Moghazeh, S. L., Jacobs, W. R., Telenti, A., & Musser, J. M. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.8.1677 · Cited by 335 · see citing works
Miotto, P., Tessema, B., Tagliani, E., Chindelevitch, L., Starks, A. M., Emerson, C., Hanna, D. L., Kim, P. S., Liwski, R., Matteo Zignol, E., et al. (2017) · European Respiratory Journal · doi:10.1183/13993003.01354-2017 · Cited by 329 · see citing works
Pankhurst, L. J., Elías, C. D. O., Votintseva, A. A., Walker, T. M., Cole, K., Davies, J., Fermont, J. M., Gascoyne‐Binzi, D., Kohl, T. A., Kong, C., et al. (2015) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(15)00466-x · Cited by 327 · see citing works
Transmission of Extensively Drug-Resistant Tuberculosis in South Africa
Shah, N., Auld, S. C., Brust, J. C. M., Mathema, B., Ismail, N. A., Moodley, P., Mlisana, K. P., Allana, S., Campbell, A., Mthiyane, T., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1604544 · Cited by 280 · see citing works
Manson, A. L., Cohen, K. A., Abeel, T., Desjardins, C. A., Armstrong, D. T., Barry, C. E., Brand, J., Chapman, S. B., Cho, S.-N., Gabrielian, A. E., et al. (2017) · Nature Genetics · doi:10.1038/ng.3767 · Cited by 279 · see citing works
Rigouts, L., Gumusboga, M., de Rijk, W. B., Nduwamahoro, E., Uwizeye, C., de Jong, B. C., & Deun, A. V. (2013) · Journal of Clinical Microbiology · doi:10.1128/jcm.02741-12 · Cited by 200 · see citing works
Detection of Drug-Resistant Tuberculosis by Xpert MTB/RIF in Swaziland
Sánchez-Padilla, E., Merker, M., Beckert, P., Jochims, F., Dlamini, T., Kahn, P., Bonnet, M., & Niemann, S. (2015) · New England Journal of Medicine · doi:10.1056/nejmc1413930 · Cited by 180 · see citing works
Mycobacterium tuberculosis drug-resistance testing: challenges, recent developments and perspectives
Schön, T., Miotto, P., Köser, C. U., Viveiros, M., Böttger, E. C., & Cambau, E. (2016) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2016.10.022 · Cited by 178 · see citing works
Mycobacterium tuberculosis Pyrazinamide Resistance Determinants: a Multicenter Study
Miotto, P., Cabibbe, A. M., Feuerriegel, S., Casali, N., Drobniewski, F. A., Rodionova, Y., Bakonytė, D., Stakėnas, P., Pimkina, E., AUGUSTYNOWICZ-KOPEĆ, E. M., et al. (2014) · mBio · doi:10.1128/mbio.01819-14 · Cited by 152 · see citing works
A comprehensive characterization of PncA polymorphisms that confer resistance to pyrazinamide
Yadon, A. N., Maharaj, K., Adamson, J., Lai, Y.-P., Sacchettini, J. C., Ioerger, T. R., Rubin, E. J., & Pym, A. S. (2017) · Nature Communications · doi:10.1038/s41467-017-00721-2 · Cited by 118 · see citing works
Heyckendorf, J., Andres, S., Köser, C. U., Olaru, I. D., Schön, T., Sturegård, E., Beckert, P., Schleusener, V., Kohl, T. A., Hillemann, D., et al. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01550-17 · Cited by 107 · see citing works
André, E., Goeminne, L., Colmant, A., Beckert, P., Niemann, S., & Delmée, M. (2016) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2016.12.009 · Cited by 46 · see citing works
Nikolayevskyy, V., Hillemann, D., Richter, E., Ahmed, N., van der Werf, M. J., Ködmön, C., Drobniewski, F. A., Ruesch-Gerdes, S., & ERLTB-Net Network (2016) · PLoS ONE · doi:10.1371/journal.pone.0152926 · Cited by 34 · see citing works
Aiming for zero tuberculosis transmission in low-burden countries
Marais, B. J., Walker, T. M., Cirillo, D. M., Raviglione, M. C., Abubakar, I., van der Werf, M. J., Boehme, C. C., Niemann, S., Castro, K. G., Zumla, A. I., et al. (2017) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(17)30382-x · Cited by 20 · see citing works
Coronel, J., Roper, M. H., Mitchell, S. L., Castillo, E., Gamarra, N., Drobniewski, F. A., Luna, G., Mendoza, A., & Moore, D. (2010) · PubMed · Cited by 13 · see citing works
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Sorted by citations
Furin, J. J., Cox, H. S., & Pai, M. (2019) · The Lancet · doi:10.1016/s0140-6736(19)30308-3 · Cited by 876 · see citing works
Sequencing-based methods and resources to study antimicrobial resistance
Boolchandani, M., D’Souza, A. W., & Dantas, G. A. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0108-4 · Cited by 530 · see citing works
Phelan, J. E., O’Sullivan, D. M., Machado, D., Ramos, J., Oppong, Y. E. A., Campino, S. G., O’Grady, J., McNerney, R., Hibberd, M. L., Viveiros, M., et al. (2019) · Genome Medicine · doi:10.1186/s13073-019-0650-x · Cited by 523 · see citing works
Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline
Nahid, P., Mase, S., Migliori, G. B., Sotgiu, G., Bothamley, G. H., Brożek, J., Cattamanchi, A., Cegielski, J. P., Chen, L., Daley, C. L., et al. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201909-1874st · Cited by 463 · see citing works
Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues
Meehan, C. J., Goig, G. A., Kohl, T. A., Verboven, L., Dippenaar, A., Ezewudo, M. N., Farhat, M. R., Guthrie, J. L., Laukens, K., Miotto, P., et al. (2019) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0214-5 · Cited by 431 · see citing works
Using Genomics to Track Global Antimicrobial Resistance
Hendriksen, R. S., Bortolaia, V., Tate, H. P., Tyson, G. H., Aarestrup, F. M., & McDermott, P. F. (2019) · Frontiers in Public Health · doi:10.3389/fpubh.2019.00242 · Cited by 445 · see citing works
Innovative and rapid antimicrobial susceptibility testing systems
van Belkum, A., Burnham, C. D., Rossen, J. W. A., Mallard, F., Rochas, O., & Dunne, W. M. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0327-x · Cited by 362 · see citing works
Management of drug-resistant tuberculosis
Lange, C. G., Dheda, K. U. J., Chesov, D., Mandalakas, A. M., Udwadia, Z. F., & Horsburgh, C. R. (2019) · The Lancet · doi:10.1016/s0140-6736(19)31882-3 · Cited by 302 · see citing works
Walker, T. M., Miotto, P., Köser, C. U., Fowler, P. W., Knaggs, J., Iqbal, Z., Hunt, M., Chindelevitch, L., Farhat, M. R., Cirillo, D. M., et al. (2022) · The Lancet Microbe · doi:10.1016/s2666-5247(21)00301-3 · Cited by 277 · see citing works
Pathogen Genomics in Public Health
Armstrong, G. L., MacCannell, D., Taylor, J., Carleton, H. A., Neuhaus, E. B., Bradbury, R. S., Posey, J. E., & GWINN, M. L. (2019) · New England Journal of Medicine · doi:10.1056/nejmsr1813907 · Cited by 270 · see citing works
Kim, J. I., Maguire, F., Tsang, K. K., Gouliouris, T., Peacock, S. J., McAllister, T. A., McArthur, A. G., & Beiko, R. G. (2022) · Clinical Microbiology Reviews · doi:10.1128/cmr.00179-21 · Cited by 278 · see citing works
Multidrug-resistant tuberculosis
Dheda, K. U. J., Mirzayev, F., Cirillo, D. M., Udwadia, Z. F., Dooley, K. E., Chang, K. C., Omar, S. V., Reuter, A., Perumal, T., Horsburgh, C. R., et al. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00504-2 · Cited by 255 · see citing works
Drug-resistant tuberculosis: a persistent global health concern
Farhat, M. R., Cox, H. S., Ghanem, M., Denkinger, C. M., Rodrigues, C. S., Aziz, M. S. A. E., Enkh-Amgalan, H., Vambe, D., Ugarte‐Gil, C., Furin, J. J., et al. (2024) · Nature Reviews Microbiology · doi:10.1038/s41579-024-01025-1 · Cited by 261 · see citing works
Drug resistant Tuberculosis: A review
Khawbung, J. L., Nath, D., & Chakraborty, S. (2020) · Comparative Immunology Microbiology and Infectious Diseases · doi:10.1016/j.cimid.2020.101574 · Cited by 252 · see citing works
Application of Next Generation Sequencing in Laboratory Medicine
Zhong, Y., Xu, F., Wu, J., Schubert, J. A., & Li, M. M. (2020) · Annals of Laboratory Medicine · doi:10.3343/alm.2021.41.1.25 · Cited by 216 · see citing works
Anahtar, M. N., Yang, J. H., & Kanjilal, S. (2021) · Journal of Clinical Microbiology · doi:10.1128/jcm.01260-20 · Cited by 214 · see citing works
Kadura, S., King, N. C., Nakhoul, M., Zhu, H., Theron, G., Köser, C. U., & Farhat, M. R. (2020) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkaa136 · Cited by 210 · see citing works
Next Generation and Other Sequencing Technologies in Diagnostic Microbiology and Infectious Diseases
Hilt, E. E., & Ferrieri, P. (2022) · Genes · doi:10.3390/genes13091566 · Cited by 204 · see citing works
Hunt, M., Bradley, P., Lapierre, S. G., Heys, S., Thomsit, M., Hall, M. B., Malone, K. M., Wintringer, P., Walker, T. M., Cirillo, D. M., et al. (2019) · Wellcome Open Research · doi:10.12688/wellcomeopenres.15603.1 · Cited by 198 · see citing works
Library preparation for next generation sequencing: A review of automation strategies
Hess, J. F., Kohl, T. A., Kotrová, M., Rönsch, K., Paprotka, T., Mohr, V., Hutzenlaub, T., Brüggemann, M., Zengerle, R., Niemann, S., et al. (2020) · Biotechnology Advances · doi:10.1016/j.biotechadv.2020.107537 · Cited by 196 · see citing works
Next-Generation Sequencing of Infectious Pathogens
GWINN, M. L., MacCannell, D., & Armstrong, G. L. (2019) · JAMA · doi:10.1001/jama.2018.21669 · Cited by 185 · see citing works
Ali, T., Ahmed, S., & Aslam, M. (2023) · Antibiotics · doi:10.3390/antibiotics12030523 · Cited by 181 · see citing works
Cohen, K. A., Manson, A. L., Desjardins, C. A., Abeel, T., & Earl, A. M. (2019) · Genome Medicine · doi:10.1186/s13073-019-0660-8 · Cited by 158 · see citing works
New developments in tuberculosis diagnosis and treatment
Gill, C. M., Dolan, L., Piggott, L. M., & McLaughlin, A. M. (2022) · Breathe · doi:10.1183/20734735.0149-2021 · Cited by 163 · see citing works
Cabibbe, A. M., Spitaleri, A., Battaglia, S., Colman, R. E., Suresh, A., Uplekar, S. M., Rodwell, T. C., & Cirillo, D. M. (2020) · Journal of Clinical Microbiology · doi:10.1128/jcm.00632-20 · Cited by 143 · see citing works
Diagnosis and treatment of multidrug-resistant tuberculosis
Jang, J. G., & Chung, J. H. (2020) · Yeungnam University Journal of Medicine · doi:10.12701/yujm.2020.00626 · Cited by 140 · see citing works
Struelens, M. J., Ludden, C., Werner, G., Sintchenko, V., Jokelainen, P., & Ip, M. (2024) · Frontiers in Science · doi:10.3389/fsci.2024.1298248 · Cited by 155 · see citing works
Chen, M. L., Doddi, A., Royer, J., Freschi, L., Schito, M. L., Ezewudo, M. N., Kohane, I. S., Beam, A. L., & Farhat, M. R. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.04.016 · Cited by 126 · see citing works
Bhattacharyya, R. P., Bandyopadhyay, N., Ma, P., Son, S. S., Liu, J., He, L. L., Wu, L., Khafizov, R., Boykin, R., Cerqueira, G. C., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0650-9 · Cited by 122 · see citing works
Doyle, R., O’Sullivan, D. M., Aller, S., Bruchmann, S., Clark, T. G., Pelegrin, A. C., Cormican, M., Benavente, E. D., Ellington, M. J., McGrath, E., et al. (2020) · Microbial Genomics · doi:10.1099/mgen.0.000335 · Cited by 120 · see citing works
Lees, J. A., Mai, T., Galardini, M., Wheeler, N. E., Horsfield, S., Parkhill, J., & Corander, J. (2020) · mBio · doi:10.1128/mbio.01344-20 · Cited by 120 · see citing works
New insights into the mycobacterial PE and PPE proteins provide a framework for future research
Ates, L. S. (2019) · Molecular Microbiology · doi:10.1111/mmi.14409 · Cited by 112 · see citing works
The CRyPTIC Consortium (2022) · PLoS Biology · doi:10.1371/journal.pbio.3001721 · Cited by 117 · see citing works
Jouet, A., Gaudin, C., Badalato, N., Allix‐Béguec, C., Duthoy, S., Ferré, A., Diels, M., Laurent, Y., Contreras, S., Feuerriegel, S., et al. (2020) · European Respiratory Journal · doi:10.1183/13993003.02338-2020 · Cited by 114 · see citing works
Recent and emerging technologies for the rapid diagnosis of infection and antimicrobial resistance
Trotter, A. J., Aydin, A., Strinden, M. J., & O’Grady, J. (2019) · Current Opinion in Microbiology · doi:10.1016/j.mib.2019.03.001 · Cited by 113 · see citing works
Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability
Therriault, J., Janelidze, S., Benedet, A. L., Ashton, N. J., Arranz Martínez, J., Gonzalez-Escalante, A., Bellaver, B., Alcolea, D., Vrillon, A., Karim, H., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00731-y · Cited by 112 · see citing works
Dheda, K. U. J., Gumbo, T., Maartens, G., Dooley, K. E., Murray, M. B., Furin, J. J., Nardell, E. A., Warren, R. M., Dheda, K. U. J., Gumbo, T., et al. (2019) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(19)30263-2 · Cited by 112 · see citing works
Chen, X., He, G., Wang, S., Lin, S., Chen, J., & Zhang, W. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.01741 · Cited by 111 · see citing works
Application of machine learning techniques to tuberculosis drug resistance analysis
Kouchaki, S., Yang, Y., Walker, T. M., Walker, A. S., Wilson, D. J., Peto, T., Crook, D. W., & Clifton, D. A. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty949 · Cited by 109 · see citing works
Tuberculosis treatment failure associated with evolution of antibiotic resilience
Liu, Q., Zhu, J., Dulberger, C. L., Stanley, S., Wilson, S., Chung, E. S., Wang, X., Culviner, P. H., Liu, Y. J., Hicks, N. D., et al. (2022) · Science · doi:10.1126/science.abq2787 · Cited by 108 · see citing works
Domínguez, J., Boeree, M. J., Cambau, E., Chesov, D., Conradie, F., Cox, V., Dheda, K., Dudnyk, A., Farhat, M. R., Gagneux, S., et al. (2023) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(22)00875-1 · Cited by 99 · see citing works
Nimmo, C., Shaw, L. P., Doyle, R., Williams, R. J., Brien, K., Burgess, C., Breuer, J., Balloux, F., & Pym, A. S. (2019) · BMC Genomics · doi:10.1186/s12864-019-5782-2 · Cited by 98 · see citing works
Exploiting genomics to mitigate the public health impact of antimicrobial resistance
Waddington, C. S., Carey, M. E., Boinett, C. J., Higginson, E. E., Veeraraghavan, B., & Baker, S. G. (2022) · Genome Medicine · doi:10.1186/s13073-022-01020-2 · Cited by 97 · see citing works
Dookie, N., Ngema, S. L., Perumal, R., Naicker, N., Padayatchi, N., & Naidoo, K. (2022) · Clinical Microbiology Reviews · doi:10.1128/cmr.00180-19 · Cited by 97 · see citing works
Drug-Resistant Tuberculosis 2020: Where We Stand
Iacobino, A., Fattorini, L., & Giannoni, F. (2020) · Applied Sciences · doi:10.3390/app10062153 · Cited by 69 · see citing works
Green, A. G., Yoon, C. H., Chen, M. L., Ektefaie, Y., Fina, M., Freschi, L., Gröschel, M. I., Kohane, I. S., Beam, A. L., & Farhat, M. R. (2022) · Nature Communications · doi:10.1038/s41467-022-31236-0 · Cited by 90 · see citing works
Hall, M. B., Rabodoarivelo, M. S., Koch, A. S., Dippenaar, A., George, S. A., Grobbelaar, M., Warren, R. M., Walker, T. M., Cox, H. S., Gagneux, S., et al. (2022) · The Lancet Microbe · doi:10.1016/s2666-5247(22)00301-9 · Cited by 89 · see citing works
Integrating Pharmacokinetics and Pharmacodynamics in Operational Research to End Tuberculosis
Alffenaar, J. C., Gumbo, T., Dooley, K. E., Peloquin, C. A., McIlleron, H., Zagorski, A., Cirillo, D. M., Heysell, S. K., Silva, D. R., & Migliori, G. B. (2019) · Clinical Infectious Diseases · doi:10.1093/cid/ciz942 · Cited by 88 · see citing works
Dynamics of within-host Mycobacterium tuberculosis diversity and heteroresistance during treatment
Nimmo, C., Brien, K., Millard, J., Grant, A. D., Padayatchi, N., Pym, A. S., O’Donnell, M. R., Goldstein, R. A., Breuer, J., & Balloux, F. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102747 · Cited by 87 · see citing works
Liu, D., Huang, F., Zhang, G., He, W., Ou, X., He, P., Zhao, B. T., Zhu, B., Liu, F., Li, Z., et al. (2021) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2021.09.014 · Cited by 87 · see citing works
Point-of-care diagnostic tests for tuberculosis disease
Hóng, J., Lee, H., Menon, N. V., Lim, C. T., Lee, L. P., & Ong, C. W. M. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abj4124 · Cited by 86 · see citing works
de la Lastra, J. M. P., Wardell, S. J. T., Pal, T., de la Fuente‐Núñez, C., & Pletzer, D. (2024) · Journal of Medical Systems · doi:10.1007/s10916-024-02089-5 · Cited by 92 · see citing works
Management of patients with multidrug-resistant tuberculosis
Lange, C. G., Aarnoutse, R. E., Alffenaar, J. W. C., Bothamley, G. H., Brinkmann, F., Costa, J. P., Chesov, D., van Crevel, R., Dedicoat, M. J., Domínguez, J., et al. (2019) · The International Journal of Tuberculosis and Lung Disease · doi:10.5588/ijtld.18.0622 · Cited by 86 · see citing works
Kim, J., Greenberg, D. E., Pifer, R., Jiang, S., Xiao, G., Shelburne, S. A., Koh, A. Y., Xie, Y., & Zhan, X. (2020) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1007511 · Cited by 86 · see citing works
Whole-Genome Sequencing for Drug Resistance Profile Prediction in Mycobacterium tuberculosis
Gygli, S. M., Keller, P. M., Ballif, M., Blöchliger, N., Hömke, R., Reinhard, M., Loiseau, C., Ritter, C., Sander, P., Borrell, S., et al. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02175-18 · Cited by 86 · see citing works
Fowler, P. W., Barilar, I., Battaglia, S., Borroni, E., Brandao, A. P., Brankin, A., Cabibbe, A. M., Carter, J. J., Cirillo, D. M., Claxton, P., et al. (2022) · European Respiratory Journal · doi:10.1183/13993003.00239-2022 · Cited by 84 · see citing works
Drug-resistance in Mycobacterium tuberculosis : where we stand
Mabhula, A., & Singh, V. (2019) · MedChemComm · doi:10.1039/c9md00057g · Cited by 84 · see citing works
Merker, M., Kohl, T. A., Barilar, I., Andres, S., Fowler, P. W., Chryssanthou, E., Ängeby, K., Juréen, P., Moradigaravand, D., Parkhill, J., et al. (2020) · Genome Medicine · doi:10.1186/s13073-020-00726-5 · Cited by 83 · see citing works
The Cryptic Consortium (2022) · PLoS Biology · doi:10.1371/journal.pbio.3001755 · Cited by 83 · see citing works
Gröschel, M. I., Owens, M., Freschi, L., Vargas, R., Marin, M. G., Phelan, J. E., Iqbal, Z., Dixit, A., & Farhat, M. R. (2021) · Genome Medicine · doi:10.1186/s13073-021-00953-4 · Cited by 81 · see citing works
Kuang, X., Wang, F., Hernandez, K. M., Zhang, Z., & Grossman, R. L. (2022) · Scientific Reports · doi:10.1038/s41598-022-06449-4 · Cited by 82 · see citing works
Advancing pathogen genomics in resource-limited settings
Pronyk, P., de Alwis, R., Rockett, R. J., Basile, K., Boucher, Y., Pang, V., Sessions, O. M., Getchell, M., Golubchik, T., Lam, C., et al. (2023) · Cell Genomics · doi:10.1016/j.xgen.2023.100443 · Cited by 82 · see citing works
Colman, R. E., Macé, A., Seifert, M., Hetzel, J., Mshaiel, H., Suresh, A., Lemmer, D., Engelthaler, D. M., Catanzaro, D. G., Young, A. G., et al. (2019) · PLoS Medicine · doi:10.1371/journal.pmed.1002794 · Cited by 79 · see citing works
Role and value of whole genome sequencing in studying tuberculosis transmission
Nikolayevskyy, V., Niemann, S., Anthony, R. M., van Soolingen, D., Tagliani, E., Ködmön, C., van der Werf, M. J., & Cirillo, D. M. (2019) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2019.03.022 · Cited by 79 · see citing works
Goig, G. A., Cancino‐Muñoz, I., Torres‐Puente, M., Villamayor, L. M., Navarro, D., Borrás, R., & Comas, I. (2020) · The Lancet Microbe · doi:10.1016/s2666-5247(20)30060-4 · Cited by 78 · see citing works
Oxford nanopore sequencing in clinical microbiology and infection diagnostics
Sheka, D., Alabi, N., & Gordon, P. M. K. (2020) · Briefings in Bioinformatics · doi:10.1093/bib/bbaa403 · Cited by 76 · see citing works
Maximum likelihood pandemic-scale phylogenetics
Maio, N. D., Kalaghatgi, P., Turakhia, Y., Corbett-Detig, R. B., Minh, B. Q., & Goldman, N. (2023) · Nature Genetics · doi:10.1038/s41588-023-01368-0 · Cited by 72 · see citing works
Current and future treatments for tuberculosis
Lee, A. J., Xie, Y. L., Barry, C. E., & Chen, R. Y. (2020) · BMJ · doi:10.1136/bmj.m216 · Cited by 72 · see citing works
Perspective for Precision Medicine for Tuberculosis
Lange, C. G., Aarnoutse, R. E., Chesov, D., van Crevel, R., Gillespie, S. H., Grobbel, H.-P., Kalsdorf, B., Kontsevaya, I., van Laarhoven, A., Nishiguchi, T., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.566608 · Cited by 71 · see citing works
Structure guided prediction of Pyrazinamide resistance mutations in pncA
Karmakar, M., Rodrigues, C. H. M., Horan, K., Denholm, J. T., & Ascher, D. B. (2020) · Scientific Reports · doi:10.1038/s41598-020-58635-x · Cited by 71 · see citing works
Tagliani, E., Anthony, R. M., Kohl, T. A., de Neeling, A. J., Nikolayevskyy, V., Ködmön, C., Maurer, F. P., Niemann, S., van Soolingen, D., van der Werf, M. J., et al. (2020) · European Respiratory Journal · doi:10.1183/13993003.02272-2020 · Cited by 70 · see citing works
Dookie, N., Khan, A., Padayatchi, N., & Naidoo, K. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.775030 · Cited by 68 · see citing works
Genomic signatures of pre-resistance in Mycobacterium tuberculosis
Ortiz, A. T., Coronel, J., Vidal, J. R., Bonilla-Asalde, C. A., Moore, D., Gilman, R. H., Balloux, F., Kon, O. M., Didelot, X., & Grandjean, L. (2021) · Nature Communications · doi:10.1038/s41467-021-27616-7 · Cited by 66 · see citing works
An African origin for Mycobacterium bovis
Loiseau, C., Menardo, F., Aseffa, A., Hailu, E., Gumi, B., Ameni, G., Berg, S., Rigouts, L., Robbe‐Austerman, S., Zinsstag, J., et al. (2020) · Evolution Medicine and Public Health · doi:10.1093/emph/eoaa005 · Cited by 61 · see citing works
Yang, T., Gan, M., Liu, Q., Liang, W., Tang, Q., Luo, G., Zuo, T., Guo, Y., Hong, C., Li, Q., et al. (2022) · Briefings in Bioinformatics · doi:10.1093/bib/bbac030 · Cited by 64 · see citing works
An accessible, efficient and global approach for the large-scale sequencing of bacterial genomes
Perez-Sepulveda, B. M., Heavens, D., Pulford, C. V., Predeus, A. V., Low, R. S., Webster, H. J., Dykes, G. F., Schudoma, C., Rowe, W. P. M., Lipscombe, J., et al. (2021) · Genome biology · doi:10.1186/s13059-021-02536-3 · Cited by 64 · see citing works
Cryo-EM structure and resistance landscape of M. tuberculosis MmpL3: An emergent therapeutic target
Adams, O., Deme, J. C., Parker, J. L., Fowler, P. W., Lea, S. M., & Newstead, S. (2021) · Structure · doi:10.1016/j.str.2021.06.013 · Cited by 63 · see citing works
Pataki, B., Matamoros, S., van der Putten, B. C. L., Remondini, D., Giampieri, E., Aytan-Aktug, D., Hendriksen, R. S., Lund, O., Csabai, I., Schultsz, C., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-71693-5 · Cited by 62 · see citing works
Bioinformatics Approaches to the Understanding of Molecular Mechanisms in Antimicrobial Resistance
Camp, P.-J. V., Haslam, D. B., & Porollo, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041363 · Cited by 62 · see citing works
Jajou, R., Kohl, T. A., Walker, T., Norman, A., Cirillo, D. M., Tagliani, E., Niemann, S., de Neeling, A. J., Lillebæk, T., Anthony, R. M., et al. (2019) · Eurosurveillance · doi:10.2807/1560-7917.es.2019.24.50.1900130 · Cited by 61 · see citing works
Role of Artificial Intelligence in Fighting Antimicrobial Resistance in Pediatrics
Fanelli, U., Pappalardo, M., Chiné, V., Gismondi, P., Neglia, C., Argentiero, A., Calderaro, A., Prati, A., & Esposito, S. (2020) · Antibiotics · doi:10.3390/antibiotics9110767 · Cited by 61 · see citing works
Foudraine, D. E., Strepis, N., Stingl, C., ten Kate, M. T., Verbon, A., Klaassen, C. H. W., Goessens, W. H. F., Luider, T. M., & Dekker, L. J. M. (2021) · Scientific Reports · doi:10.1038/s41598-021-91905-w · Cited by 60 · see citing works
Ektefaie, Y., Dixit, A., Freschi, L., & Farhat, M. R. (2021) · The Lancet Microbe · doi:10.1016/s2666-5247(20)30195-6 · Cited by 57 · see citing works
Zwyer, M., Çavuşoğlu, C., Ghielmetti, G., Pacciarini, M. L., Scaltriti, E., van Soolingen, D., Doetsch, A., Reinhard, M., Gagneux, S., & Brites, D. (2021) · Open Research Europe · doi:10.12688/openreseurope.14029.2 · Cited by 56 · see citing works
Barilar, I., Battaglia, S., Borroni, E., Brandão, A. P., Brankin, A. E., Cabibbe, A. M., Carter, J. J., Chetty, D., Cirillo, D. M., Claxton, P., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-44325-5 · Cited by 56 · see citing works
Pathogen-based precision medicine for drug-resistant tuberculosis
Gröschel, M. I., Walker, T. M., van der Werf, T. S., Lange, C. G., Niemann, S., & Merker, M. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1007297 · Cited by 55 · see citing works
Infection prevention and control insights from a decade of pathogen whole-genome sequencing
Eyre, D. W. (2022) · Journal of Hospital Infection · doi:10.1016/j.jhin.2022.01.024 · Cited by 54 · see citing works
Kambli, P., Ajbani, K., Kazi, M. I., Sadani, M., Naik, S., Shetty, A., Tornheim, J. A., Singh, H., & Rodrigues, C. S. (2021) · Tuberculosis · doi:10.1016/j.tube.2021.102051 · Cited by 54 · see citing works
Value of routine whole genome sequencing for Mycobacterium tuberculosis drug resistance detection
Lam, C., Martinez, E. M., Crighton, T., Furlong, C., Donnan, E., Marais, B. J., & Sintchenko, V. (2021) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2021.03.033 · Cited by 54 · see citing works
The Potential Role of Clinical Metagenomics in Infectious Diseases: Therapeutic Perspectives
d’Humières, C., Salmona, M., Dellière, S., Léo, S., Rodriguez, C., Angebault, C., Alanio, A., Fourati, S., Lazarević, V., Woerther, P., et al. (2021) · Drugs · doi:10.1007/s40265-021-01572-4 · Cited by 53 · see citing works
Distinct Bacterial Pathways Influence the Efficacy of Antibiotics against Mycobacterium tuberculosis
Bellerose, M. M., Proulx, M. K., Smith, C. M., Baker, R. E., Ioerger, T., & Sassetti, C. (2020) · mSystems · doi:10.1128/msystems.00396-20 · Cited by 48 · see citing works
Mycobacterium tuberculosis Next-Generation Whole Genome Sequencing: Opportunities and Challenges
Iketleng, T., Lessells, R. J., Dlamini, M. T., Mogashoa, T., Mupfumi, L., Moyo, S. M., Gaseitsiwe, S., & de Oliveira, T. (2018) · Tuberculosis Research and Treatment · doi:10.1155/2018/1298542 · Cited by 52 · see citing works
Assessing evolutionary risks of resistance for new antimicrobial therapies
Brockhurst, M. A., Harrison, F., Veening, J., Harrison, E., Blackwell, G. A., Iqbal, Z., & MacLean, R. C. (2019) · Nature Ecology & Evolution · doi:10.1038/s41559-019-0854-x · Cited by 50 · see citing works
Katale, B. Z., Mbelele, P. M., Lema, N. A., Campino, S. G., Mshana, S. E., Rweyemamu, M. M., Phelan, J. E., Keyyu, J. D., Majigo, M. V., Mbugi, E. V., et al. (2020) · BMC Genomics · doi:10.1186/s12864-020-6577-1 · Cited by 52 · see citing works
Tuberculosis Genetic Epidemiology: A Latin American Perspective
Woodman, M., Haeusler, I. L., & Grandjean, L. (2019) · Genes · doi:10.3390/genes10010053 · Cited by 51 · see citing works
Epperson, L. E., & Strong, M. (2020) · Journal of Clinical Tuberculosis and Other Mycobacterial Diseases · doi:10.1016/j.jctube.2020.100150 · Cited by 50 · see citing works
Gene evolutionary trajectories in Mycobacterium tuberculosis reveal temporal signs of selection
Chiner‐Oms, Á., López, M. G., Moreno-Molina, M., Furió, V., & Comas, I. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2113600119 · Cited by 48 · see citing works
Finci, I., Albertini, A., Merker, M., Andres, S., Bablishvili, N., Barilar, I., Cáceres, T., Crudu, V., Gotuzzo, E., Hapeela, N., et al. (2022) · The Lancet Microbe · doi:10.1016/s2666-5247(22)00116-1 · Cited by 48 · see citing works
Diagnosis and biomarkers for ocular tuberculosis: From the present into the future
Ludi, Z., Sule, A. A., Samy, R. P., Putera, I., Schrijver, B., Hutchinson, P. E., Gunaratne, J., Verma, I., Singhal, A., Nora, R. L. D., et al. (2023) · Theranostics · doi:10.7150/thno.81488 · Cited by 52 · see citing works
Genestet, C., Hodille, E., Berland, J., Ginévra, C., Bryant, J. E., Ader, F., Lina, G., & Dumitrescu, O. (2020) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2020.105912 · Cited by 48 · see citing works
- Authors
- The CRyPTIC Consortium and the 100, 0. G. P.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-10-11
- Volume
- 379
- Issue
- 15
- Pages
- 1403-1415
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC6121966
- OpenAlex
- W2902271181
- Cited by
- 500
- References
- 22
- Citations by year
- 2026: 25 · 2025: 41 · 2024: 58 · 2023: 61 · 2022: 78 · 2021: 65 · 2020: 89 · 2019: 72 · 2018: 9 · 2017: 1
- FWCI
- 44.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- New England Journal of Medicine (publishedVersion, cc-by)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by)
- PubMed Central (acceptedVersion, cc-by)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- HAL (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Florence Research (University of Florence) (submittedVersion)
- LillOA (Université de Lille (University Of Lille)) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Seventh Framework Programme (278864)
- European Research Council (638553-TB-ACCELERATE)
- Wellcome Trust and the Royal Society Sir Henry Dale Fellowships (101237/Z/13/Z, 102541/A/13/Z)
- National University of Singapore Yong Loo Lin School of Medicine Aspiration Fund (NUHSRO/2014/069/AF-New Idea/04)
- Ministerio de Economía y Competitividad (SAF2016-77346-R)
- National Science and Technology Key Program of China (2014ZX10003002)
- National Basic Research program of China (2014CB744403)
- Health Services and Delivery Research Programme
- Bill and Melinda Gates Foundation (OPP1133541)
- Wellcome Trust (200205/Z/15/Z)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Keywords
- Mycobacterium tuberculosis complex, first-line antituberculosis drugs, isoniazid resistance, rifampicin resistance, ethambutol resistance, pyrazinamide resistance, drug resistance mutations, whole genome sequencing, genotype-phenotype correlation, negative predictive value
- MeSH terms
- Whole Genome Sequencing, Antitubercular Agents, Ethambutol, Genotype, Humans, Isoniazid, Microbial Sensitivity Tests, Mutation, Mycobacterium tuberculosis, Phenotype, Pyrazinamide, Rifampin, Tuberculosis, Genome, Bacterial, Drug Resistance, Bacterial
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