Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach
The World Health Organization has a goal of universal drug susceptibility testing for patients with tuberculosis; however, molecular diagnostics to date have focused largely on first-line drugs and predicting binary susceptibilities. We used a multivariable linear mixed model alongside whole genome...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| 其他作者: | |
| 格式: | Journal article |
| 語言: | English |
| 出版: |
Springer Nature
2024
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| _version_ | 1826312248103010304 |
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| author | Barilar, I Battaglia, S Borroni, E Zankin, A Clifton, D Crook, D Earle, S Fowler, PW Giberto Cruz, A Hoosdally, S Knaggs, J Hunt, M Kouchaki, S Lachapelle, A Peto, T Rodger, G Roohi, A Thwaites, G Walker, AS Wilson, D Yang, Y |
| author2 | Cryptic Consortium |
| author_facet | Cryptic Consortium Barilar, I Battaglia, S Borroni, E Zankin, A Clifton, D Crook, D Earle, S Fowler, PW Giberto Cruz, A Hoosdally, S Knaggs, J Hunt, M Kouchaki, S Lachapelle, A Peto, T Rodger, G Roohi, A Thwaites, G Walker, AS Wilson, D Yang, Y |
| author_sort | Barilar, I |
| collection | OXFORD |
| description | The World Health Organization has a goal of universal drug susceptibility testing for
patients with tuberculosis; however, molecular diagnostics to date have focused largely
on first-line drugs and predicting binary susceptibilities. We used a multivariable linear
mixed model alongside whole genome sequencing and a quantitative microtiter plate
assay to relate genomic mutations to minimum inhibitory concentration in 15,211
Mycobacterium tuberculosis patient isolates from 23 countries across five continents.
This identified 492 unique MIC-elevating variants across thirteen drugs, as well as 91
mutations resulting in hypersensitivity. Our results advance genetics-based diagnostics
for tuberculosis and serve as a curated training/testing dataset for development of drug
resistance prediction algorithms. |
| first_indexed | 2024-03-07T08:26:15Z |
| format | Journal article |
| id | oxford-uuid:77be4739-88b3-4f3f-a83b-8c6c9b1ac44e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:26:15Z |
| publishDate | 2024 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:77be4739-88b3-4f3f-a83b-8c6c9b1ac44e2024-02-15T09:29:41ZQuantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approachJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:77be4739-88b3-4f3f-a83b-8c6c9b1ac44eEnglishSymplectic ElementsSpringer Nature2024Barilar, IBattaglia, SBorroni, EZankin, AClifton, DCrook, DEarle, SFowler, PWGiberto Cruz, AHoosdally, SKnaggs, JHunt, MKouchaki, SLachapelle, APeto, TRodger, GRoohi, AThwaites, GWalker, ASWilson, DYang, YCryptic ConsortiumThe World Health Organization has a goal of universal drug susceptibility testing for patients with tuberculosis; however, molecular diagnostics to date have focused largely on first-line drugs and predicting binary susceptibilities. We used a multivariable linear mixed model alongside whole genome sequencing and a quantitative microtiter plate assay to relate genomic mutations to minimum inhibitory concentration in 15,211 Mycobacterium tuberculosis patient isolates from 23 countries across five continents. This identified 492 unique MIC-elevating variants across thirteen drugs, as well as 91 mutations resulting in hypersensitivity. Our results advance genetics-based diagnostics for tuberculosis and serve as a curated training/testing dataset for development of drug resistance prediction algorithms. |
| spellingShingle | Barilar, I Battaglia, S Borroni, E Zankin, A Clifton, D Crook, D Earle, S Fowler, PW Giberto Cruz, A Hoosdally, S Knaggs, J Hunt, M Kouchaki, S Lachapelle, A Peto, T Rodger, G Roohi, A Thwaites, G Walker, AS Wilson, D Yang, Y Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach |
| title | Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach |
| title_full | Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach |
| title_fullStr | Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach |
| title_full_unstemmed | Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach |
| title_short | Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach |
| title_sort | quantitative measurement of antibiotic resistance in mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach |
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