Quantitative measurement of antibiotic resistance in <i>Mycobacterium tuberculosis</i> reveals genetic determinants of resistance and susceptibility in a target gene approach. Barilar, I., Battaglia, S., Borroni, E., Brandao, A. P., Brankin, A., Cabibbe, A. M., Carter, J., Chetty, D., Cirillo, D. M., Claxton, P., Clifton, D. A, Cohen, T., Coronel, J., Crook, D. W, Dreyer, V., Earle, S. G., Escuyer, V., Ferrazoli, L., Fowler, P. W, Gao, G. F., Gardy, J., Gharbia, S., Ghisi, K. T., Ghodousi, A., Gibertoni Cruz, A. L., Grandjean, L., Grazian, C., Groenheit, R., Guthrie, J. L, He, W., Hoffmann, H., Hoosdally, S. J, Hunt, M., Iqbal, Z., Ismail, N. A., Jarrett, L., Joseph, L., Jou, R., Kambli, P., Khot, R., Knaggs, J., Koch, A., Kohlerschmidt, D., Kouchaki, S., Lachapelle, A. S, Lalvani, A., Lapierre, S. G., Laurenson, I. F, Letcher, B., Lin, W., Liu, C., Liu, D., Malone, K. M, Mandal, A., Mansjö, M., Calisto Matias, D. V. L., Meintjes, G. A, de Freitas Mendes , F., Merker, M., Mihalic, M., Millard, J., Miotto, P., Mistry, N., Moore, D., Musser, K. A, Ngcamu, D., Nhung, H. N., Niemann, S., Nilgiriwala, K. S., Nimmo, C., O'Donnell, M., Okozi, N., Oliveira, R. S., Omar, S. V., Paton, N., Peto, T. E A, Pinhata, J. M. W., Plesnik, S., Puyen, Z. M, Rabodoarivelo, M. S., Rakotosamimanana, N., Rancoita, P. M V, Rathod, P., Robinson, E. R., Rodger, G., Rodrigues, C., Rodwell, T. C, Roohi, A., Santos-Lazaro, D., Shah, S., Smith, G., Kohl, T. A., Solano, W., Spitaleri, A., Steyn, A. J C, Supply, P., Surve, U., Tahseen, S., Thuong, N. T. T., Thwaites, G., Todt, K., Trovato, A., Utpatel, C., Van Rie, A., Vijay, S., Walker, A S., Walker, T. M, Warren, R., Werngren, J., Wijkander, M., Wilkinson, R. J, Wilson, D. J, Wintringer, P., Xiao, Y., Yang, Y., Yanlin, Z., Yao, S., & Zhu, B. Nature Communications, 15(1):488, Nature Publishing Group, jan, 2024. ![Quantitative measurement of antibiotic resistance in <i>Mycobacterium tuberculosis</i> reveals genetic determinants of resistance and susceptibility in a target gene approach [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 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 susceptibilities in a binary manner (classifying strains as either susceptible or resistant). Here, 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 (MIC) in 15,211 Mycobacterium tuberculosis clinical isolates from 23 countries across five continents. We identified 492 unique MIC-elevating variants across 13 drugs, as well as 91 mutations likely linked to hypersensitivity. Our results advance genetics-based diagnostics for tuberculosis and serve as a curated training/testing dataset for development of drug resistance prediction algorithms. Molecular diagnostics for tuberculosis have focused on predicting drug susceptibilities in a binary manner (i.e., strains are either susceptible or resistant). Here, CRyPTIC Consortium researchers use whole genome sequencing and a quantitative assay to identify associations between genomic mutations and minimum inhibitory concentrations in over 15,000 Mycobacterium tuberculosis clinical isolates.
@article{Barilar2024,
abstract = {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 susceptibilities in a binary manner (classifying strains as either susceptible or resistant). Here, 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 (MIC) in 15,211 Mycobacterium tuberculosis clinical isolates from 23 countries across five continents. We identified 492 unique MIC-elevating variants across 13 drugs, as well as 91 mutations likely linked to hypersensitivity. Our results advance genetics-based diagnostics for tuberculosis and serve as a curated training/testing dataset for development of drug resistance prediction algorithms. Molecular diagnostics for tuberculosis have focused on predicting drug susceptibilities in a binary manner (i.e., strains are either susceptible or resistant). Here, CRyPTIC Consortium researchers use whole genome sequencing and a quantitative assay to identify associations between genomic mutations and minimum inhibitory concentrations in over 15,000 Mycobacterium tuberculosis clinical isolates.},
author = {Barilar, Ivan and Battaglia, Simone and Borroni, Emanuele and Brandao, Angela Pires and Brankin, Alice and Cabibbe, Andrea Maurizio and Carter, Joshua and Chetty, Darren and Cirillo, Daniela Maria and Claxton, Pauline and Clifton, David A and Cohen, Ted and Coronel, Jorge and Crook, Derrick W and Dreyer, Viola and Earle, Sarah G. and Escuyer, Vincent and Ferrazoli, Lucilaine and Fowler, Philip W and Gao, George Fu and Gardy, Jennifer and Gharbia, Saheer and Ghisi, Kelen Teixeira and Ghodousi, Arash and {Gibertoni Cruz}, Ana Lu{\'{i}}za and Grandjean, Louis and Grazian, Clara and Groenheit, Ramona and Guthrie, Jennifer L and He, Wencong and Hoffmann, Harald and Hoosdally, Sarah J and Hunt, Martin and Iqbal, Zamin and Ismail, Nazir Ahmed and Jarrett, Lisa and Joseph, Lavania and Jou, Ruwen and Kambli, Priti and Khot, Rukhsar and Knaggs, Jeff and Koch, Anastasia and Kohlerschmidt, Donna and Kouchaki, Samaneh and Lachapelle, Alexander S and Lalvani, Ajit and Lapierre, Simon Grandjean and Laurenson, Ian F and Letcher, Brice and Lin, Wan-Hsuan and Liu, Chunfa and Liu, Dongxin and Malone, Kerri M and Mandal, Ayan and Mansj{\"{o}}, Mikael and {Calisto Matias}, Daniela Vicente Lucena and Meintjes, Graeme A and {de Freitas Mendes}, Fl{\'{a}}via and Merker, Matthias and Mihalic, Marina and Millard, James and Miotto, Paolo and Mistry, Nerges and Moore, David and Musser, Kimberlee A and Ngcamu, Dumisani and Nhung, Hoang Ngoc and Niemann, Stefan and Nilgiriwala, Kayzad Soli and Nimmo, Camus and O'Donnell, Max and Okozi, Nana and Oliveira, Rosangela Siqueira and Omar, Shaheed Vally and Paton, Nicholas and Peto, Timothy E A and Pinhata, Juliana Maira Watanabe and Plesnik, Sara and Puyen, Zully M and Rabodoarivelo, Marie Sylvianne and Rakotosamimanana, Niaina and Rancoita, Paola M V and Rathod, Priti and Robinson, Esther Rhiannon and Rodger, Gillian and Rodrigues, Camilla and Rodwell, Timothy C and Roohi, Aysha and Santos-Lazaro, David and Shah, Sanchi and Smith, Grace and Kohl, Thomas Andreas and Solano, Walter and Spitaleri, Andrea and Steyn, Adrie J C and Supply, Philip and Surve, Utkarsha and Tahseen, Sabira and Thuong, Nguyen Thuy Thuong and Thwaites, Guy and Todt, Katharina and Trovato, Alberto and Utpatel, Christian and {Van Rie}, Annelies and Vijay, Srinivasan and Walker, A Sarah and Walker, Timothy M and Warren, Robin and Werngren, Jim and Wijkander, Maria and Wilkinson, Robert J and Wilson, Daniel J and Wintringer, Penelope and Xiao, Yu-Xin and Yang, Yang and Yanlin, Zhao and Yao, Shen-Yuan and Zhu, Baoli},
doi = {10.1038/s41467-023-44325-5},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Barilar et al. - 2024 - Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of.pdf:pdf},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {Antibiotics,Antimicrobial resistance,Bacterial genes,Infectious,OA,OA{\_}PMC,Pathogens,disease diagnostics,fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,original},
month = {jan},
number = {1},
pages = {488},
pmid = {38216576},
publisher = {Nature Publishing Group},
title = {{Quantitative measurement of antibiotic resistance in \textit{Mycobacterium tuberculosis} reveals genetic determinants of resistance and susceptibility in a target gene approach}},
url = {https://www.nature.com/articles/s41467-023-44325-5},
volume = {15},
year = {2024}
}
Downloads: 0
{"_id":"GSBAD6HjEq234dcT3","bibbaseid":"barilar-battaglia-borroni-brandao-brankin-cabibbe-carter-chetty-etal-quantitativemeasurementofantibioticresistanceinimycobacteriumtuberculosisirevealsgeneticdeterminantsofresistanceandsusceptibilityinatargetgeneapproach-2024","author_short":["Barilar, I.","Battaglia, S.","Borroni, E.","Brandao, A. P.","Brankin, A.","Cabibbe, A. M.","Carter, J.","Chetty, D.","Cirillo, D. M.","Claxton, P.","Clifton, D. A","Cohen, T.","Coronel, J.","Crook, D. W","Dreyer, V.","Earle, S. G.","Escuyer, V.","Ferrazoli, L.","Fowler, P. W","Gao, G. F.","Gardy, J.","Gharbia, S.","Ghisi, K. T.","Ghodousi, A.","Gibertoni Cruz, A. L.","Grandjean, L.","Grazian, C.","Groenheit, R.","Guthrie, J. L","He, W.","Hoffmann, H.","Hoosdally, S. J","Hunt, M.","Iqbal, Z.","Ismail, N. A.","Jarrett, L.","Joseph, L.","Jou, R.","Kambli, P.","Khot, R.","Knaggs, J.","Koch, A.","Kohlerschmidt, D.","Kouchaki, S.","Lachapelle, A. S","Lalvani, A.","Lapierre, S. G.","Laurenson, I. F","Letcher, B.","Lin, W.","Liu, C.","Liu, D.","Malone, K. M","Mandal, A.","Mansjö, M.","Calisto Matias, D. V. L.","Meintjes, G. A","de Freitas Mendes , F.","Merker, M.","Mihalic, M.","Millard, J.","Miotto, P.","Mistry, N.","Moore, D.","Musser, K. A","Ngcamu, D.","Nhung, H. N.","Niemann, S.","Nilgiriwala, K. S.","Nimmo, C.","O'Donnell, M.","Okozi, N.","Oliveira, R. S.","Omar, S. V.","Paton, N.","Peto, T. E A","Pinhata, J. M. W.","Plesnik, S.","Puyen, Z. M","Rabodoarivelo, M. S.","Rakotosamimanana, N.","Rancoita, P. M V","Rathod, P.","Robinson, E. R.","Rodger, G.","Rodrigues, C.","Rodwell, T. C","Roohi, A.","Santos-Lazaro, D.","Shah, S.","Smith, G.","Kohl, T. A.","Solano, W.","Spitaleri, A.","Steyn, A. J C","Supply, P.","Surve, U.","Tahseen, S.","Thuong, N. T. T.","Thwaites, G.","Todt, K.","Trovato, A.","Utpatel, C.","Van Rie, A.","Vijay, S.","Walker, A S.","Walker, T. M","Warren, R.","Werngren, J.","Wijkander, M.","Wilkinson, R. J","Wilson, D. J","Wintringer, P.","Xiao, Y.","Yang, Y.","Yanlin, Z.","Yao, S.","Zhu, B."],"bibdata":{"bibtype":"article","type":"article","abstract":"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 susceptibilities in a binary manner (classifying strains as either susceptible or resistant). Here, 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 (MIC) in 15,211 Mycobacterium tuberculosis clinical isolates from 23 countries across five continents. We identified 492 unique MIC-elevating variants across 13 drugs, as well as 91 mutations likely linked to hypersensitivity. Our results advance genetics-based diagnostics for tuberculosis and serve as a curated training/testing dataset for development of drug resistance prediction algorithms. Molecular diagnostics for tuberculosis have focused on predicting drug susceptibilities in a binary manner (i.e., strains are either susceptible or resistant). Here, CRyPTIC Consortium researchers use whole genome sequencing and a quantitative assay to identify associations between genomic mutations and minimum inhibitory concentrations in over 15,000 Mycobacterium tuberculosis clinical isolates.","author":[{"propositions":[],"lastnames":["Barilar"],"firstnames":["Ivan"],"suffixes":[]},{"propositions":[],"lastnames":["Battaglia"],"firstnames":["Simone"],"suffixes":[]},{"propositions":[],"lastnames":["Borroni"],"firstnames":["Emanuele"],"suffixes":[]},{"propositions":[],"lastnames":["Brandao"],"firstnames":["Angela","Pires"],"suffixes":[]},{"propositions":[],"lastnames":["Brankin"],"firstnames":["Alice"],"suffixes":[]},{"propositions":[],"lastnames":["Cabibbe"],"firstnames":["Andrea","Maurizio"],"suffixes":[]},{"propositions":[],"lastnames":["Carter"],"firstnames":["Joshua"],"suffixes":[]},{"propositions":[],"lastnames":["Chetty"],"firstnames":["Darren"],"suffixes":[]},{"propositions":[],"lastnames":["Cirillo"],"firstnames":["Daniela","Maria"],"suffixes":[]},{"propositions":[],"lastnames":["Claxton"],"firstnames":["Pauline"],"suffixes":[]},{"propositions":[],"lastnames":["Clifton"],"firstnames":["David","A"],"suffixes":[]},{"propositions":[],"lastnames":["Cohen"],"firstnames":["Ted"],"suffixes":[]},{"propositions":[],"lastnames":["Coronel"],"firstnames":["Jorge"],"suffixes":[]},{"propositions":[],"lastnames":["Crook"],"firstnames":["Derrick","W"],"suffixes":[]},{"propositions":[],"lastnames":["Dreyer"],"firstnames":["Viola"],"suffixes":[]},{"propositions":[],"lastnames":["Earle"],"firstnames":["Sarah","G."],"suffixes":[]},{"propositions":[],"lastnames":["Escuyer"],"firstnames":["Vincent"],"suffixes":[]},{"propositions":[],"lastnames":["Ferrazoli"],"firstnames":["Lucilaine"],"suffixes":[]},{"propositions":[],"lastnames":["Fowler"],"firstnames":["Philip","W"],"suffixes":[]},{"propositions":[],"lastnames":["Gao"],"firstnames":["George","Fu"],"suffixes":[]},{"propositions":[],"lastnames":["Gardy"],"firstnames":["Jennifer"],"suffixes":[]},{"propositions":[],"lastnames":["Gharbia"],"firstnames":["Saheer"],"suffixes":[]},{"propositions":[],"lastnames":["Ghisi"],"firstnames":["Kelen","Teixeira"],"suffixes":[]},{"propositions":[],"lastnames":["Ghodousi"],"firstnames":["Arash"],"suffixes":[]},{"propositions":[],"lastnames":["Gibertoni Cruz"],"firstnames":["Ana","Luíza"],"suffixes":[]},{"propositions":[],"lastnames":["Grandjean"],"firstnames":["Louis"],"suffixes":[]},{"propositions":[],"lastnames":["Grazian"],"firstnames":["Clara"],"suffixes":[]},{"propositions":[],"lastnames":["Groenheit"],"firstnames":["Ramona"],"suffixes":[]},{"propositions":[],"lastnames":["Guthrie"],"firstnames":["Jennifer","L"],"suffixes":[]},{"propositions":[],"lastnames":["He"],"firstnames":["Wencong"],"suffixes":[]},{"propositions":[],"lastnames":["Hoffmann"],"firstnames":["Harald"],"suffixes":[]},{"propositions":[],"lastnames":["Hoosdally"],"firstnames":["Sarah","J"],"suffixes":[]},{"propositions":[],"lastnames":["Hunt"],"firstnames":["Martin"],"suffixes":[]},{"propositions":[],"lastnames":["Iqbal"],"firstnames":["Zamin"],"suffixes":[]},{"propositions":[],"lastnames":["Ismail"],"firstnames":["Nazir","Ahmed"],"suffixes":[]},{"propositions":[],"lastnames":["Jarrett"],"firstnames":["Lisa"],"suffixes":[]},{"propositions":[],"lastnames":["Joseph"],"firstnames":["Lavania"],"suffixes":[]},{"propositions":[],"lastnames":["Jou"],"firstnames":["Ruwen"],"suffixes":[]},{"propositions":[],"lastnames":["Kambli"],"firstnames":["Priti"],"suffixes":[]},{"propositions":[],"lastnames":["Khot"],"firstnames":["Rukhsar"],"suffixes":[]},{"propositions":[],"lastnames":["Knaggs"],"firstnames":["Jeff"],"suffixes":[]},{"propositions":[],"lastnames":["Koch"],"firstnames":["Anastasia"],"suffixes":[]},{"propositions":[],"lastnames":["Kohlerschmidt"],"firstnames":["Donna"],"suffixes":[]},{"propositions":[],"lastnames":["Kouchaki"],"firstnames":["Samaneh"],"suffixes":[]},{"propositions":[],"lastnames":["Lachapelle"],"firstnames":["Alexander","S"],"suffixes":[]},{"propositions":[],"lastnames":["Lalvani"],"firstnames":["Ajit"],"suffixes":[]},{"propositions":[],"lastnames":["Lapierre"],"firstnames":["Simon","Grandjean"],"suffixes":[]},{"propositions":[],"lastnames":["Laurenson"],"firstnames":["Ian","F"],"suffixes":[]},{"propositions":[],"lastnames":["Letcher"],"firstnames":["Brice"],"suffixes":[]},{"propositions":[],"lastnames":["Lin"],"firstnames":["Wan-Hsuan"],"suffixes":[]},{"propositions":[],"lastnames":["Liu"],"firstnames":["Chunfa"],"suffixes":[]},{"propositions":[],"lastnames":["Liu"],"firstnames":["Dongxin"],"suffixes":[]},{"propositions":[],"lastnames":["Malone"],"firstnames":["Kerri","M"],"suffixes":[]},{"propositions":[],"lastnames":["Mandal"],"firstnames":["Ayan"],"suffixes":[]},{"propositions":[],"lastnames":["Mansjö"],"firstnames":["Mikael"],"suffixes":[]},{"propositions":[],"lastnames":["Calisto Matias"],"firstnames":["Daniela","Vicente","Lucena"],"suffixes":[]},{"propositions":[],"lastnames":["Meintjes"],"firstnames":["Graeme","A"],"suffixes":[]},{"propositions":["de Freitas Mendes"],"lastnames":[],"firstnames":["Flávia"],"suffixes":[]},{"propositions":[],"lastnames":["Merker"],"firstnames":["Matthias"],"suffixes":[]},{"propositions":[],"lastnames":["Mihalic"],"firstnames":["Marina"],"suffixes":[]},{"propositions":[],"lastnames":["Millard"],"firstnames":["James"],"suffixes":[]},{"propositions":[],"lastnames":["Miotto"],"firstnames":["Paolo"],"suffixes":[]},{"propositions":[],"lastnames":["Mistry"],"firstnames":["Nerges"],"suffixes":[]},{"propositions":[],"lastnames":["Moore"],"firstnames":["David"],"suffixes":[]},{"propositions":[],"lastnames":["Musser"],"firstnames":["Kimberlee","A"],"suffixes":[]},{"propositions":[],"lastnames":["Ngcamu"],"firstnames":["Dumisani"],"suffixes":[]},{"propositions":[],"lastnames":["Nhung"],"firstnames":["Hoang","Ngoc"],"suffixes":[]},{"propositions":[],"lastnames":["Niemann"],"firstnames":["Stefan"],"suffixes":[]},{"propositions":[],"lastnames":["Nilgiriwala"],"firstnames":["Kayzad","Soli"],"suffixes":[]},{"propositions":[],"lastnames":["Nimmo"],"firstnames":["Camus"],"suffixes":[]},{"propositions":[],"lastnames":["O'Donnell"],"firstnames":["Max"],"suffixes":[]},{"propositions":[],"lastnames":["Okozi"],"firstnames":["Nana"],"suffixes":[]},{"propositions":[],"lastnames":["Oliveira"],"firstnames":["Rosangela","Siqueira"],"suffixes":[]},{"propositions":[],"lastnames":["Omar"],"firstnames":["Shaheed","Vally"],"suffixes":[]},{"propositions":[],"lastnames":["Paton"],"firstnames":["Nicholas"],"suffixes":[]},{"propositions":[],"lastnames":["Peto"],"firstnames":["Timothy","E","A"],"suffixes":[]},{"propositions":[],"lastnames":["Pinhata"],"firstnames":["Juliana","Maira","Watanabe"],"suffixes":[]},{"propositions":[],"lastnames":["Plesnik"],"firstnames":["Sara"],"suffixes":[]},{"propositions":[],"lastnames":["Puyen"],"firstnames":["Zully","M"],"suffixes":[]},{"propositions":[],"lastnames":["Rabodoarivelo"],"firstnames":["Marie","Sylvianne"],"suffixes":[]},{"propositions":[],"lastnames":["Rakotosamimanana"],"firstnames":["Niaina"],"suffixes":[]},{"propositions":[],"lastnames":["Rancoita"],"firstnames":["Paola","M","V"],"suffixes":[]},{"propositions":[],"lastnames":["Rathod"],"firstnames":["Priti"],"suffixes":[]},{"propositions":[],"lastnames":["Robinson"],"firstnames":["Esther","Rhiannon"],"suffixes":[]},{"propositions":[],"lastnames":["Rodger"],"firstnames":["Gillian"],"suffixes":[]},{"propositions":[],"lastnames":["Rodrigues"],"firstnames":["Camilla"],"suffixes":[]},{"propositions":[],"lastnames":["Rodwell"],"firstnames":["Timothy","C"],"suffixes":[]},{"propositions":[],"lastnames":["Roohi"],"firstnames":["Aysha"],"suffixes":[]},{"propositions":[],"lastnames":["Santos-Lazaro"],"firstnames":["David"],"suffixes":[]},{"propositions":[],"lastnames":["Shah"],"firstnames":["Sanchi"],"suffixes":[]},{"propositions":[],"lastnames":["Smith"],"firstnames":["Grace"],"suffixes":[]},{"propositions":[],"lastnames":["Kohl"],"firstnames":["Thomas","Andreas"],"suffixes":[]},{"propositions":[],"lastnames":["Solano"],"firstnames":["Walter"],"suffixes":[]},{"propositions":[],"lastnames":["Spitaleri"],"firstnames":["Andrea"],"suffixes":[]},{"propositions":[],"lastnames":["Steyn"],"firstnames":["Adrie","J","C"],"suffixes":[]},{"propositions":[],"lastnames":["Supply"],"firstnames":["Philip"],"suffixes":[]},{"propositions":[],"lastnames":["Surve"],"firstnames":["Utkarsha"],"suffixes":[]},{"propositions":[],"lastnames":["Tahseen"],"firstnames":["Sabira"],"suffixes":[]},{"propositions":[],"lastnames":["Thuong"],"firstnames":["Nguyen","Thuy","Thuong"],"suffixes":[]},{"propositions":[],"lastnames":["Thwaites"],"firstnames":["Guy"],"suffixes":[]},{"propositions":[],"lastnames":["Todt"],"firstnames":["Katharina"],"suffixes":[]},{"propositions":[],"lastnames":["Trovato"],"firstnames":["Alberto"],"suffixes":[]},{"propositions":[],"lastnames":["Utpatel"],"firstnames":["Christian"],"suffixes":[]},{"propositions":[],"lastnames":["Van Rie"],"firstnames":["Annelies"],"suffixes":[]},{"propositions":[],"lastnames":["Vijay"],"firstnames":["Srinivasan"],"suffixes":[]},{"propositions":[],"lastnames":["Walker"],"firstnames":["A","Sarah"],"suffixes":[]},{"propositions":[],"lastnames":["Walker"],"firstnames":["Timothy","M"],"suffixes":[]},{"propositions":[],"lastnames":["Warren"],"firstnames":["Robin"],"suffixes":[]},{"propositions":[],"lastnames":["Werngren"],"firstnames":["Jim"],"suffixes":[]},{"propositions":[],"lastnames":["Wijkander"],"firstnames":["Maria"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Robert","J"],"suffixes":[]},{"propositions":[],"lastnames":["Wilson"],"firstnames":["Daniel","J"],"suffixes":[]},{"propositions":[],"lastnames":["Wintringer"],"firstnames":["Penelope"],"suffixes":[]},{"propositions":[],"lastnames":["Xiao"],"firstnames":["Yu-Xin"],"suffixes":[]},{"propositions":[],"lastnames":["Yang"],"firstnames":["Yang"],"suffixes":[]},{"propositions":[],"lastnames":["Yanlin"],"firstnames":["Zhao"],"suffixes":[]},{"propositions":[],"lastnames":["Yao"],"firstnames":["Shen-Yuan"],"suffixes":[]},{"propositions":[],"lastnames":["Zhu"],"firstnames":["Baoli"],"suffixes":[]}],"doi":"10.1038/s41467-023-44325-5","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Barilar et al. - 2024 - Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of.pdf:pdf","issn":"2041-1723","journal":"Nature Communications","keywords":"Antibiotics,Antimicrobial resistance,Bacterial genes,Infectious,OA,OA_PMC,Pathogens,disease diagnostics,fund_ack,original","mendeley-tags":"OA,OA_PMC,fund_ack,original","month":"jan","number":"1","pages":"488","pmid":"38216576","publisher":"Nature Publishing Group","title":"Quantitative measurement of antibiotic resistance in <i>Mycobacterium tuberculosis</i> reveals genetic determinants of resistance and susceptibility in a target gene approach","url":"https://www.nature.com/articles/s41467-023-44325-5","volume":"15","year":"2024","bibtex":"@article{Barilar2024,\r\nabstract = {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 susceptibilities in a binary manner (classifying strains as either susceptible or resistant). Here, 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 (MIC) in 15,211 Mycobacterium tuberculosis clinical isolates from 23 countries across five continents. We identified 492 unique MIC-elevating variants across 13 drugs, as well as 91 mutations likely linked to hypersensitivity. Our results advance genetics-based diagnostics for tuberculosis and serve as a curated training/testing dataset for development of drug resistance prediction algorithms. Molecular diagnostics for tuberculosis have focused on predicting drug susceptibilities in a binary manner (i.e., strains are either susceptible or resistant). Here, CRyPTIC Consortium researchers use whole genome sequencing and a quantitative assay to identify associations between genomic mutations and minimum inhibitory concentrations in over 15,000 Mycobacterium tuberculosis clinical isolates.},\r\nauthor = {Barilar, Ivan and Battaglia, Simone and Borroni, Emanuele and Brandao, Angela Pires and Brankin, Alice and Cabibbe, Andrea Maurizio and Carter, Joshua and Chetty, Darren and Cirillo, Daniela Maria and Claxton, Pauline and Clifton, David A and Cohen, Ted and Coronel, Jorge and Crook, Derrick W and Dreyer, Viola and Earle, Sarah G. and Escuyer, Vincent and Ferrazoli, Lucilaine and Fowler, Philip W and Gao, George Fu and Gardy, Jennifer and Gharbia, Saheer and Ghisi, Kelen Teixeira and Ghodousi, Arash and {Gibertoni Cruz}, Ana Lu{\\'{i}}za and Grandjean, Louis and Grazian, Clara and Groenheit, Ramona and Guthrie, Jennifer L and He, Wencong and Hoffmann, Harald and Hoosdally, Sarah J and Hunt, Martin and Iqbal, Zamin and Ismail, Nazir Ahmed and Jarrett, Lisa and Joseph, Lavania and Jou, Ruwen and Kambli, Priti and Khot, Rukhsar and Knaggs, Jeff and Koch, Anastasia and Kohlerschmidt, Donna and Kouchaki, Samaneh and Lachapelle, Alexander S and Lalvani, Ajit and Lapierre, Simon Grandjean and Laurenson, Ian F and Letcher, Brice and Lin, Wan-Hsuan and Liu, Chunfa and Liu, Dongxin and Malone, Kerri M and Mandal, Ayan and Mansj{\\\"{o}}, Mikael and {Calisto Matias}, Daniela Vicente Lucena and Meintjes, Graeme A and {de Freitas Mendes}, Fl{\\'{a}}via and Merker, Matthias and Mihalic, Marina and Millard, James and Miotto, Paolo and Mistry, Nerges and Moore, David and Musser, Kimberlee A and Ngcamu, Dumisani and Nhung, Hoang Ngoc and Niemann, Stefan and Nilgiriwala, Kayzad Soli and Nimmo, Camus and O'Donnell, Max and Okozi, Nana and Oliveira, Rosangela Siqueira and Omar, Shaheed Vally and Paton, Nicholas and Peto, Timothy E A and Pinhata, Juliana Maira Watanabe and Plesnik, Sara and Puyen, Zully M and Rabodoarivelo, Marie Sylvianne and Rakotosamimanana, Niaina and Rancoita, Paola M V and Rathod, Priti and Robinson, Esther Rhiannon and Rodger, Gillian and Rodrigues, Camilla and Rodwell, Timothy C and Roohi, Aysha and Santos-Lazaro, David and Shah, Sanchi and Smith, Grace and Kohl, Thomas Andreas and Solano, Walter and Spitaleri, Andrea and Steyn, Adrie J C and Supply, Philip and Surve, Utkarsha and Tahseen, Sabira and Thuong, Nguyen Thuy Thuong and Thwaites, Guy and Todt, Katharina and Trovato, Alberto and Utpatel, Christian and {Van Rie}, Annelies and Vijay, Srinivasan and Walker, A Sarah and Walker, Timothy M and Warren, Robin and Werngren, Jim and Wijkander, Maria and Wilkinson, Robert J and Wilson, Daniel J and Wintringer, Penelope and Xiao, Yu-Xin and Yang, Yang and Yanlin, Zhao and Yao, Shen-Yuan and Zhu, Baoli},\r\ndoi = {10.1038/s41467-023-44325-5},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Barilar et al. - 2024 - Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of.pdf:pdf},\r\nissn = {2041-1723},\r\njournal = {Nature Communications},\r\nkeywords = {Antibiotics,Antimicrobial resistance,Bacterial genes,Infectious,OA,OA{\\_}PMC,Pathogens,disease diagnostics,fund{\\_}ack,original},\r\nmendeley-tags = {OA,OA{\\_}PMC,fund{\\_}ack,original},\r\nmonth = {jan},\r\nnumber = {1},\r\npages = {488},\r\npmid = {38216576},\r\npublisher = {Nature Publishing Group},\r\ntitle = {{Quantitative measurement of antibiotic resistance in \\textit{Mycobacterium tuberculosis} reveals genetic determinants of resistance and susceptibility in a target gene approach}},\r\nurl = {https://www.nature.com/articles/s41467-023-44325-5},\r\nvolume = {15},\r\nyear = {2024}\r\n}\r\n","author_short":["Barilar, I.","Battaglia, S.","Borroni, E.","Brandao, A. P.","Brankin, A.","Cabibbe, A. M.","Carter, J.","Chetty, D.","Cirillo, D. M.","Claxton, P.","Clifton, D. A","Cohen, T.","Coronel, J.","Crook, D. W","Dreyer, V.","Earle, S. G.","Escuyer, V.","Ferrazoli, L.","Fowler, P. W","Gao, G. F.","Gardy, J.","Gharbia, S.","Ghisi, K. T.","Ghodousi, A.","Gibertoni Cruz, A. L.","Grandjean, L.","Grazian, C.","Groenheit, R.","Guthrie, J. L","He, W.","Hoffmann, H.","Hoosdally, S. J","Hunt, M.","Iqbal, Z.","Ismail, N. A.","Jarrett, L.","Joseph, L.","Jou, R.","Kambli, P.","Khot, R.","Knaggs, J.","Koch, A.","Kohlerschmidt, D.","Kouchaki, S.","Lachapelle, A. S","Lalvani, A.","Lapierre, S. G.","Laurenson, I. F","Letcher, B.","Lin, W.","Liu, C.","Liu, D.","Malone, K. M","Mandal, A.","Mansjö, M.","Calisto Matias, D. V. L.","Meintjes, G. A","de Freitas Mendes , F.","Merker, M.","Mihalic, M.","Millard, J.","Miotto, P.","Mistry, N.","Moore, D.","Musser, K. A","Ngcamu, D.","Nhung, H. N.","Niemann, S.","Nilgiriwala, K. S.","Nimmo, C.","O'Donnell, M.","Okozi, N.","Oliveira, R. S.","Omar, S. V.","Paton, N.","Peto, T. E A","Pinhata, J. M. W.","Plesnik, S.","Puyen, Z. M","Rabodoarivelo, M. S.","Rakotosamimanana, N.","Rancoita, P. M V","Rathod, P.","Robinson, E. R.","Rodger, G.","Rodrigues, C.","Rodwell, T. C","Roohi, A.","Santos-Lazaro, D.","Shah, S.","Smith, G.","Kohl, T. A.","Solano, W.","Spitaleri, A.","Steyn, A. J C","Supply, P.","Surve, U.","Tahseen, S.","Thuong, N. T. T.","Thwaites, G.","Todt, K.","Trovato, A.","Utpatel, C.","Van Rie, A.","Vijay, S.","Walker, A S.","Walker, T. M","Warren, R.","Werngren, J.","Wijkander, M.","Wilkinson, R. J","Wilson, D. J","Wintringer, P.","Xiao, Y.","Yang, Y.","Yanlin, Z.","Yao, S.","Zhu, B."],"key":"Barilar2024","id":"Barilar2024","bibbaseid":"barilar-battaglia-borroni-brandao-brankin-cabibbe-carter-chetty-etal-quantitativemeasurementofantibioticresistanceinimycobacteriumtuberculosisirevealsgeneticdeterminantsofresistanceandsusceptibilityinatargetgeneapproach-2024","role":"author","urls":{"Paper":"https://www.nature.com/articles/s41467-023-44325-5"},"keyword":["Antibiotics","Antimicrobial resistance","Bacterial genes","Infectious","OA","OA_PMC","Pathogens","disease diagnostics","fund_ack","original"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-JLqZ7RwZ3VC2d6ErLGHAtOeMRS_7GCz","dataSources":["Krmt6gt9ktB2s6ARh"],"keywords":["antibiotics","antimicrobial resistance","bacterial genes","infectious","oa","oa_pmc","pathogens","disease diagnostics","fund_ack","original"],"search_terms":["quantitative","measurement","antibiotic","resistance","mycobacterium","tuberculosis","reveals","genetic","determinants","resistance","susceptibility","target","gene","approach","barilar","battaglia","borroni","brandao","brankin","cabibbe","carter","chetty","cirillo","claxton","clifton","cohen","coronel","crook","dreyer","earle","escuyer","ferrazoli","fowler","gao","gardy","gharbia","ghisi","ghodousi","gibertoni cruz","grandjean","grazian","groenheit","guthrie","he","hoffmann","hoosdally","hunt","iqbal","ismail","jarrett","joseph","jou","kambli","khot","knaggs","koch","kohlerschmidt","kouchaki","lachapelle","lalvani","lapierre","laurenson","letcher","lin","liu","liu","malone","mandal","mansjö","calisto matias","meintjes","de freitas mendes ","merker","mihalic","millard","miotto","mistry","moore","musser","ngcamu","nhung","niemann","nilgiriwala","nimmo","o'donnell","okozi","oliveira","omar","paton","peto","pinhata","plesnik","puyen","rabodoarivelo","rakotosamimanana","rancoita","rathod","robinson","rodger","rodrigues","rodwell","roohi","santos-lazaro","shah","smith","kohl","solano","spitaleri","steyn","supply","surve","tahseen","thuong","thwaites","todt","trovato","utpatel","van rie","vijay","walker","walker","warren","werngren","wijkander","wilkinson","wilson","wintringer","xiao","yang","yanlin","yao","zhu"],"title":"Quantitative measurement of antibiotic resistance in <i>Mycobacterium tuberculosis</i> reveals genetic determinants of resistance and susceptibility in a target gene approach","year":2024}