Discovery and validation of an NMR-based metabolomic profile in urine as TB biomarker
Por:
Izquierdo-Garcia, JL, Comella-del-Barrio, P, Campos-Olivas, R, Villar-Hernandez, R, Prat-Aymerich, C, De Souza-Galvao, ML, Jimenez-Fuentes, MA, Ruiz-Manzano, J, Stojanovic, Z, Gonzalez, A, Serra-Vidal, M, Garcia-Garcia, E, Muriel-Moreno, B, Millet, JP, Molina-Pinargote, I, Casas, X, Santiago, J, Sabria, F, Martos, C, Herzmann, C, Ruiz-Cabello, J and Dominguez, J
Publicada:
18 dic 2020
Ahead of Print:
18 dic 2020
Resumen:
Despite efforts to improve tuberculosis (TB) detection, limitations in access, quality and timeliness of diagnostic services in low- and middle-income countries are challenging for current TB diagnostics. This study aimed to identify and characterise a metabolic profile of TB in urine by high-field nuclear magnetic resonance (NMR) spectrometry and assess whether the TB metabolic profile is also detected by a low-field benchtop NMR spectrometer. We included 189 patients with tuberculosis, 42 patients with pneumococcal pneumonia, 61 individuals infected with latent tuberculosis and 40 uninfected individuals. We acquired the urine spectra from high and low-field NMR. We characterised a TB metabolic fingerprint from the Principal Component Analysis. We developed a classification model from the Partial Least Squares-Discriminant Analysis and evaluated its performance. We identified a metabolic fingerprint of 31 chemical shift regions assigned to eight metabolites (aminoadipic acid, citrate, creatine, creatinine, glucose, mannitol, phenylalanine, and hippurate). The model developed using low-field NMR urine spectra correctly classified 87.32%, 85.21% and 100% of the TB patients compared to pneumococcal pneumonia patients, LTBI and uninfected individuals, respectively. The model validation correctly classified 84.10% of the TB patients. We have identified and characterised a metabolic profile of TB in urine from a high-field NMR spectrometer and have also detected it using a low-field benchtop NMR spectrometer. The models developed from the metabolic profile of TB identified by both NMR technologies were able to discriminate TB patients from the rest of the study groups and the results were not influenced by anti-TB treatment or TB location. This provides a new approach in the search for possible biomarkers for the diagnosis of TB.
Filiaciones:
Izquierdo-Garcia, JL:
BRTA Basque Res & Technol Alliance, CIC biomaGUNE Ctr Cooperat Res Biomat, Donostia San Sebastian, Gipuzkoa, Spain
Inst Salud Carlos III, CIBER Enfermedades Resp CIBERES, Madrid, Spain
Univ Complutense Madrid, Fac Farm, Madrid, Spain
Comella-del-Barrio, P:
Inst Salud Carlos III, CIBER Enfermedades Resp CIBERES, Madrid, Spain
Hosp Univ Germans Trias i Pujol, Inst Invest Germans Trias i Pujol, Serv Microbiol, Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona, Spain
Campos-Olivas, R:
CNIO Ctr Nacl Invest Oncol, Madrid, Spain
:
Inst Salud Carlos III, CIBER Enfermedades Resp CIBERES, Madrid, Spain
Hosp Univ Germans Trias i Pujol, Inst Invest Germans Trias i Pujol, Serv Microbiol, Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona, Spain
:
Inst Salud Carlos III, CIBER Enfermedades Resp CIBERES, Madrid, Spain
Hosp Univ Germans Trias i Pujol, Inst Invest Germans Trias i Pujol, Serv Microbiol, Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona, Spain
Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands
De Souza-Galvao, ML:
Hosp Univ Vall dHebron, Unitat TB Drassanes, Serv Pneumol, Barcelona, Spain
Jimenez-Fuentes, MA:
Hosp Univ Vall dHebron, Unitat TB Drassanes, Serv Pneumol, Barcelona, Spain
:
Inst Salud Carlos III, CIBER Enfermedades Resp CIBERES, Madrid, Spain
Hosp Univ Germans Trias i Pujol, Serv Pneumol, Barcelona, Spain
Stojanovic, Z:
Inst Salud Carlos III, CIBER Enfermedades Resp CIBERES, Madrid, Spain
Hosp Univ Germans Trias i Pujol, Serv Pneumol, Barcelona, Spain
Gonzalez, A:
Inst Salud Carlos III, CIBER Enfermedades Resp CIBERES, Madrid, Spain
Hosp Univ Germans Trias i Pujol, Serv Pneumol, Barcelona, Spain
Serra-Vidal, M:
Hosp Univ Germans Trias i Pujol, Inst Invest Germans Trias i Pujol, Serv Microbiol, Barcelona, Spain
Garcia-Garcia, E:
Hosp Univ Germans Trias i Pujol, Inst Invest Germans Trias i Pujol, Serv Microbiol, Barcelona, Spain
:
Hosp Univ Germans Trias i Pujol, Inst Invest Germans Trias i Pujol, Serv Microbiol, Barcelona, Spain
Millet, JP:
Unitat Clin Tractament Directament Observat TB, Serv Clin, Barcelona, Spain
Inst Salud Carlos III, CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain
Molina-Pinargote, I:
Unitat Clin Tractament Directament Observat TB, Serv Clin, Barcelona, Spain
Casas, X:
Unitat Clin Tractament Directament Observat TB, Serv Clin, Barcelona, Spain
Santiago, J:
Unitat Clin Tractament Directament Observat TB, Serv Clin, Barcelona, Spain
Sabria, F:
Hosp St Joan Despi Moises Broggi, Serv Pneumol, Barcelona, Spain
Martos, C:
Hosp St Joan Despi Moises Broggi, Serv Pneumol, Barcelona, Spain
Herzmann, C:
Res Ctr Borstel, Ctr Clin Studies, Borstel, Germany
Ruiz-Cabello, J:
BRTA Basque Res & Technol Alliance, CIC biomaGUNE Ctr Cooperat Res Biomat, Donostia San Sebastian, Gipuzkoa, Spain
Inst Salud Carlos III, CIBER Enfermedades Resp CIBERES, Madrid, Spain
Univ Complutense Madrid, Fac Farm, Madrid, Spain
Basque Fdn Sci, Ikerbasque, Bilbao, Vizcaya, Spain
:
Inst Salud Carlos III, CIBER Enfermedades Resp CIBERES, Madrid, Spain
Hosp Univ Germans Trias i Pujol, Inst Invest Germans Trias i Pujol, Serv Microbiol, Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona, Spain
Green Published, gold
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