DISCRIMINATION OF DENGUE DISEASE FROM HEALTHY BASED ON THE CHEMOMETRY OF 1H NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
DOI:
https://doi.org/10.11113/jt.v77.6998Keywords:
Dengue, NMR spectroscopy, multivariate analysis, metabolomicsAbstract
Dengue is the most important human viral disease transmitted by arthropod vectors and over half of the world's populations live in areas at risk of infection. The severity of the infection depends on the form of the disease, which can be symptomatic or asymptomatic. Currently there is neither specific treatment nor vaccine to tackle this emerging disease. Metabolomics applied in this study, aimed to provide a global snapshot of all small-molecule metabolites in urine as biological sample of choice to more focused studies of metabolism to distinguish between healthy and dengue infected subjects. Fifty-two patients diagnosed with dengue fever at Penang General Hospital and fourty-three healthy individuals were recruited in this study. 1H-nuclear magnetic resonance (NMR) spectroscopy combined with multivariate analysis (MVA) methods such as principal component analysis (PCA), partial least square discriminant analysis (PLS-DA) and orthogonal PLS-DA (OPLS-DA) were employed for statistical data exploration. The model score plot results showed that all three MVAs showed very good spatial distributions with clear clusters/grouping between healthy individuals and dengue infected individuals. Also, statistically, the PLS-DA and OPLS-DA models had high reproducibility and predictivity values, > 0.5. In conclusion, this study established the potential of using a combination of 1H NMR spectroscopy and multivariate data analyses in differentiating healthy and non-healthy individuals, based on obtained score plots reflecting the metabolites pertubation, where spectral features contributing most to variation or separation are identified for further analysis.
References
Fang, R., Lo, E. and Lim, T. W. 1984. The 1982 Dengue Epidemic In Malaysia: Epidemiological, Serological And Virological Aspects. Southeast Asian Journal of Tropic Medical Public Health. 15: 51–57.
Rudnick, A. Tan, E. E., Lucas, J. K. and Omar, M. B. 1965. Mosquito-Borne Haemorrhagic Fever In Malaya. Britain Medical Journal. 1: 1269–1272.
Poovaneswari, S. 1993. Dengue Situation In Malaysia. Malaysia Journal Of Pathology. 15: 3-7.
Ahmad Nizal, M. G., Rozita, H., Mazrura, S., Zainudin, M. A., Hidayatulfathi, O., Faridah, M. A., Noor Artika, I. and Er, A. C. 2012. Dengue Infections And Circulating Serotypes In Negeri Sembilan, Malaysia. Malaysian Journal of Public Health Medicine.12: 21-30.
Muhammad Azami, N. A., Salleh, S. A. , Neoh, H. M., Syed Zakaria, S. Z. and Jamal, R. 2011. Dengue Epidemic In Malaysia: Not A Predominantly Urban Disease Anymore. BMC Research Notes. 4: 216.
Fiehn, O. 2002. Metabolomics – The Link Between Genotypes And Phenotypes. Plant Molecular Biology. 48(1-2): 155-171.
Shahfiza, N. et al. 2015. Metabolomics For Characterization Of Gender Differences In Patients Infected With Dengue Virus. Asian Pacific Journal of Tropical Medicine. http:// dx.doi.org/10.1016/j.apjtm.2015.05.012.
Birungi, G., Chen, S. M., Loy, B. P., Ng, M. L. and Li, S. F. Y. 2010. Metabolomics Approach For Investigation Of Effects Of Dengue Virus Infection Using The EA.hy926 Cell Line. Journal of Proteome Research. 9: 6523-6634.
Shin, J. H., Yang, J. Y., Jeon, B. Y., Yoon, Y. J., Cho, S. N., Kang, Y. H., Ryu, D. H., Hwang, G. S. 2011. 1H NMR-Based Metabolomic Profiling In Mice Infected With Mycobacterium Tuberculosis. Journal of Proteome Research. 10(5): 2238-2247.
Slupsky, C. M. 2010. NMR-Based Analysis Of Metabolites In Urine Provides Rapid Diagnosis And Etiology Of Pneumonia. Biomarkers Medicine. 4(2): 195-197.
Lakshmanan, V., Rhee, K. Y., Wang, W., Yu, Y., Khafizov, K., Fiser, A., Wu, P., Ndir, O., Mboup, S., Ndiaye, D. and Daily, J. P. 2012. Metabolomic Analysis Of Patient Plasma Yields Evidence Of Plant-Like Α-Linolenic Acid Metabolism In Plasmodium Falciparum. Journal of Infectious Disease. 206(2): 238-248.
Gebregiworgis, T and Powers, R. 2012. Application of NMR Metabolomics To Search For Human Disease Biomarkers. Combinatorial Chemistry & High Throughput Screening. 15: 595-610.
Goodacre, R., Broadhurst, D., Smilde, A. K., Kristal, B. S., Baker, J. D., Beger, R., Bessant, C., Connor, S., Capuani, G., Craig, A., Ebbels, T., Kell, D. B., Manetti, C., Newton, J., Paternostro, G., Somorjai, R., Sjöström, M., Trygg, J. and Wulfert, F. 2007. Proposed Minimum Reporting Standards For Data Analysis In Metabolomics. Metabolomics. 3: 231-241.
Bouatra, S., Aziat, F., Mandal, R., Guo, A. C., Wilson, M. R. et al. 2013. The Human Urine Metabolome. PLoS ONE. 8: e73076.
Bernardo, C. D. N., Nogueira, M. C. O., D. Aquino, É. P., Schmidtke, S., D. Azeredo, E. L. et al. 2012. With NMR Towards New Diagnostic Methods For Dengue. Journal of Analytical Bioanalysis Techniques. 3: 140.
Hicks, J., Sivakolundu, S. and Colson, K. 2009. Metabolomics Guide User Manual Version 005. Bruker Biospin. Billerica, USA.
Zhou, A., Ni, J., Xu, Z., Wang, Lu, S., Sha, W., Karakousis, P. C. and Yao, Y. F. 2013. Application Of 1H NMR Spectroscopy-Based Metabolomics To Sera Of Tuberculosis
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