Diogo de Oliveira (Presenter)
University of Campinas
Bio: Pharmacist, holding an MSc and PhD in analytical chemistry focused in biosciences. With a strong emphasis in mass spectrometry, my research embraces all aspects of the technique, especially the development of easier and more practical workflows to yield accurate and reliable results. Currently I am working on the metabolomics of Zika virus, using MS to thoroughly explore all its aspects and provide useful tools in diagnosis and fast screening approaches.
Authorship: Diogo N. de Oliveira (1), Rafael Gustavo Martins Rodrigues (1), Karen Noda Morishita (1), Estela de O. Lima (1), Carlos F. O. R. Melo (1), Cynthia Silveira (2), Antônio A. M. da Silva (3), Rosβngela F. Batista (3), Maria J. R. Doriqui (3), Patricia S. Carvalho (3), José L. Proença-Módena (4), Denise P. Cavalcanti (2), Rodrigo R. Catharino (1)
(1) Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, (2) Medical Genetics Department, School of Medical Sciences, University of Campinas, (3) Universidade Federal do Maranhão, (4) Genetics, Evolution and Bioagents Department, Biology Institute, University of Campinas
This work applies high-resolution mass spectrometry to identify lipidomic differences between the saliva of infants with microcephaly that were exposed to Zika virus during pregnancy vs. control infants (i.e. no microcephaly and no exposure to Zika virus). We intend to identify and characterize lipids and related molecules that are directly linked to compromised metabolic pathways due to Zika infection, potentially providing insight on how the infection affects fetal development during pregnancy.
The search for risk factors that might be associated with Zika virus (ZIKV) congenital syndrome undergoes difficulties of associating genotype and phenotype, in either health or sick patients. The interaction between gene products and all other intracellular components is the basis for the access of biological systems as a whole. Lipids represent the largest group of molecules inside a metabolome, acting not just as membrane components, but also in cell signaling and hormone synthesis. Lipidomics can provide useful information to compare health and disease conditions and identify differences between them, obtaining a cell physiology profile (phenotype), according to that current situation. The use of high-resolution mass spectrometry (HRMS) as a powerful tool for lipidomics is currently well-known, and is the most suitable approach to provide an accurate and thorough picture of the existing lipid metabolites in any given matrix. For this study, we employ the HRMS-lipidomics platform to assess differences between saliva samples of infants with ZIKV-related microcephaly and control infants, striving to provide valuable information on the metabolic pathways affected by ZIKV during pregnancy.
ZIKV patients were recruited from the Northeast of Brazil, while control subjects were recruited from the Southeast. 1 mL of saliva was collected using a cotton swab. 50 microliters of the sample were diluted to a final volume of 1 mL using methanol:water (70:30). The obtained solution was directly infused into an ESI-LTQ-XL Orbitrap Discovery instrument (Thermo Scientific, Bremen, Germany), where survey spectra were recorded in the m/z range of 50-2000 in both positive and negative ion modes. Data were processed into a matrix of mass vs. intensity, and were submitted to partial least squares discriminant analysis (PLS-DA) using the online platform Metaboanalyst 3.0 (www.metaboabalyst.ca). Characteristic biomarkers for the microcephaly condition will be elected and submitted to characterization, with the support of metabolomics and lipidomics databases such as LipidMaps (www.lipidmaps.org) and the Human Metabolome Database (www.hmdb.ca).
The employed statistical model has proven to be efficient in separating both groups accurately. PLS-DA provided a list of important features that are characteristic to the microcephaly group, i.e. the selected features were either present in the ZIKV group only, or its presence in the control group was below the signal-to-noise ratio. The study is currently in the biomarker election and elucidation phase.
Conclusions & Discussion
we expect to characterize a series of biomarkers that make sense within a biochemical context, thus providing key pathways that are involved with ZIKV infection during pregnancy.
References & Acknowledgements:
We acknowledge the Brazilian Initiative to Fight Aedes aegypti and Microcephaly [Plano Nacional de Enfrentamento ao Aedes aegypti e Microcefalia] from the Brazilian Ministry of Health for the financial support under project No. 88887.137889/2017-00.
IP Royalty: no
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