NMR BASED METABOL(N)OMICS: SETTING UP A LABORATORY FOR BIOMARKER DISCOVERY FOR EARLY DISEASE DIAGNOSIS

HOIJEMBERG, PABLO ARIEL

Santa Fe

Workshop; III Workshop de Resonancia Magnética "NMR and EPR at the Forefront of Research"; 2016

Departamento de Física de la Facultad de Bioquímica y Ciencias Biológicas de la Universidad Nacional del Litoral

Metabolomics is defined as ?a comprehensive and quantitative analysis of all metabolites?, and metabonomics is defined as ?the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification?.1 Both terms overlap and are now used interchangeably. Metabolomic studies are interdisciplinary, potentially involving chemists, biologists, biochemists, bioinformaticians and specialists from the medical or veterinary side.Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) have been used as analytical platforms for metabolomic studies for over two decades, with complementary advantages. Though less sensitive than MS, NMR is more robust and reproducible. NMR is speedy, non-destructive and quantitative, and it requires minimal sample preparation. Despite the lack of separation of the metabolites NMR provides information on the molecular structure. Both biofluids and tissues can be analyzed by NMR, including intact tissues with high resolution magic angle spinning probes (hrMAS).After the experimental design, sample collection and preparation, NMR based metabolomics requires careful and consistent spectra acquisition and processing. The data matrix obtained is then analyzed by multivariate data analysis (MVDA) and also by Statistical TOtal Correlation SpectroscopY (STOCSY).2 These analyses can be integrated for biomarker discovery for early disease diagnosis in an untargeted metabolomic study, as MVDA picks up latent structures on the data matrix, while STOCSY finds correlations between NMR signals that would belong to a given metabolite, and thus contributes to metabolite identification. Once biomarker candidates are identified, the affected metabolic pathways can be recognized and a targeted study can be designed with a similar workflow to continue towards the validation of a diagnosis test.Unlike other institutions that perform metabolomic studies in Argentina with either analytical platform (e.g. PLABEM, INTA and INQUISAL), CIBION was conceived to be able to contribute to the field integrating both MS and NMR spectroscopy, having researchers being trained abroad in the specific fields. The MS lab, leaded by Dr. María Eugenia Monge, is already set up and running, while the NMR lab is expecting funding to purchase adequate instrumentation, including a hrMAS probe, which would be the first in Argentina. The first projects currently under study involve biomarker discovery for renal carcinoma and prostate cancer. Queries from interested potential scholars are welcome.