Current challenges in metabolomics: from analytical coverage to strategies and tools for data integration in Chronic Kidney Disease

Serge Rudaz, School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland (serge.rudaz@unige.ch)

Metabolomics, one of the omics technologies that aims to comprehensively analyse the metabolic complexity of biological systems, constitutes a representative example of fast moving research fields taking advantage of recent technological advances to provide extensive sample monitoring. Today, untargeted metabolomics allows a quite large coverage of metabolites (mass < 1000 Da) for phenotype modifications assessment caused by pathologies. As no single technique offers a holistic monitoring of all metabolites in a biofluid, the use of multiple analytical platforms is still needed. Reversed-phase chromatography (RPLC) and hydrophilic interaction chromatography (HILIC) coupled to high resolution mass spectrometry (HRMS) are among the complementary techniques commonly used for their coverage of apolar and polar metabolites, respectively. This strategy based on the integration of data obtained from various analytical approaches was applied to plasma samples collected from a clinical study designed to evaluate the metabolic impact of chronic kidney disease (CKD). CKD is a renal disorder characterized by progressive loss of kidney function leading to end-stage renal disease and high risk of cardiovascular morbidity and mortality, and is one of the major public health issue. Due to the irreversibility of the disease progression, hemodialysis and transplantation are mandatory at end-stage. The first aim was to evaluate metabolic alterations related to CKD severity and highlight new biomarkers which could improve diagnosis. More than 250 annotated compounds were investigated thanks to the fusion of datasets generated from multiple platforms using an in-house database. Then, a study of the metabolome was performed just after dialysis session to assess the impact of hemodialysis on end-stage renal disease (ESRD) patients. Finally, kidney transplantation, which tends to restore healthy near-to-normal kidney filtration, was investigated trough the study of transplanted patients, but also volunteers before and after kidney donation. As presented in this lecture through the CKD example, accounting properly for the structure and inherent properties of metabolomic datasets is mandatory for harnessing their complexity and provide relevant information. In that perspective, advances in analytics as well as chemometrics have a central role to play in the choice of an appropriate methodology.  Multivariate datasets originating from multiblock data collections and longitudinal studies demonstrated the interest of methodological improvement for metabolomics in patient monitoring.

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Abstract Reference & Short Personal Biography of Presenting Author

Serge Rudaz studied pharmacy in Switzerland, where he obtained his PhD in 1997 with Prof. Jean-Luc Veuthey. Later, he joined the National Research Center in Roma (Italy) for a post-doctoral position concerning the application of capillary electrophoresis (CE) hyphenated to mass spectrometry (MS) for chiral separation in biological fluids. From 1998 to 2011, he was a master-assistant in Phytochemistry at the University of Lausanne and then Maître d’Enseignement et de Recherche (MER), where he started to promote new strategies for untargeted MS analyses. He was promoted to Associate Professor in 2012 at the School of Pharmaceutical Sciences, University of Geneva, where he leads the biomedical and metabolomics analysis (BMA) group. Serge Rudaz contributed to the field of analytical sciences with diverse activities, including invited lectures and invited professorships at various Universities. He is a member of several scientific societies and scientific boards. In addition to acting as a research group leader and member of the management board of the Swiss Centre for Applied Human Toxicology (SCAHT) Foundation, he is also President of the Swiss Metabolomics Society (SMS) and vice-president of the Competence Center in Chemical and Toxicological Analysis (ccCTA). Currently, he is interested in metabolomics, (UHP)LC and CE coupled to MS, advances in sample preparation, analysis of pharmaceuticals and falsified medicines, biological matrices, and clinical and preclinical studies, which include metabolism and toxicological analysis. Serge Rudaz is an expert in a variety of chemometric approaches, including experimental design (DOE) validation and regulation (ISO17025), as well as multivariate data analysis (MVA) for metabolomics. He is a (co)author of over 10 book chapters (>10) and 285 peer-reviewed papers, with an H-index (Scopus) of 51. He was chair/co-chair of several national or international congress, such as Chimiométrie 2015, SEP 2017 and MSB 2020.

The group of Serge Rudaz is developing new strategies for targeted and untargeted metabolomics analyses and specializes in the analysis of low molecular weight compounds in biological matrices. Since 2010, the group has also focused on developing chemometric approaches dedicated to the analysis of data produced by MS couplings, including CE. Aspects of dimensionality reduction and multi-table analysis are addressed through collaborative projects in the fields of toxicology, biology, biochemistry, and pharmacology.