Global Metabolomics Technology and Its Application in Toxicology- Clinical and Preclinical Case Studies; How to use metabolomics for patient stratification (cisplatin treatment) and early preclinical biomarker discovery (renal and liver toxicity)

Abstract

Global metabolomics is a new and powerful technology that can provide a relatively complete picture of metabolism in biological systems. We have developed an unbiased global metabolomics platform based on a combination of three independent systems: ultrahigh performance liquid chromatography/tandem mass spectrometry (UHLC/MS/MS²) optimized for basic species, UHLC/MS/MS² optimized for acidic species, and gas chromatography/mass spectrometry (GC/MS). Rapid identification of metabolites in the experimental samples with high-confidence is achieved by automated comparison of the ion features in the experimental samples to a comprehensive chemical reference library. This platform can provide a very comprehensive coverage of all major cellular pathways. After data generation, integrated tools including statistical analysis, pathway mapping, and data visualization can rapidly provide powerful insights for understanding biological systems. We applied this technology in both preclinical and clinical toxicology (preclinical and clinical safety). Case studies both relying on traditional study design and genome wide association to understand mechanisms of toxicity and identify predicative biomarkers will be discussed.