Advancing metabolomics and precision medicine through novel mass spectrometry technologies

Why is metabolomics important?
Metabolomics is the large-scale study of metabolites in biofluids, tissue extracts, or organisms. Metabolites are small (<1000 Da), biologically active molecules such as glucose, cholesterol, creatinine, hormones, lipids, and more.

Metabolomics provides valuable insight into the underlying processes of cells, diseases and, in turn, human health. Metabolites are the ultimate effectors of the cellular machinery, and represent the penultimate step in the progression from the genome, to proteome, to metabolome, to the phenotype.

By studying the metabolome, researchers can measure the dynamics of the cell response to internal or external perturbations, to build a better understanding of the underlying biology from the cell level to the organism level across all species. Such information supports the identification of biomarkers and biological pathways that are active or dormant during states of disease or health.

Why do we need precision medicine?
Currently, patients are treated universally according to their disease diagnosis. However, many widely used drugs are ineffective for at least half of patients with diseases such as arthritis, diabetes, asthma, and depression. With the help of biomarkers and companion diagnostics (diagnostic tests used as a companion to a therapeutic drug to determine its applicability to a specific patient), researchers can stratify patients into subsets according to their disease progression and other key factors. This allows better prediction of disease outcomes so that more appropriate treatment regimes can be developed for the different sub groups. In turn, stratified medicine can give rise to precision medicine, where treatment is tailored for each patient according to their medical history, results from other tests, their response to medication and other clinical features.

How can metabolomics enable precision medicine?
Collecting comprehensive metabolomics data depends on the simultaneous identification and quantification of hundreds of compounds in every sample. This requires robust, powerful and high-throughput mass spectrometry technologies with a very wide dynamic range to accommodate the diverse set of metabolic components present in a typical sample. Mass spectrometry has been heavily employed in this area due to the sensitivity delivered against other available technologies. With the growing interest in precision medicine, biomedical researchers are becoming increasingly dependent on fast, robust and accurate mass spectrometry-based technologies for comprehensive data collection on an industrialized scale. Users will demand ever-high throughput and accuracy for the rapid and reliable identification and quantification of every compound in thousands of samples.

Solutions
SCIEX offers several market-leading mass spectrometry solutions for metabolomics researchers who are conducting targeted screening of known compounds or carrying out discovery research to globally study the metabolome.

• The latest instruments include the X500R QTOF System for Routine Metabolomics, the TripleTOF^® 6600 System, and the QTRAP^® 6500+ System
• SCIEX technology also enables SWATH^® Acquisition, a groundbreaking data independent acquisition (DIA) technique that simultaneously allows comprehensive identification and quantification of virtually every detectable compound in a sample from a single analysis
• For more information about SCIEX technologies for metabolomics, see the “Solutions for Metabolomics and Lipidomics Research” Webinar from Professor Oliver Fiehn, University of California, Davis

For metabolomics researchers performing longitudinal studies of large cohorts, SWATH Acquisition offers the robust workflow required to accurately identify and quantify nearly every detectable relevant metabolite in the sample. SWATH allows data to enter a permanent digital archive that can be re-interrogated at any time in the future.

Recent advances in mass spec for metabolomics and precision medicine

• West Coast Metabolomics Centre, UC Davis, California, USA – Professor Oliver Fiehn has pioneered developments and applications in the field of metabolomics. His research aims at understanding metabolism on a comprehensive level in human population cohorts, animal and plant models, and cells and microorganisms. The Fiehn lab employs the TripleTOF 6600 System for untargeted metabolomics studies when applied to large sample cohorts. The lab predominantly utilizes SWATHAcquisition for these untargeted workflows because all the information can be collected in a single analysis. Download Webinar Series >
• Netherlands Metabolomics Centre, Leiden Academic Centre for Drug Research (LACDR), Leiden University, The Netherlands – Professor Thomas Hankemeier is involved with developing innovative analytical tools for metabolomics. His research has focused on developing improved methods for analyzing as many metabolites as possible in a biological sample. He uses a variety of technologies including SCIEX LC-MS/MS Systems that can provide comprehensive and robust analysis of metabolites in thousands of samples. He is also involved in multi-omics research that brings together genomics, metabolomics, and systems pathology technologies to provide detailed information about the phenome that could be used for informing new treatment options.
• Leiden University Medical Center (LUMC), Leiden University, The Netherland – Dr. Martin Giera at the LUMC is applying metabolomics and lipidomics (analysis of the set of lipid species present in an organism) applications to gain new insights into diagnostic markers of disease. He is using the Lipidyzer™ Platform to analyze biological samples, to identify and quantify over a thousand lipids that impact human health. This novel research will not only provide detailed information about the human lipidome but will also allow discovery of new biomarkers. Read the Case Study >

Future Directions
There is increasing interest within the scientific community in applying multi-omics approaches, where data from genomic, metabolomic, phenotypic and other studies are brought together to better inform stratified medicine approaches, and ultimately enable precision medicine.

Want to learn more about metabolomics and precision medicine?