Comprehensive metabolic profiling or “metabolomics” is a technology that can define the chemical phenotype of human subjects, animal and cell models. This technology allows for the discovery of biomarkers that predict disease incidence, severity, and progression, and sheds light on underlying mechanistic abnormalities. The DMPI Metabolomics Laboratory is a leader in applying both targeted and non-targeted mass spectrometry (MS) based metabolic profiling in the quest to understand disease and its biological mechanisms. The lab is an integral component of the suite of technologies available to collaborators via the DMPI Storefront portal.
The DMPI Metabolomics Laboratory has a comprehensive suite of seven MS instruments that allow both targeted and non-targeted metabolomics assays to be conducted on a wide array of sample types including plasma, blood spots, tissue, urine, cerebral spinal fluid, and cell culture. For targeted analyses, the lab deploys four triple quadrupole (MS/MS) instruments and two gas chromatography (GC)/MS instruments to measure more than 200 specific metabolites across seven chemical classes: 1) acylcarnitines; 2) amino acids and urea cycle intermediates 3) acyl CoAs species; 4) organic acids; 5) ceramides; 6) sphingomyelins and ceramides and 7) nucleotides and purine/pyrimidine pathway intermediates. Accurate quantitation of the metabolites in the targeted assays is achieved using isotope dilution techniques and quality control calibrators.
To complement the strong targeted platform, non-targeted metabolomic methods have been developed to greatly expand coverage of the metabolome across many biochemical classes of metabolites. In collaboration with Agilent Technologies, Inc., the laboratory has created one of the world’s largest retention-time-indexed spectral libraries of metabolites for use in non-targted GC/MS analyses, allowing rapid identification of metabolites that reveal novel biochemical pathways. Another non-targeted approach under active development uses high-performance liquid chromatography (HPLC)-MS. This method involves reverse-phase LC coupled to a quadrupole, time-of-flight mass spectrometer which operates in both positive and negative ionization modes. This high resolution platform provides tremendous expansion in the coverage of the metabolome.
A key feature of the DMPI metabolomics core laboratory is its long experience with collaborative projects, affording a level of experience in data interpretation and translation not found in most other labs of its kind. This experience is provided to potential collaborators via the DMPI’s new Storefront laboratory. The Storefront Laboratory employs dedicated PhD-level personnel that are equipped to assist collaborators with interpretation of various kinds of metabolomics data sets in physiologic and pathophysiologic contexts. In addition, Storefront scientists can draw upon the expertise of senior DMPI faculty when needed, thereby increasing the probability that our collaborative projects will have a productive outcome. Firmly supporting this statement, the DMPI Metabolomics core laboratory has so far co-authored >140 publications in leading scientific journals! Recent highlights include studies of malnutrition resuscitation in a pediatric Ugandan cohort (1), the influence of the microbiome on obesity and metabolism (2), and studies of diabetes risk prediction (3).
DMPI Shared Resource used by the Metabolomics Research Group.