1. Metabolomics DNA RNA Protein Biochemicals (Metabolites) Genomics – 25,000 Genes Transcriptomics – 100,000 Transcripts Metabolomics – 2,800 Compounds Proteomics – 1,000,000 Proteins

2. Systems Roles DNA RNA Proteins Metabolites The ultimate potential of a cell The current direction of a cell The functional capabilities of a cell The limiting currency of a cell Material Information

3. Mass Distribution of Compounds in the Human Metabolome Mass Number of cmpds per 20 daltons Metabolome –natively biosynthesized –monomeric Complex metabolites Xenobiome

4. Metabolomics is: Precise in Nomenclature & Role Quantitative & Statistically Approachable Pharmaceutically Relevant Less Complex “Integromics”

5. The birth of a science?

6. 2003 NIH Roadmap

7. FDA – Critical Path (2004) DOE – DOE Genomics:GTL ROADMAP (2005)

8. Orthomolecular medicine ‘Orthomolecular diagnosis is the process of determining the concentration of various substances in the body. Most of our experiments on orthomolecular diagnosis have involved the use of gas-liquid chromatography, ion exchange chromatography, or mass spectrometry. In this paper we discuss the approach to this problem that we have developed during the past five years.’ Clin. Chem. 20, 961 - 965 (1974).

9. The birth of a science?

10. Characteristics Chemocentric platform Unbiased analyses Library based compound identification Quantitative Robust Reproducible CVs < 10%

11. MS platforms Sample Preparation GC MS/ei Data Set Software LC MS /+ MS /- Data Extraction -peak identification -peak alignment -peak deconvolution Chemical Identification - reference databases -ion spectra -grouping related ions -compound id Quantitation Quality Control Data Reduction PreparationAnalysisInformatics LIMS