Advances in Genetics , Proteomics , and Metabolomics Metabolomics Ready for the Prime Time ?

Metabolomics is one of the most rapidly growing areas of contemporary science. Although classic genetics aims to link variations in the DNA sequence directly to distinct phenotypes, “-omic” technologies allow us to shift the focus from the specific gene to the actual effects of the gene itself. Because neither the transcriptional or protein profile can be directly correlated with metabolite concentrations, the importance of measuring small-molecule metabolites has become increasingly clear. In view of the rapid progress in metabolomic techniques, metabolomics is expected to become more widely applied to cardiovascular research. Metabolomics brings the promise of the identification of potential biomarkers and alterations in biochemical pathways, which will facilitate the transition from a reductionistic approach to a more integrated science. Because the relative lack of attention given to the system behavior hampers our progress in translating basic science research into clinical applications, the holistic nature of these emerging techniques may yield valuable new strategies for the prevention and treatment of cardiovascular diseases. By analogy to the genome, the metabolome is defined as the total complement of small-molecule metabolites found in or produced by an organism. The most recent estimates place the number of endogenous metabolites (metabolites synthesized by enzymes encoded in the human genome) at approximately a few thousand, far less than had been previously predicted.1 Importantly, the size of the exogenous metabolome (metabolites not synthesized in the body but consumed as food or generated by host-specific microbes) is far greater, and there is often a spatial separation between metabolite synthesis and use. Hence, although genes, proteins, and metabolites are intimately connected in biological systems and their interactions with environmental changes are reflected in the metabolome,2 gene or protein expression may not directly correlate to metabolite concentrations from the same region (Figure 1). Thus, there is a clear need for an additional readout at the metabolite level, and the promise of “metabolomic profiling” is to achieve a quantitative and qualitative assessment of a subset of metabolites in complex samples such as bodily fluids and tissues.