Characterizing phenotype with tracer based metabolomics.

In the post-genomic era, a pressing challenge to biological scientists is to understand the organization of gene functions, the interaction between gene and nutrient environment, and the genesis of phenotypes. Metabolomics, the quantitation of low molecular weight compounds, has been used to provide a phenotypic description of a cell or tissue by a set of metabolites. Gene function is hypothesized from its correlation with the corresponding set of macromolecules by transcriptomics or proteomics. Another approach to genotype-phenotype correlation is by the reconstruction of genome-scale metabolic maps. The utilization of specific pathways as predicted by reaction network analysis provides the phenotypic characterization of a cell, which can be plotted on a phenotypic phase plane. Tracer based metabolomics is the experimental approach to reaction network analysis using stable isotope tracers. The redistribution of the isotope tracer among metabolic intermediates is used to identify a finite number of pathways, the utilization of which is characteristic of the phenotypic behavior of cells. In this paper, we review tracer based metabolomic methods for the construction of phenotypic phase plane plots, and discuss the functional implications of phenotypic phase plane analysis. Examples of phenotypic changes in response to differentiation, inhibition of signaling pathways and perturbation in nutrient environment are provided.