Inside the Personalized Medicine Toolbox : GC×GC-Mass Spectrometry for High-Throughput Profiling of the Human Plasma Metabolome

Personalized medicine advocates have been frustrated by the issue of analyte component resolution in biomolecular profiling. Because complex human biological samples such as plasma, serum, or urine contain ~10^sup 3^-10^sup 7^ unique molecular entities, the analyte capacity of any high-throughput platform is typically exceeded. In our attempt to overcome this problem, we employed the use of comprehensive two-dimensional gas chromatography (GC×GC) combined with time-of-flight mass spectrometry (TOF-MS) for high-throughput profiling of the human plasma metabolome. The profiling experiments demonstrated the capability of a GC×GC-TOF-MS approach with regard to component resolution as well as overall utility for comparative metabolomic analyses employing plasma samples from a "control" cohort (81 samples) versus a cardiovascular-compromised cohort (15 samples) of individuals. The use of the GC×GC separation has resulted in a platform that provides more than an order of magnitude greater resolving power while at the same time not affecting the overall experimental run time. Additionally, the high-throughput approach provides information-rich datasets that can be used to distinguish the control and disease sample cohorts. Such results suggest that high-throughput, high-coverage profiling capabilities, such as those afforded by GC×GC-TOF-MS techniques, can impact the development of personalized medicine in which future disease prevention, diagnosis, and treatment are tailored to an individual's unique molecular makeup. Challenges to full implementation of high-throughput metabolite profiling by GC×GC-TOF-MS as well as future directions are discussed. [PUBLICATION ABSTRACT]