Plasma metabolomic profiles enhance precision medicine for volunteers of normal health

• DOI: 10.1073/pnas.1508425112
• Publication Date: 2015-08-18T02:41:06Z
• Authors: Lining Guo; Michael V. Milburn; John A. Ryals; Shaun C. Lonergan; Matthew W. Mitchell; Jacob E. Wulff; Danny C. Alexander; Anne M. Evans; Brandi Bridgewater; Luke Miller; Manuel L. Gonzale...; C. Thomas Caskey
• Keywords: Cohort Studies; 0301 basic medicine; Plasma; 03 medical and health sciences; Metabolome; Humans; Precision Medicine; Gas Chromatography-Mass Spectrometry; Healthy Volunteers; Chromatography, Liquid; 3. Good health

Significance Metabolomics has been increasingly recognized as a powerful functional tool that integrates the impacts from genetics, environment, microbiota, and xenobiotics. We used a broad-spectrum metabolomics platform to analyze plasma samples from 80 adults of normal health. The comprehensive metabolic profiles provided a functional readout to assess the penetrance of gene mutations identified by whole-exome sequencing on these individuals. Conversely, metabolic abnormalities identified by statistical analysis uncovered potential damaging mutations that were previously unappreciated. Additionally, we found metabolic signatures consistent with early signs of disease conditions and drug effects associated with efficacy and toxicity. Our findings demonstrate that metabolomics could be an effective tool in precision medicine for disease risk assessment and customized drug therapy in clinics.