Plasma metabolomic profiles enhance precision medicine for volunteers of normal health.
Precision medicine, taking account of human individuality in genes, environment, and lifestyle for early disease diagnosis and individualized therapy, has shown great promise to transform medical care. Nontargeted metabolomics, with the ability to detect broad classes of biochemicals, can provide a comprehensive functional phenotype integrating clinical phenotypes with genetic and nongenetic factors. To test the application of metabolomics in individual diagnosis, we conducted a metabolomics analysis on plasma samples collected from 80 volunteers of normal health with complete medical records and three-generation pedigrees. Using a broad-spectrum metabolomics platform consisting of liquid chromatography and GC coupled with MS, we profiled nearly 600 metabolites covering 72 biochemical pathways in all major branches of biosynthesis, catabolism, gut microbiome activities, and xenobiotics. Statistical analysis revealed a considerable range of variation and potential metabolic abnormalities across the individuals in this cohort. Examination of the convergence of metabolomics profiles with whole-exon sequences (WESs) provided an effective approach to assess and interpret clinical significance of genetic mutations, as shown in a number of cases, including fructose intolerance, xanthinuria, and carnitine deficiency. Metabolic abnormalities consistent with early indications of diabetes, liver dysfunction, and disruption of gut microbiome homeostasis were identified in several volunteers. Additionally, diverse metabolic responses to medications among the volunteers may assist to identify therapeutic effects and sensitivity to toxicity. The results of this study demonstrate that metabolomics could be an effective approach to complement next generation sequencing (NGS) for disease risk analysis, disease monitoring, and drug management in our goal toward precision care.
Metabolon, Inc., Durham, NC 27713; lguo@metabolon.com tcaskey@bcm.edu.
Lining
L
Guo
Metabolon, Inc., Durham, NC 27713;
Michael V
MV
Milburn
Metabolon, Inc., Durham, NC 27713;
John A
JA
Ryals
Metabolon, Inc., Durham, NC 27713;
Shaun C
SC
Lonergan
Metabolon, Inc., Durham, NC 27713;
Matthew W
MW
Mitchell
Metabolon, Inc., Durham, NC 27713;
Jacob E
JE
Wulff
Metabolon, Inc., Durham, NC 27713;
Danny C
DC
Alexander
Metabolon, Inc., Durham, NC 27713;
Anne M
AM
Evans
Metabolon, Inc., Durham, NC 27713;
Brandi
B
Bridgewater
Metabolon, Inc., Durham, NC 27713;
Luke
L
Miller
Center for Molecular Imaging, Division of Genomics and Bioinformatics, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030;
Manuel L
ML
Gonzalez-Garay
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 lguo@metabolon.com tcaskey@bcm.edu.
C Thomas
CT
Caskey
D002853:Chromatography, Liquid; D015331:Cohort Studies; D008401:Gas Chromatography-Mass Spectrometry; D064368:Healthy Volunteers; D006801:Humans; D055442:Metabolome; D010949:Plasma; D057285:Precision Medicine
disease assessment; functional phenotyping; gene penetrance; metabolomics; whole-exome sequencing