Opening up the "Black Box": metabolic phenotyping and metabolome-wide association studies in epidemiology.
BACKGROUND
Metabolic phenotyping of humans allows information to be captured on the interactions between dietary, xenobiotic, other lifestyle and environmental exposures, and genetic variation, which together influence the balance between health and disease risks at both individual and population levels.


OBJECTIVE
We describe here the main procedures in large-scale metabolic phenotyping and their application to metabolome-wide association (MWA) studies.


METHODS
By use of high-throughput technologies and advanced spectroscopic methods, application of metabolic profiling to large-scale epidemiologic sample collections, including metabolome-wide association (MWA) studies for biomarker discovery and identification.


CONCLUSIONS
Metabolic profiling at epidemiologic scale requires optimization of experimental protocol to maximize reproducibility, sensitivity, and quantitative reliability, and to reduce analytical drift. Customized multivariate statistical modeling approaches are needed for effective data visualization and biomarker discovery with control for false-positive associations since 100s or 1,000s of complex metabolic spectra are being processed.


CONCLUSIONS
Metabolic profiling is an exciting addition to the armamentarium of the epidemiologist for the discovery of new disease-risk biomarkers and diagnostics, and to provide novel insights into etiology, biological mechanisms, and pathways.
Bictash
Magda
M
Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
Ebbels
Timothy M
TM
Chan
Queenie
Q
Loo
Ruey Leng
RL
Yap
Ivan K S
IK
Brown
Ian J
IJ
de Iorio
Maria
M
Daviglus
Martha L
ML
Holmes
Elaine
E
Stamler
Jeremiah
J
Nicholson
Jeremy K
JK
Elliott
Paul
P
D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D055442:Metabolome / Q000235:genetics*; D055432:Metabolomics / Q000379:methods* / Q000592:standards; D017720:Molecular Epidemiology / Q000592:standards*; D010641:Phenotype; D015203:Reproducibility of Results; D018570:Risk Assessment
D015415:Biomarkers