TY - JOUR
T1 - Opening up the "black box"
T2 - Metabolic phenotyping and metabolome-wide association studies in epidemiology
AU - Bictash, Magda
AU - Ebbels, Timothy M.
AU - Chan, Queenie
AU - Loo, Ruey Leng
AU - Yap, Ivan K.S.
AU - Brown, Ian J.
AU - De Iorio, Maria
AU - Daviglus, Martha L.
AU - Holmes, Elaine
AU - Stamler, Jeremiah
AU - Nicholson, Jeremy K.
AU - Elliott, Paul
N1 - Funding Information:
The authors thank Elaine Maibaum for acquisition of the INTERMAP NMR spectra, and INTERMAP colleagues at local, national, and international centres. A partial listing of colleagues is provided in reference 10. The INTERMAP Study is supported by grants RO1 HL50490 and RO1 HL084228 , from the National Heart, Lung, and Blood Institute , Bethesda, Maryland; by grant 090357003 from the Ministry of Education, Science, Sports, and Culture , Tokyo, Japan; and by national agencies in the Peoples Republic of China and in the United Kingdom.
PY - 2010/9
Y1 - 2010/9
N2 - 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. Objectives: 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. Discussion: 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. Conclusion: 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.
AB - 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. Objectives: 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. Discussion: 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. Conclusion: 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.
KW - Biomarkers
KW - INTERMAP
KW - INTERSALT
KW - Metabolic phenotyping
KW - Metabonomics
KW - NMR spectroscopy
UR - http://www.scopus.com/inward/record.url?scp=77955655126&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955655126&partnerID=8YFLogxK
U2 - 10.1016/j.jclinepi.2009.10.001
DO - 10.1016/j.jclinepi.2009.10.001
M3 - Review article
C2 - 20056386
AN - SCOPUS:77955655126
VL - 63
SP - 970
EP - 979
JO - American journal of syphilis, gonorrhea, and venereal diseases
JF - American journal of syphilis, gonorrhea, and venereal diseases
SN - 0895-4356
IS - 9
ER -