Investigations of the effects of gender, diurnal variation, and age in human urinary metabolomic profiles.
Metabolomics may have the capacity to revolutionize disease diagnosis through the identification of scores of metabolites that vary during environmental, pathogenic, or toxicological insult. NMR spectroscopy has become one of the main tools for measuring these changes since an NMR spectrum can accurately identify metabolites and their concentrations. The predominant approach in analyzing NMR data has been through the technique of spectral binning. However, identification of spectral areas in an NMR spectrum is insufficient for diagnostic evaluation, since it is unknown whether areas of interest are strictly caused by metabolic changes or are simply artifacts. In this paper, we explore differences in gender, diurnal variation, and age in a human population. We use the example of gender differences to compare traditional spectral binning techniques (NMR spectral areas) to novel targeted profiling techniques (metabolites and their concentrations). We show that targeted profiling produces robust models, generates accurate metabolite concentration data, and provides data that can be used to help understand metabolic differences in a healthy population. Metabolites relating to mitochondrial energy metabolism were found to differentiate gender and age. Dietary components and some metabolites related to circadian rhythms were found to differentiate time of day urine collection. The mechanisms by which these differences arise will be key to the discovery of new diagnostic tests and new understandings of the mechanism of disease.
Slupsky
Carolyn M
CM
Department of Medicine and Magnetic Resonance Diagnostic Centre, University of Alberta, Edmonton, Alberta, Canada. carolyn.slupsky@ualberta.ca
Rankin
Kathryn N
KN
Wagner
James
J
Fu
Hao
H
Chang
David
D
Weljie
Aalim M
AM
Saude
Erik J
EJ
Lix
Bruce
B
Adamko
Darryl J
DJ
Shah
Sirish
S
Greiner
Russ
R
Sykes
Brian D
BD
Marrie
Thomas J
TJ
D000108:Acetylcarnitine / Q000652:urine; D000328:Adult; D000367:Age Factors; D002331:Carnitine / Q000652:urine; D002940:Circadian Rhythm / Q000502:physiology*; D003401:Creatine / Q000652:urine; D005260:Female; D005650:Fumarates / Q000652:urine; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D014551:Urinary Tract / Q000378:metabolism*
D005650:Fumarates; D000108:Acetylcarnitine; D003401:Creatine; D002331:Carnitine