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Biological Variability Dominates and Influences Analytical Variance in HPLC‐ECD Studies of the Human Plasma Metabolome
Author(s) -
Kristal Bruce S.,
Shurubor Yevgeniya I.,
Matson Wayne R,
Willett Walter C,
Hankinson Susan E.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a563-b
Subject(s) - metabolome , human plasma , variance (accounting) , chromatography , chemistry , metabolomics , economics , accounting
Biomarker‐based assessments of biological samples are widespread in clinical, pre‐clinical, and epidemiological investigations. Such studies require validation in three progressive domains: (i) analytical issues; (ii) inter/intra‐personal biological variation, and; (iii) correspondence with phenotype of interest. We have developed serum metabolomic profiles that can identify ad libitum fed and caloric‐restricted rats with a high degree of accuracy. These profiles are being adapted for use in human epidemiology studies, given the increased risk of disease associated with excess weight. Studies identify these markers in human plasma, and show that these data are sufficient to enable us to determine which human samples represent blinded duplicates with 100% accuracy. At least 47 of 61 metabolites tested were stable after 48 hours (“worst case”) of exposure to shipping conditions, making these markers feasible for use in national studies. The stability of some metabolites differed between individuals, suggesting the influence of some biological parameters on parameters normally considered as analytical. Despite this, overall analytical precision (mean median CV, ~ 9%)/biological variation (median CV, ~ 50–70%) ratios appear well within the bounds necessary to consider use of metabolomics markers in human clinical trials and epidemiological studies.