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Development of Biomarkers Based on Diet-Dependent Metabolic Serotypes: Concerns and Approaches for Cohort and Gender Issues in Serum Metabolome Studies
Paolucci, Ugo Vigneau-Callahan, Karen E. Shi, Honglian Matson, Wayne R. Kristal, Bruce S.
Paolucci, Ugo
Vigneau-Callahan, Karen E.
Shi, Honglian
Matson, Wayne R.
Kristal, Bruce S.
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Abstract
Mathematical models that reflect the effects of dietary restriction (DR) on the sera
metabolome may have utility in understanding the mechanisms of DR and in applying this
knowledge to human epidemiological studies. Previous studies demonstrated both the feasibility
of identifying biomarkers through metabolome analysis and the validity of our approach
in independent cohorts of 6-month-oId male and female ad libitum fed or DR rats.
Cross-cohort studies showed that cohort-specific effects distorted the dataset The present
study extends these observations across the entire sample set, thereby validating our markers
independently of specific cohorts. Metabolites originally identified in males were examined
in females and vice-versa. DR's effect on the metabolom e is partially gender-specific
and is modulated by environmental factors. DR reduces inter-gender differences in the
metabolome. Univariate statistical methods showed that 56/93 metabolites in the female samples
and 39/93 metabolites in the male samples were significantly altered (using our previous
cut-off criteria of p ^ 0.2) by DR. The metabolites modulated by DR present a wide
spectrum of concentration, redox reactivity and hydrophilicity, suggesting that our serotype
is broadly representative of the metabolome and that DR has broad effects on the
metabolome. These studies, coupled with those in the preceding and following reports, also
highlight the utility for consideration of the metabolome as a network of metabolites using
appropriate data analysis approaches. The inter-cohort and inter-gender differences addressed
herein suggest potential cautions, and potential approaches, for identification of multivariate
biomarker profiles that reflect changes in physiological status, such as a metabolism
that predisposes to increased risk of neoplasia.
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This is the publisher's version, also available electronically from: http://online.liebertpub.com/doi/pdfplus/10.1089/omi.2004.8.209
Date
2004
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Mary Ann Liebert, Inc.
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Paolucci U, Vigneau-Callahan KE, Shi H, Shestopalov AI, Milbury PE, Matson WR, and Kristal BS. Development of biomarkers based on diet-dependent metabolic serotypes: concerns and approaches for cohort and gender issues in serum metabolome studies. OMICS J Integr Biol 8 (3): 209-220; 2004.