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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

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    Issue Date
    2004
    Author
    Paolucci, Ugo
    Vigneau-Callahan, Karen E.
    Shi, Honglian
    Matson, Wayne R.
    Kristal, Bruce S.
    Publisher
    Mary Ann Liebert, Inc.
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
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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.
    Description
    This is the publisher's version, also available electronically from: http://online.liebertpub.com/doi/pdfplus/10.1089/omi.2004.8.209
    URI
    http://hdl.handle.net/1808/9575
    DOI
    https://doi.org/10.1089/omi.2004.8.209
    Collections
    • Pharmacy Scholarly Works [288]
    Citation
    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.

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    KU Libraries
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    785-864-8983

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    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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