Statistical Analysis of Variation in the Human Plasma Proteome

Journal Article · Thu Dec 31 23:00:00 EST 2009 · Journal of Biomedicine and Biotechnology

DOI:https://doi.org/10.1155/2010/258494· OSTI ID:1198317

Corzett, Todd H. ^[1]; Fodor, Imola K. ^[2]; Choi, Megan W. ^[1]; Walsworth, Vicki L. ^[1]; Turteltaub, Kenneth W. ^[1]; McCutchen-Maloney, Sandra L. ^[1]; Chromy, Brett A. ^[1]

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1. Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA 94550, USA
2. Department of Biostatistics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA

Quantifying the variation in the human plasma proteome is an essential prerequisite for disease-specific biomarker detection. We report here on the longitudinal and individual variation in human plasma characterized by two-dimensional difference gel electrophoresis (2-D DIGE) using plasma samples from eleven healthy subjects collected three times over a two week period. Fixed-effects modeling was used to remove dye and gel variability. Mixed-effects modeling was then used to quantitate the sources of proteomic variation. The subject-to-subject variation represented the largest variance component, while the time-within-subject variation was comparable to the experimental variation found in a previous technical variability study where one human plasma sample was processed eight times in parallel and each was then analyzed by 2-D DIGE in triplicate. Here, 21 protein spots had larger than 50% CV, suggesting that these proteins may not be appropriate as biomarkers and should be carefully scrutinized in future studies. Seventy-eight protein spots showing differential protein levels between different individuals or individual collections were identified by mass spectrometry and further characterized using hierarchical clustering. The results present a first step toward understanding the complexity of longitudinal and individual variation in the human plasma proteome, and provide a baseline for improved biomarker discovery.

• Sponsoring Organization: USDOE
• Grant/Contract Number: AC52-07NA27344
• OSTI ID: 1198317
• Journal Information: Journal of Biomedicine and Biotechnology, Journal Name: Journal of Biomedicine and Biotechnology Vol. 2010; ISSN 1110-7243
• Publisher: Hindawi Publishing Corporation
• Country of Publication: Country unknown/Code not available
• Language: English