Statistical analysis of variation in the human plasma proteome

Todd H. Corzett, Imola K. Fodor, Megan W. Choi, Vicki L. Walsworth, Ken W Turteltaub, Sandra L. McCutchen-Maloney, Brett A. Chromy

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number258494
JournalJournal of Biomedicine and Biotechnology
Volume2010
DOIs
StatePublished - 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Genetics
  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

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