Statistical analysis of variation in the human plasma proteome

Area of Science:

• Biochemistry
• Proteomics
• Human Physiology

Background:

• Accurate quantification of human plasma proteome variation is crucial for identifying reliable disease biomarkers.
• Understanding both individual and longitudinal variations is essential for robust biomarker discovery.

Purpose of the Study:

• To quantify the longitudinal and individual variation in the human plasma proteome.
• To identify potential protein candidates for biomarkers and assess their suitability.

Main Methods:

• Two-dimensional difference gel electrophoresis (2-D DIGE) was employed on plasma samples from eleven healthy subjects over two weeks.
• Fixed-effects and mixed-effects modeling were utilized to analyze and quantify sources of proteomic variation.
• Mass spectrometry and hierarchical clustering were used for protein identification and characterization.

Main Results:

• Subject-to-subject variation was the largest component of proteomic variation.
• Time-within-subject variation was comparable to experimental technical variation.
• Twenty-one protein spots exhibited high coefficient of variation (>50%), suggesting caution for biomarker use.
• Seventy-eight differentially expressed protein spots were identified between individuals or collections.

Conclusions:

• This study provides a foundational understanding of human plasma proteome complexity in terms of individual and longitudinal variation.
• The findings offer a baseline for future biomarker discovery efforts, highlighting proteins that require careful scrutiny.