Plasma Proteome Profiling to detect and avoid sample-related biases in biomarker studies

Area of Science:

• Proteomics
• Biomarker Discovery
• Clinical Chemistry

Background:

• Plasma and serum are vital for health assessment, but few protein biomarkers reach clinical use.
• Mass spectrometry (MS)-based proteomics offers precise quantification of the plasma proteome.
• Challenges remain in distinguishing true biomarkers from sample handling artifacts.

Purpose of the Study:

• To develop quality marker panels for assessing plasma sample integrity.
• To differentiate genuine biomarker candidates from processing-related artifacts.
• To provide guidelines and resources for reliable biomarker discovery.

Main Methods:

• Acquired deep reference proteomes (> 6,000 proteins) from erythrocytes, platelets, plasma, and whole blood.
• Compared serum and plasma proteomes using spike-in experiments.
• Conducted a comprehensive literature survey of reported biomarker candidates.

Main Results:

• Identified sample quality-associated proteins, many previously reported as biomarker candidates.
• Demonstrated the utility of Plasma Proteome Profiling for quality control.
• Highlighted the potential for sample handling to introduce bias.

Conclusions:

• Plasma Proteome Profiling effectively defines quality marker panels for sample assessment.
• Established guidelines and an online resource can prevent misinterpretation of biomarker candidates.
• This approach enhances the reliability of biomarker discovery in clinical studies.