The dynamic range problem in the analysis of the plasma proteome

Area of Science:

• Proteomics
• Clinical Chemistry
• Biochemistry

Background:

• Analyzing the plasma proteome presents significant challenges due to the vast range of protein concentrations.
• Accurate quantification of proteins is crucial for understanding physiological and pathological states.

Purpose of the Study:

• To examine the concentration range of 18 proteins measured over one year in a clinical laboratory setting.
• To provide data on pathological extremes in protein concentrations and assess the dynamic range of clinical assays.

Main Methods:

• Longitudinal measurement of 18 plasma proteins over a year in a clinical laboratory.
• Analysis of concentration ranges from upper limits (albumin) to lower limits (thyroid-stimulating hormone - TSH).

Main Results:

• The complete measured range spanned over 10 logs of molar abundance.
• Several plasma proteins varied over 4 logs, with clinical assay detection limits proving inadequate for full range assessment.
• Prostate-specific antigen (PSA), human chorionic gonadotropin (hCG), and cardiac troponin I concentrations may vary by over 7 logs, as suggested by higher sensitivity assays.

Conclusions:

• The dynamic range of commonly measured plasma proteins likely underestimates the total proteome's concentration range.
• Clinical assay limitations necessitate the development of more sensitive methods for comprehensive plasma proteome analysis.
• Understanding extreme protein concentration variations is vital for accurate diagnostics and biomarker discovery.