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Utilizing human blood plasma for proteomic biomarker discovery.
Jon M Jacobs1, Joshua N Adkins, Wei-Jun Qian
1Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, PO Box 999, Richland, WA 99352, USA.
Journal of Proteome Research
|August 9, 2005
Summary
Discovering proteomic biomarkers in human plasma is challenging due to extreme protein concentration differences. Current mass spectrometry (MS) methods struggle with low-abundance biomarker detection, necessitating advanced techniques.
Area of Science:
- Proteomics
- Biomarker Discovery
- Mass Spectrometry
Background:
- Human plasma contains a vast dynamic range of proteins (exceeding 10^10).
- Many potential biomarkers exist at very low protein abundances.
- Current mass spectrometry (MS) techniques have limited dynamic range, hindering direct detection of low-abundance biomarkers in plasma.
Purpose of the Study:
- To discuss current experimental methodologies and strategies for enhancing proteomic analysis of human plasma.
- To highlight approaches for increasing the number of detectable proteins in plasma for biomarker discovery.
Main Methods:
- Utilizing various separation techniques (e.g., reversed-phase gradient liquid chromatography).
- Implementing protein depletion and enrichment strategies.
- Leveraging recent improvements in mass spectrometry (MS) capabilities.
Main Results:
- Measurable improvements (10-100 fold) in detecting and identifying lower abundance proteins have been achieved.
- Current MS analyses combined with separations offer a dynamic range up to approximately 10^6.
- Despite advancements, further improvements are required for detecting very low-level biomarkers.
Conclusions:
- Advanced depletion and enrichment techniques are crucial for overcoming dynamic range limitations in plasma proteomics.
- Improved pre-MS separations at both protein and peptide levels are essential for extending the dynamic range of proteomic analysis.
- Continued innovation is needed to enable robust discovery of low-abundance candidate biomarkers in human plasma.