Advances in top-down proteomics for disease biomarker discovery

Area of Science:

• Proteomics
• Biochemistry
• Analytical Chemistry

Background:

• Top-down mass spectrometry (MS) offers direct protein identification and characterization via fragmentation.
• Certain fragmentation techniques preserve crucial protein post-translational modifications (PTMs).
• PTMs are vital in biological pathways and disease pathogenesis, making them key targets for biomarker discovery.

Purpose of the Study:

• To review separation methods, MS instrumentation, bioinformatics, and fragmentation theory for top-down MS.
• To highlight the biological significance of top-down strategies in characterizing PTMs and discovering disease biomarkers.
• To underscore the evolving role of top-down proteomics in clinical and basic research.

Main Methods:

• Detailed review of separation techniques relevant to top-down proteomics.
• Discussion of mass spectrometry instrumentation suitable for top-down analysis.
• Exploration of fragmentation mechanisms and bioinformatics tools for data interpretation.

Main Results:

• Top-down MS effectively identifies and characterizes proteins and protein networks.
• The preservation of PTMs is a key advantage for clinical applications.
• The review consolidates current knowledge on top-down strategies for PTM characterization and biomarker discovery.

Conclusions:

• Top-down mass spectrometry is a powerful tool for analyzing intact proteins and their modifications.
• Its application in clinical biochemistry is crucial for identifying novel disease biomarkers.
• Advancements in technology position top-down proteomics as a vital strategy in modern biological and clinical research.