Mass spectrometry-based plasma proteomics: state of the art and future outlook

Abstract

Mass spectrometry-based plasma proteomics is a field where intense research has been performed during the last decade. Being closely linked to biomarker discovery, the field has received a fair amount of criticism, mostly due to the low number of novel biomarkers reaching the clinic. However, plasma proteomics is under gradual development with improvements on fractionation methods, mass spectrometry instrumentation and analytical approaches. These recent developments have contributed to the revival of plasma proteomics. The goal of this review is to summarize these advances, focusing in particular on fractionation methods, both for targeted and global mass spectrometry-based plasma analysis.

Keywords::

• biomarkers
• fractionation
• high abundance protein depletion
• mass spectrometry
• MRM
• plasma
• proteomics
• quantitation
• serum
• SRM
• SWATH

Financial & competing interests disclosure

The authors were supported by Swedish cancer society (Cancerfonden), Swedish Research Council (Vetenskapsrådet) and FP7 EU Project GlycoHit. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Global discovery of biomarkers in plasma is still challenging in larger cohorts.

• There is no consensus in the field regarding the optimal fractionation method to achieve high proteome coverage and/or high sample throughput.

• Developments within chromatography and mass spectrometry instrumentation have improved the performance of both global and targeted analyses.

• Fractionation is needed for improved analytical depth also in targeted multiple reaction monitoring/selected reaction monitoring-based approaches.