Prospective applications of ultrahigh resolution proteomics in clinical mass spectrometry

Abstract

Advances in mass spectrometry (MS)-based proteomic strategies have resulted in robust protein biomarker discovery studies often performed on high resolution accurate mass (HRAM) platforms. For successful translation of promising protein biomarkers into useful clinical tests, trans-sector networks and collaboration among stakeholders involved in the biomarker pipeline are urgently needed. Areas covered: In this perspective, literature- and empirical evidence is combined with author's opinions to discuss the progress of ultrahigh resolution MS and provide insight in its potential for validation and development of clinical tests. Expert commentary: Thus far two 'low resolution' MS strategies have been implemented in the clinic: quantification of proteins using triple quadrupole instruments and identification of unknown microorganisms using comparative analysis with spectral libraries on MALDI-TOF instruments. The rise of HRAM technology further boosts the potential of MS-based tests for detection and quantitation of disease-specific biomarkers which meet the analytical performance specifications needed for clinical assays.

Keywords: High Resolution Accurate Mass (HRAM); Mass spectrometry; clinical chemistry proteomics; instrumental development; metrological traceability; multiple reaction monitoring; parallel reaction monitoring; protein glycosylation; protein quantitation; proteoforms.