Clinical translation of MS-based, quantitative plasma proteomics: status, challenges, requirements, and potential

ABSTRACT

Introduction: Aided by the advent of advanced mass spectrometry (MS)-based technologies and methodologies, quantitative proteomics has emerged as a viable technique to capture meaningful data for candidate biomarker evaluation. To aid clinical translation, these methods generally utilize a bottom-up strategy with isotopically labeled standards and a targeted form of MS measurement.

Areas covered: This article reviews the status, challenges, requirements, and potential of translating current, MS-based methods to the clinical laboratory. The described methods are discussed and contrasted within a fit-for-purpose approach, while different resources for quality control, quantitative analysis, and data interpretation are additionally provided.

Expert commentary: Although great strides have been made over the past five years in developing reliable quantitative assays for plasma protein biomarkers, it is crucial for investigators to have an understanding of the clinical validation process, a major roadblock in translational research. Continued progress in method design and validation of protein assays is necessary to ultimately achieve widespread adoption and regulatory approval.

KEYWORDS:

• Biomarker
• clinic
• disease
• MRM
• MS
• PRM
• protein
• proteomics
• quantification
• translation

Declaration of interest

Authors A Percy, T Agreste, and M Duffy are employed with Cambridge Isotope Laboratories, which has commercialized one of the standardization products - ProteusQC^™ - discussed. S Pennington is founder of the UCD spinout biomarker company Atturos. D Holmes has given remunerated scientific talks for Immunodiagnostic Services and has sat on two single-day advisory boards for EMD Serono and Pfizer. N Anderson is the chairman, CEO, and founder of SISCAPA Assay Technologies, Inc. The authors have no other 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 apart from those disclosed.

Additional information

Funding

Author S Pennington would like to acknowledge financial support from the Health Research Board (HRB) (HRA_POR/2011/125, POR/2015/1284), St Luke’s Institute of Cancer Research, and the European Commission under the EU FP7 project ‘MIAMI’. Additional support is provided by Science Foundation Ireland that funds the MS instrumentation at the UCD Conway Institute, which is supported by the Programme for Research in Third level Institutions, as administered by Higher Education Authority of Ireland.