Quantitative protein biomarker panels: a path to improved clinical practice through proteomics

Abstract

The utilisation of protein biomarker panels, rather than individual protein biomarkers, offers a more comprehensive representation of human physiology. It thus has the potential to improve diagnosis, prognosis and the differentiation of responders from nonresponders in the context of precision medicine. Although several proteomic techniques exist for measuring biomarker panels, the integration of proteomics into clinical practice has been limited. In this Commentary, we highlight the significance of quantitative protein biomarker panels in clinical medicine and outline the challenges that must be addressed in order to identify the most promising panels and implement them in clinical routines to realise their medical potential. Furthermore, we argue that the absolute quantification of protein panels through targeted mass spectrometric assays remains the most promising technology for translating proteomics into routine clinical applications due to its high flexibility, low sample costs, independence from affinity reagents and low entry barriers for its integration into existing laboratory workflows.

Figure 1. Translational multi‐marker protein panels: Current medical needs, challenges, and advancements

1. A, B

   Proteomics signatures and protein panel assays can fill diagnostic, prognostic and predictive gaps and improve performance compared to individual biomarkers.

2. C

   Analysis of proteomic panels together with metadata requires advanced yet streamlined data analysis pipelines and a simple scoring output for clinical interpretation. Multivariate analysis requires large cohorts to identify important protein features and build robust models. To gain sufficient data and produce reproducible protein panels, high comparability between sites and the method used to quantify markers, as well as absolute quantification are important.

3. D

   Recent advances in proteomics with respect to throughput, automation, instruments and proteomics data analysis software, as well as tools to access and statistically analyse data, have facilitated the discovery of protein signatures of clinical value. Targeted mass spectrometers equipped in routine laboratories can translate these protein signatures into clinical assays. Panels or combinations of the biomarkers can be repurposed, for example in the context of infectious diseases.