Advancing translational research and precision medicine with targeted proteomics

Abstract

Remarkable advances in quantitative mass spectrometry have shifted the focus of proteomics from the characterization of protein expression profiles to detailed investigations on the spatial and temporal organization of the proteome. Demands for precision therapy and personalized medicine are challenged by heterogeneity in the larger population, which have led to drawbacks in biomarker performance and therapeutic efficacy. The consistent adaptation of the cellular proteome in response to distinctive signals defines a phenotype. Acquisition of quantitative multi-layered omics data on multiple individuals over defined time scales has made it possible to establish means to probe the extent to which the genome, transcriptome and environment influence the variability of the proteome in given conditions, over time. Comprehensive, reproducible datasets generated with contemporary quantitative, massively parallel, targeted proteomic approaches offer as yet untapped benefits for biomarker discovery, development, and validation. The objective of this review is to recapitulate on advances in targeted proteomics approaches for quantifying the cellular proteome and to address ways to incorporate these data towards improving present day methodologies for biomarker evaluation and precision medicine. SIGNIFICANCE: Advances in quantitative mass spectrometry have shifted the focus of proteomics from the characterization of protein expression profiles to detailed investigations on the spatial and temporal organization of the proteome. This review expounds on avenues through which targeted proteomic methodologies can be constructively implemented in translational research and precision medicine to overcome existing challenges that hinder the success of protein biomarkers in clinics, and to develop precise therapeutics for future applications.

Keywords: Biomarker; DIA; Precision medicine; Proteome; Proteotype; SWATH-MS; Targeted proteomics.