Targeted Proteomics in Translational and Clinical Studies

This chapter provides a concise overview on the methods and applications of targeted proteomics in the context of translational and clinical studies. Mass spectrometry-based targeted proteomics has emerged as a promising technique for protein and peptide quan‐ tification, presenting a great potential for clinical applications. While significant amount of discovery works have been carried out in both genomics and proteomics for an assort‐ ment of diseases, it has been challenging in further characterizing individual protein tar‐ gets for their biological significance and clinical value due to the lack of effective and “universal” techniques. The development of targeted proteomics approach opened a unique avenue to bridge the discovery-based genomics and proteomics with candidatebased protein analysis, which is clinically highly relevant. Targeted proteomics analysis has been implemented on a variety of instrument platforms, and applied for a wide range of studies, from blood biomarker detection to pathway-driven mechanistic investigations, with the triple quadrupole-based selected reaction monitoring (SRM) technique being the most widely used method. With a right combination of calibration approach, internal standards, and sample preparation strategies, mass spectrometry-based targeted analysis has proven to be of inter-laboratory reproducibility and sensitivity in analyzing many clinical specimens. More recently, the advent of mass spectrometry with high frequencies and resolutions yielded the data independent acquisition (DIA) techniques, such as se‐ quential window acquisition of all theoretical fragment ion spectra (SWATH). The un‐ biased nature of DIA methods would enable a wider analytical scope and a greater robustness in targeted analysis, representing a paradigm shift in targeted proteomics.