Applications of targeted proteomics in systems biology and translational medicine

Abstract

Biological systems are composed of numerous components of which proteins are of particularly high functional significance. Network models are useful abstractions for studying these components in context. Network representations display molecules as nodes and their interactions as edges. Because they are difficult to directly measure, functional edges are frequently inferred from suitably structured datasets consisting of the accurate and consistent quantification of network nodes under a multitude of perturbed conditions. For the precise quantification of a finite list of proteins across a wide range of samples, targeted proteomics exemplified by selected/multiple reaction monitoring (SRM, MRM) mass spectrometry has proven useful and has been applied to a variety of questions in systems biology and clinical studies. Here, we survey the literature of studies using SRM‐MS in systems biology and clinical proteomics. Systems biology studies frequently examine fundamental questions in network biology, whereas clinical studies frequently focus on biomarker discovery and validation in a variety of diseases including cardiovascular disease and cancer. Targeted proteomics promises to advance our understanding of biological networks and the phenotypic significance of specific network states and to advance biomarkers into clinical use.

Human SRMAtlas: A Resource of Targeted Assays to Quantify the Complete Human Proteome

“…Recently, we developed SRM assays for Saccharomyces cerevisiae (Picotti et al, 2009; Picotti et al, 2013), Streptococcus pyogenes (Karlsson et al, 2012) and Mycobacterium tuberculosis (Schubert et al, 2013) proteomes and successfully applied these assays to a wide range of protein studies in the respective species (Ebhardt et al, 2015; Picotti and Aebersold, 2012). We and several other laboratories have also developed SRM assays for human proteins, typically for a small number of proteins in the context of a specific biological study.…”

Peroxidatic cysteine residue of peroxiredoxin 2 separated from human red blood cells treated by tert-butyl hydroperoxide is hyperoxidized into sulfinic and sulfonic acids

“…This is a relative quantification, and differences in ion intensities do not reflect those in the molecular number of the three species of Prx2 37-61 due to various biases such as different ionization efficiency among them. Absolute quantities need to be measured using selected ion monitoring (SRM) [33,34]; however, we cannot apply SRM to the three species of Prx2 37-61 because of technical difficulties associated with the synthesis and usage of these peptides. We now consider SIM to be the most suitable for quantifying the three species of Prx2 37-61 .…”

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

“…As a whole, methodologies for biomarker analysis and biochemical pathway interrogation are beginning to be developed under a fit-for-purpose approach with the clinical endpoint in mind [111]. For a collection of methods, standard curves with QCs have been instituted to measure system and curve performance.…”