Clinically Relevant Post-Translational Modification Analyses—Maturing Workflows and Bioinformatics Tools

Abstract

Post-translational modifications (PTMs) can occur soon after translation or at any stage in the lifecycle of a given protein, and they may help regulate protein folding, stability, cellular localisation, activity, or the interactions proteins have with other proteins or biomolecular species. PTMs are crucial to our functional understanding of biology, and new quantitative mass spectrometry (MS) and bioinformatics workflows are maturing both in labelled multiplexed and label-free techniques, offering increasing coverage and new opportunities to study human health and disease. Techniques such as Data Independent Acquisition (DIA) are emerging as promising approaches due to their re-mining capability. Many bioinformatics tools have been developed to support the analysis of PTMs by mass spectrometry, from prediction and identifying PTM site assignment, open searches enabling better mining of unassigned mass spectra—many of which likely harbour PTMs—through to understanding PTM associations and interactions. The remaining challenge lies in extracting functional information from clinically relevant PTM studies. This review focuses on canvassing the options and progress of PTM analysis for large quantitative studies, from choosing the platform, through to data analysis, with an emphasis on clinically relevant samples such as plasma and other body fluids, and well-established tools and options for data interpretation.

Post-Translational Modification-Dependent Activity of Matrix Metalloproteinases

“…Advances in MS-based methods including multiplexed chemical labeling, novel label-free quantification strategies, improvement in PTM enrichment, more robust PTM analysis workflows and streamlined bioinformatics strategies will contribute to reliable identification and quantification of high numbers of PTMs [126,127]. The remaining challenge lies in defining the functional role of the physiologically relevant PTMs to understand PTM-dependent activity of MMPs in complex biological systems [128].…”

Data-independent acquisition mass spectrometry (DIA-MS) for proteomic applications in oncology

“…This review will focus on DIA-MS applications in tissue and cell line analysis, and readers who are interested in the use of this technology in liquid biopsies and plasma proteomics are referred to these excellent reviews on the topic. [14][15][16] We further present the latest innovations in DIA-MS that will push the boundaries of this technology and accelerate its implementation in precision cancer medicine.…”

Proteomic Investigations of In Vitro and In Vivo Models of Periodontal Disease

“…Of general interest, modification of proteins by phosphorylation has given rise to the wide spread analysis of phosphoproteomics and signaling cascades. Other modifications such as oxidation and glutathionylation have been of interest in the field of oral models of periodontal disease, although many other modification have been explored in other areas …”