Proteomics turns functional

Proteomics is acquiring a pivotal role in the comprehensive understanding of human biology. Biochemical processes involved in complex diseases, such as neurodegenerative diseases, diabetes and cancer, can be identified by combining proteomics analysis and bioinformatics tools. In the last ten years, the main output of differential proteomics investigations evolved from long lists of proteins to the generation of new hypotheses and their functional verification. The Journal of Proteomics participated to this progress, reporting more and more biologically-oriented papers with functional interpretation of proteomics data. This change in the field was due to both technological development and novel strategies in exploiting the deep characterization of proteomes. In this review, we explore several approaches that allow proteomics to turn functional. In particular, systems biology tools for data analysis are now routinely used to interpret results, thus defining the biological meaning of differentially abundant proteins. Moreover, by considering the importance of protein-protein interactions and the composition of macromolecular complexes, interactomics is complementing the information given by differential quantitative proteomics. Eventually, terminomics is unveiling new functions for cleaved proteoforms, by analyzing the effect of proteolysis globally. Significance: Proteomics is rapidly evolving not only technologically but also strategically. The correct interpretation of proteomics data can reveal new functions of proteins in several biological backgrounds. Systems biology tools allow researchers to formulate new hypotheses to be further functionally tested. Interactomics is shedding new light on protein complexes truly involved in biochemical pathways and how their alteration can lead to dysfunctionality (in disease pathogenesis, for example). Terminomics is revealing the function of new discovered proteoforms and attributing a novel role to proteolysis. This review would provide the biologist important insights into current applications of several proteomic approaches that could offer new strategies to investigate biological systems.