Relevant phosphoproteomic and mass spectrometry: approaches useful in clinical research

Understanding the functions of phosphorylated proteins thus requires one to study proteomes as linked-systems rather than collections of individual protein molecules. Indeed, the interacting proteome or protein-network knowledge has recently received much attention, as network-systems (signalling pathways) are effective snapshots in time, of the proteome as a whole. MS approaches are clearly essential, in spite of the difficulties of some low abundance proteins for future clinical advances.Clinical proteomics-MS has come a long way in the past decade in terms of technology/platform development, protein chemistry, and together with bioinformatics and other OMICS tools to identify molecular signatures of diseases based on protein pathways and signalling cascades. Hence, there is great promise for disease diagnosis, prognosis, and prediction of therapeutic outcome on an individualized basis. However, and as a general rule, without correct study design, strategy and implementation of robust analytical methodologies, the efforts, efficiency and expectations to make biomarkers (especially phosphorylated kinases) a useful reality in the near future, can easily be hampered.Proteomics and phosphoproteomics clinical research studies imply the comprehensive analysis of the proteins which are expressed in cells or tissues, and can be employed at different stages (e.g. healthy vs. disease). Therefore, comparative proteomics can distinguish small, but relevant changes in protein modifications in their structure -post-translational modifications (PTMs)- at a depth of several thousand proteins to facilitate drug target identification.Chemical and Biochemical proteomics can be used to identify drug-target interactions and subsequently analyze drug specificity and selectivity. Furthermore, phosphoproteomic approaches can be exploited to monitor changes in phosphorylation events in order to characterize drug actions on cell signalling pathways and/or signalling cascades. In addition,