Advances in discovery proteomics have made it possible to map the protein contents of cells to saturation, at least at the resolution of expressed loci. Massively parallel targeting techniques such as Swath/DIA mass spectrometry now support the identification and quantification of thousands of proteins from a sample at a high degree of reproducibility. To gain new biological or clinical insights, to date, the thus quantified proteins have been largely treated as independent entities. However, proteins generally function in context with other biomolecules in the form of macromolecular assemblies. To understand how the proteome as a whole controls, coordinates and catalyzes most biochemical functions of a cell, it is therefore essential to also determine its spatial and temporal organization. We refer to the acute state of a proteome in terms of protein composition and the organization of proteins into modules or complexes as the proteotype. The determination of proteotypes, particularly the organization of proteins into modules and complexes, is therefore an important challenge facing the field of proteomics.
In this presentation, we will discuss emerging computational and mass spectrometric techniques to determine the organization of the proteome and to extract functional information from the results. The ultimate goal of this work is to reach a comprehensive understanding of how the proteotype, considered as a complex system, reacts to genetic or external perturbations and thus determines cellular and organismic phenotypes.