Topological proteomics: Exploring molecular networks directly in the cell

Understanding how proteins are temporally and spatially arranged to generate function is a major challenge of the post-genomic era, as existing methods for analysing protein-protein interactions seldom reveal when and where interactions occur in vivo. Here this challenge is addressed by combining three advances: a technique capable of mapping hundreds of different molecules at light microscopic resolution in a single sample; a method for selecting the most significant protein groupings by representing the resulting data as multidimensional binary vectors; and a system for imaging the distribution of these groupings in a 'toponome map'. This approach reveals new hierarchical properties of protein network organisation, in which the frequency distribution of different protein groupings obeys Zipf's law. It also provides a rapid route to distinguish new diagnostic features and therapeutic targets in human diseases, and offers a powerful way to identify the hub proteins around which networks are organized.