Towards a proteome-scale map of the human protein-protein interaction network

Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes(1,2) and then expanding to the scale of the proteome(3-7). Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties(8,9), suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of similar to 8,100 currently available Gateway-cloned open reading frames and detected similar to 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of similar to 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by similar to 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.