We developed methods for detecting direct (binary) interactions between pairs of proteins, based on the complementation of luciferase enzymes (“split-luciferase”). We use these methods for high-throughput PPIs mapping in human cells (HEK293T). Our pipelines provide systematic, semi-quantitative and comparative PPIs maps. We are using the human ORFeome library, a collection of 17,000 human cDNAs, to gather pathway-dedicated sub-collections, i.e. an innate immunity-oriented library or a Ubiquitin Proteasome System library. The IRI laboratory focuses on virus/host PPIs, mainly studying respiratory and emerging viruses with the goal to identify molecular requisites of viral adaptation to human. We are open to collaborations for binary PPIs screening of our currently available libraries, for generating new human-proteome sub-libraries with any type of protein partners, should they be from a pathogen or not. Application of our PPIs screening pipeline to other organisms can be envisaged provided that orfeome of studied species are generated.