Abstract

The genetic basis underlying phenotypes is often interactions with large effects on many phenotypes. Moreover, interactions between genetic variants have been proposed as one possible explanation for a “missing heritability” in genome-wide association studies. We devised RNAi-based experiments to explore cellular processes based on their genetic interaction profiles. Multiparametric imaging of Drosophila cells and robust statistical modelling were used to identify combinatorial RNAi phenotypes. Such experiments showed distinct genetic interactions based on different cellular phenotypes, generating networks of interacting genes that are significantly enriched in known genetic and protein-protein interactions. Phenotype-specific interactions provided an additional layer of information which can be used to predict the flow of information. I will discuss our progress in mapping the interaction landscape of larger gene sets and how to capture differential genetic interactions base d on multiple phenotypes by fluorescence imaging.