Final Report Summary - SYNGENE (Global Mapping of Synthetic Genetic Interactions in Drosophila)
Gene-gene interactions shape complex phenotypes and modify the effects of mutations during development and disease. Genes display epistatic (genetic) interactions, whereby the presence of one genetic variant can mask, alleviate or amplify the phenotypic effect of other variants. We used combinatorial RNA interference and automated, single-cell phenotyping to generate the largest systematic genetic interaction map across many different phenotypic features of Drosophila cells. We devised methods that combine data on multiple phenotypes to reveal directional relationships, treatment and time dependent genetic interactions and report the largest network of functional relationships of genes in metazoan cells covering several thousand genes. This network could reconstruct diverse functional complexes and the studies of directed, differential and time-dependent interactions discovered a number of before uncharacterized modifiers of known cellular processes. Our work presents a powerful approach for reconstructing functional regulatory networks and provides a resource for the interpretation of functional consequences of genomic alterations in disease.