A map of directional genetic interactions in a metazoan cell

Berad Fischer, Thomas Sandmann, Thomas Horn, Maximilian Billmann, Vanin Chaudhary, Wolfgang Huber, Michael Boutros

    Research output: Contribution to journalArticle

    47 Scopus citations

    Abstract

    Gene-gene interactions shape complex phenotypes and modify the effects of mutations during development and disease. The effects of statistical gene-gene interactions on phenotypes have been used to assign genes to functional modules. However, directional, epistatic interactions, which reflect regulatory relationships between genes, have been challenging to map at large-scale. Here, we used combinatorial RNA interference and automated single-cell phenotyping to generate a large genetic interaction map for 21 phenotypic features of Drosophila cells. We devised a method that combines genetic interactions on multiple phenotypes to reveal directional relationships. This network reconstructed the sequence of protein activities in mitosis. Moreover, it revealed that the Ras pathway interacts with the SWI/SNF chromatin-remodelling complex, an interaction that we show is conserved in human cancer cells. Our study presents a powerful approach for reconstructing directional regulatory networks and provides a resource for the interpretation of functional consequences of genetic alterations.

    Original languageEnglish (US)
    Article numbere05464
    JournaleLife
    Volume2015
    Issue number4
    DOIs
    StatePublished - Mar 6 2015

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Immunology and Microbiology(all)
    • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Fischer, B., Sandmann, T., Horn, T., Billmann, M., Chaudhary, V., Huber, W., & Boutros, M. (2015). A map of directional genetic interactions in a metazoan cell. eLife, 2015(4), [e05464]. https://doi.org/10.7554/eLife.05464