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The functional analysis of genes provides relevant information to understand cellular function. Further, the mapping of genetic interactions sheds light on how genes act in the emergence of cellular complexity. Here, we present the most extensive genetic interaction and morphological profiling screen in a metazoan cell to date. We profiled 680 0…

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Heigwer et al., Cell systems 2022

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Heigwer et al., 2023, A global genetic interaction network by single-cell imaging and machine learning, Cell Systems

Abstract

Cellular and organismal phenotypes are controlled by complex gene regulatory networks. However, reference maps of gene function are still scarce across different organisms. Here, we generated synthetic genetic interaction and cell morphology profiles of more than 6,800 genes in cultured Drosophila cells. The resulting map of genetic interactions was used for machine learning-based gene function discovery, assigning functions to genes in 47 modules. Furthermore, we devised Cytoclass as a method to dissect genetic interactions for discrete cell states at the single-cell resolution. This approach identified an interaction of Cdk2 and the Cop9 signalosome complex, triggering senescence-associated secretory phenotypes and immunogenic conversion in hemocytic cells. Together, our data constitute a genome-scale resource of functional gene profiles to uncover the mechanisms underlying genetic interactions and their plasticity at the single-cell level.

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Should you encounter any issues or have any questions please contact Florian Heigwer [email protected] or Michael Boutros [email protected].

Raw sequencing read data are deposit at ENA under the Study ID: PRJEB48815

Raw & processeed scRNA-seq matrices as well as Raw & processed well-average interaction feature matrices are availanble at : 10.6084/m9.figshare.14192783

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The functional analysis of genes provides relevant information to understand cellular function. Further, the mapping of genetic interactions sheds light on how genes act in the emergence of cellular complexity. Here, we present the most extensive genetic interaction and morphological profiling screen in a metazoan cell to date. We profiled 680 0…

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