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Kinetic Visualization of Single-Cell Interspecies Bacterial Interactions

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A global genetic interaction network by single-cell imaging and machine learning.

Florian Heigwer¹, Christian Scheeder², Josephine Bageritz³

¹German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics and Department of Cell and Molecular Biology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; Department of Life Sciences and Engineering, University of Applied Sciences Bingen, Bingen am Rhein, Germany.

|April 28, 2023

Summary

This summary is machine-generated.

Researchers mapped gene function in Drosophila cells, revealing 47 gene modules and identifying a Cdk2-Cop9 interaction linked to cell senescence and immune responses. This provides a valuable resource for understanding gene interactions.

Keywords:

Drosophila genome gene-function relationship genetic epistasis machine learning phenotypic profiling single-cell phenotyping synthetic genetic interaction

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Area of Science:

Genetics and Genomics
Cell Biology
Systems Biology

Background:

Gene regulatory networks control cellular and organismal phenotypes.
Comprehensive gene function maps are lacking across diverse organisms.
Understanding genetic interactions is crucial for deciphering biological complexity.

Purpose of the Study:

To generate a genome-scale resource of functional gene profiles in Drosophila.
To utilize machine learning for gene function discovery based on genetic interactions.
To develop a method for dissecting genetic interactions at single-cell resolution.

Main Methods:

Generated synthetic genetic interaction and cell morphology profiles for over 6,800 Drosophila genes.
Applied machine learning to the genetic interaction map for gene function assignment into 47 modules.
Developed Cytoclass, a single-cell resolution method to analyze genetic interactions in discrete cell states.

Main Results:

Created a comprehensive map of genetic interactions and cell morphology profiles.
Identified functions for genes within 47 distinct modules using machine learning.
Discovered a Cdk2 and Cop9 signalosome complex interaction impacting hemocytic cell senescence and immune phenotypes.

Conclusions:

The study provides a genome-scale functional gene resource for Drosophila.
The findings elucidate mechanisms of genetic interactions and their plasticity.
Cytoclass enables high-resolution dissection of gene interactions in specific cellular contexts.