A map of directional genetic interactions in a metazoan cell

  1. Bernd Fischer
  2. Thomas Sandmann
  3. Thomas Horn
  4. Maximilian Billmann
  5. Varun Chaudhary
  6. Wolfgang Huber
  7. Michael Boutros  Is a corresponding author
  1. European Molecular Biology Laboratory, Germany
  2. German Cancer Research Center, Germany

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.

Article and author information

Author details

  1. Bernd Fischer

    Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Thomas Sandmann

    Division of Signaling and Functional Genomics, German Cancer Research Center, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Thomas Horn

    Division of Signaling and Functional Genomics, German Cancer Research Center, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Maximilian Billmann

    Division of Signaling and Functional Genomics, German Cancer Research Center, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Varun Chaudhary

    Division of Signaling and Functional Genomics, German Cancer Research Center, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Wolfgang Huber

    Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Michael Boutros

    Division of Signalling and Functional Genomics, German Cancer Research Center, Heidelberg, Germany
    For correspondence
    m.boutros@dkfz.de
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Christopher K Glass, University of California, San Diego, United States

Version history

  1. Received: November 3, 2014
  2. Accepted: February 28, 2015
  3. Accepted Manuscript published: March 6, 2015 (version 1)
  4. Version of Record published: April 2, 2015 (version 2)

Copyright

© 2015, Fischer et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Bernd Fischer
  2. Thomas Sandmann
  3. Thomas Horn
  4. Maximilian Billmann
  5. Varun Chaudhary
  6. Wolfgang Huber
  7. Michael Boutros
(2015)
A map of directional genetic interactions in a metazoan cell
eLife 4:e05464.
https://doi.org/10.7554/eLife.05464

Share this article

https://doi.org/10.7554/eLife.05464

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