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Mapping the perturbome network of cellular perturbations

Author

Listed:
  • Michael Caldera

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Felix Müller

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Isabel Kaltenbrunner

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Marco P. Licciardello

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
    The Institute of Cancer Research)

  • Charles-Hugues Lardeau

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
    AstraZeneca)

  • Stefan Kubicek

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Jörg Menche

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

Abstract

Drug combinations provide effective treatments for diverse diseases, but also represent a major cause of adverse reactions. Currently there is no systematic understanding of how the complex cellular perturbations induced by different drugs influence each other. Here, we introduce a mathematical framework for classifying any interaction between perturbations with high-dimensional effects into 12 interaction types. We apply our framework to a large-scale imaging screen of cell morphology changes induced by diverse drugs and their combination, resulting in a perturbome network of 242 drugs and 1832 interactions. Our analysis of the chemical and biological features of the drugs reveals distinct molecular fingerprints for each interaction type. We find a direct link between drug similarities on the cell morphology level and the distance of their respective protein targets within the cellular interactome of molecular interactions. The interactome distance is also predictive for different types of drug interactions.

Suggested Citation

  • Michael Caldera & Felix Müller & Isabel Kaltenbrunner & Marco P. Licciardello & Charles-Hugues Lardeau & Stefan Kubicek & Jörg Menche, 2019. "Mapping the perturbome network of cellular perturbations," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13058-9
    DOI: 10.1038/s41467-019-13058-9
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    Cited by:

    1. Pisanu Buphamalai & Tomislav Kokotovic & Vanja Nagy & Jörg Menche, 2021. "Network analysis reveals rare disease signatures across multiple levels of biological organization," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

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