Mapping the perturbome network of cellular perturbations. Academic Article uri icon

Overview

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.

publication date

  • November 13, 2019

Research

keywords

  • Cells
  • Drug Interactions
  • Protein Interaction Mapping

Identity

PubMed Central ID

  • PMC6853941

Scopus Document Identifier

  • 85074958427

Digital Object Identifier (DOI)

  • 10.1016/j.cels.2015.10.001

PubMed ID

  • 31723137

Additional Document Info

volume

  • 10

issue

  • 1