2. Academic Validation
  3. Spatially resolved subcellular protein-protein interactomics in drug-perturbed lung-cancer cultures and tissues

Spatially resolved subcellular protein-protein interactomics in drug-perturbed lung-cancer cultures and tissues

  • Nat Biomed Eng. 2024 Oct 30. doi: 10.1038/s41551-024-01271-x.
Shuangyi Cai # 1,  Thomas Hu # 1 2,  Abhijeet Venkataraman 1 3,  Felix G Rivera Moctezuma 4 5,  Efe Ozturk 1 2 3,  Nicholas Zhang 1 5,  Mingshuang Wang 1 3,  Tatenda Zvidzai 1,  Sandip Das 1,  Adithya Pillai 1,  Frank Schneider 6 7,  Suresh S Ramalingam 7 8,  You-Take Oh 7 8,  Shi-Yong Sun 7 8,  Ahmet F Coskun 9 10 11
Affiliations

Affiliations

  • 1 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
  • 2 School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
  • 3 Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
  • 4 Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
  • 5 Interdisciplinary Bioengineering Graduate Program, Georgia Institute of Technology, Atlanta, GA, USA.
  • 6 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
  • 7 Winship Cancer Institute of Emory University, Atlanta, GA, USA.
  • 8 Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
  • 9 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA. ahmet.coskun@bme.gatech.edu.
  • 10 Interdisciplinary Bioengineering Graduate Program, Georgia Institute of Technology, Atlanta, GA, USA. ahmet.coskun@bme.gatech.edu.
  • 11 Winship Cancer Institute of Emory University, Atlanta, GA, USA. ahmet.coskun@bme.gatech.edu.
  • # Contributed equally.
PMID: 39478233 DOI: 10.1038/s41551-024-01271-x
Abstract

Protein-protein interactions (PPIs) regulate signalling pathways and cell phenotypes, and the visualization of spatially resolved dynamics of PPIs would thus shed light on the activation and crosstalk of signalling networks. Here we report a method that leverages a sequential proximity ligation assay for the multiplexed profiling of PPIs with up to 47 proteins involved in multisignalling crosstalk pathways. We applied the method, followed by conventional immunofluorescence, to cell cultures and tissues of non-small-cell lung cancers with a mutated epidermal growth-factor receptor to determine the co-localization of PPIs in subcellular volumes and to reconstruct changes in the subcellular distributions of PPIs in response to perturbations by the tyrosine kinase inhibitor osimertinib. We also show that a graph convolutional network encoding spatially resolved PPIs can accurately predict the cell-treatment status of single cells. Multiplexed proximity ligation assays aided by graph-based deep learning can provide insights into the subcellular organization of PPIs towards the design of drugs for targeting the protein interactome.

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