Graph deep learning for the characterization of tumour microenvironments from spatial protein profiles in tissue specimens.

Journal: Nature biomedical engineering
Published Date:

Abstract

Multiplexed immunofluorescence imaging allows the multidimensional molecular profiling of cellular environments at subcellular resolution. However, identifying and characterizing disease-relevant microenvironments from these rich datasets is challenging. Here we show that a graph neural network that leverages spatial protein profiles in tissue specimens to model tumour microenvironments as local subgraphs captures distinctive cellular interactions associated with differential clinical outcomes. We applied this spatial cellular-graph strategy to specimens of human head-and-neck and colorectal cancers assayed with 40-plex immunofluorescence imaging to identify spatial motifs associated with cancer recurrence and with patient survival after treatment. The graph deep learning model was substantially more accurate in predicting patient outcomes than deep learning approaches that model spatial data on the basis of the local composition of cell types, and it generated insights into the effect of the spatial compartmentalization of tumour cells and granulocytes on patient prognosis. Local graphs may also aid in the analysis of disease-relevant motifs in histology samples characterized via spatial transcriptomics and other -omics techniques.

Authors

  • Zhenqin Wu
    Department of Chemistry , Stanford University , Stanford , CA 94305 , USA . Email: pande@stanford.edu.
  • Alexandro E Trevino
    Enable Medicine, Menlo Park, CA, USA. alex@enablemedicine.com.
  • Eric Wu
    Department of Electrical Engineering, Stanford University, Stanford, CA, USA.
  • Kyle Swanson
  • Honesty J Kim
    Enable Medicine, Menlo Park, CA, USA.
  • H Blaize D'Angio
    Enable Medicine, Menlo Park, CA, USA.
  • Ryan Preska
    Enable Medicine, Menlo Park, CA, USA.
  • Gregory W Charville
    Department of Pathology, Stanford University, Stanford, CA, USA.
  • Piero D Dalerba
    Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
  • Ann Marie Egloff
    Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
  • Ravindra Uppaluri
    Department of Surgery/Otolaryngology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA, USA.
  • Umamaheswar Duvvuri
    Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh Medical Center Pittsburgh, Pennsylvania4Department of Otolaryngology, Veterans Affairs Pittsburgh Health System, Pittsburgh, Pennsylvania.
  • Aaron T Mayer
    Enable Medicine, Menlo Park, CA, USA. aaron@enablemedicine.com.
  • James Zou
    Department of Biomedical Data Science, Stanford University, Stanford, California.