Unsupervised and supervised discovery of tissue cellular neighborhoods from cell phenotypes.

Journal: Nature methods
Published Date:

Abstract

It is poorly understood how different cells in a tissue organize themselves to support tissue functions. We describe the CytoCommunity algorithm for the identification of tissue cellular neighborhoods (TCNs) based on cell phenotypes and their spatial distributions. CytoCommunity learns a mapping directly from the cell phenotype space to the TCN space using a graph neural network model without intermediate clustering of cell embeddings. By leveraging graph pooling, CytoCommunity enables de novo identification of condition-specific and predictive TCNs under the supervision of sample labels. Using several types of spatial omics data, we demonstrate that CytoCommunity can identify TCNs of variable sizes with substantial improvement over existing methods. By analyzing risk-stratified colorectal and breast cancer data, CytoCommunity revealed new granulocyte-enriched and cancer-associated fibroblast-enriched TCNs specific to high-risk tumors and altered interactions between neoplastic and immune or stromal cells within and between TCNs. CytoCommunity can perform unsupervised and supervised analyses of spatial omics maps and enable the discovery of condition-specific cell-cell communication patterns across spatial scales.

Authors

  • Yuxuan Hu
    Leon H. Charney Division of Cardiology, NYU Langone Health, New York, NY, USA.
  • Jiazhen Rong
    Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Yafei Xu
    Department of Cell Biology and Genetics, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • Runzhi Xie
    School of Computer Science and Technology, Xidian University, Xi'an, China.
  • Jacqueline Peng
    School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Lin Gao
  • Kai Tan
    Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA. tank1@chop.edu.