Bering: joint cell segmentation and annotation for spatial transcriptomics with transferred graph embeddings.

Journal: Nature communications
Published Date:

Abstract

Single-cell spatial transcriptomics can provide subcellular resolution for a deep understanding of molecular mechanisms. However, accurate segmentation and annotation remain a major challenge that limits downstream analysis. Current machine learning methods heavily rely on nuclei or cell body staining, resulting in the significant loss of both transcriptome depth and the limited ability to learn spatial colocalization patterns. Here, we propose Bering, a graph deep learning model that leverages transcript colocalization relationships for joint noise-aware cell segmentation and molecular annotation in 2D and 3D spatial transcriptomics data. To evaluate performance, we benchmark Bering with state-of-the-art methods and observe better cell segmentation accuracies and more detected transcripts across technologies and tissues. To streamline segmentation processes, we construct expansive pre-trained models, which yield high segmentation accuracy in new data through transfer learning and self-distillation. These improved capabilities enable Bering to enhance cell annotations for the rapidly expanding field of spatial omics.

Authors

  • Kang Jin
    Department of Chemistry and Chemical Biology, Harvard University, Boston, MA, USA.
  • Zuobai Zhang
    Mila-Québec AI Institute, Montréal, QC, Canada.
  • Ke Zhang
    Center for Radiation Oncology, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou 310001, China.
  • Francesca Viggiani
    Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Claire Callahan
    Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Jian Tang
    Department of Decision Sciences HEC, Université de Montréal, Montreal, Québec, Canada.
  • Bruce J Aronow
    Department of Computer Science, University of Cincinnati, OH 45221, USA; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati, OH 45267, USA; Department of Biomedical Informatics, College of Medicine, University of Cincinnati, OH 45267, USA. Electronic address: bruce.aronow@cchmc.org.
  • Jian Shu
    Key Laboratory of Analysis and Detection for Food Safety (MOE and Fujian Province), Collaborative Innovation Center of Detection Technology for Haixi Food Safety and Products (Fujian Province), State Key Laboratory of Photocatalysis on Energy and Environment, Department of Chemistry, Fuzhou University , Fujian Province, China , 350002.