STAMarker: determining spatial domain-specific variable genes with saliency maps in deep learning.

Journal: Nucleic acids research
PMID:

Abstract

Spatial transcriptomics characterizes gene expression profiles while retaining the information of the spatial context, providing an unprecedented opportunity to understand cellular systems. One of the essential tasks in such data analysis is to determine spatially variable genes (SVGs), which demonstrate spatial expression patterns. Existing methods only consider genes individually and fail to model the inter-dependence of genes. To this end, we present an analytic tool STAMarker for robustly determining spatial domain-specific SVGs with saliency maps in deep learning. STAMarker is a three-stage ensemble framework consisting of graph-attention autoencoders, multilayer perceptron (MLP) classifiers, and saliency map computation by the backpropagated gradient. We illustrate the effectiveness of STAMarker and compare it with serveral commonly used competing methods on various spatial transcriptomic data generated by different platforms. STAMarker considers all genes at once and is more robust when the dataset is very sparse. STAMarker could identify spatial domain-specific SVGs for characterizing spatial domains and enable in-depth analysis of the region of interest in the tissue section.

Authors

  • Chihao Zhang
    NCMIS, CEMS, RCSDS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China.
  • Kangning Dong
    NCMIS, CEMS, RCSDS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China.
  • Kazuyuki Aihara
    Collaborative Research Center for Innovative Mathematical Modelling, Institute of Industrial Science, University of Tokyo, Japan.
  • Luonan Chen
    Key Laboratory of Systems Health Science of Zhejiang Province, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, 310024, China.
  • Shihua Zhang
    CEMS, NCMIS, HCMS, MDIS, RCSDS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, 100190, China.