Learning Phenotype Associated Signature in Spatial Transcriptomics with PASSAGE.

Journal: Small methods
Published Date:

Abstract

Spatially resolved transcriptomics (SRT) is poised to advance the understanding of cellular organization within complex tissues under various physiological and pathological conditions at unprecedented resolution. Despite the development of numerous computational tools that facilitate the automatic identification of statistically significant intra-/inter-slice patterns (like spatial domains), these methods typically operate in an unsupervised manner, without leveraging sample characteristics like physiological/pathological states. Here PASSAGE (Phenotype Associated Spatial Signature Analysis with Graph-based Embedding), a rationally-designed deep learning framework is presented for characterizing phenotype-associated signatures across multiple heterogeneous spatial slices effectively. In addition to its outstanding performance in systematic benchmarks, PASSAGE's unique capability in calling sophisticated signatures has been demonstrated in multiple real-world cases. The full package of PASSAGE is available at https://github.com/gao-lab/PASSAGE.

Authors

  • Chen-Kai Guo
    Center for Cell Lineage and Development, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, University of Chinese Academy of Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
  • Chen-Rui Xia
    State Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Biomedical Pioneering Innovative Center (BIOPIC) and Beijing Advanced Innovation Center for Genomics (ICG), Center for Bioinformatics (CBI), Peking University, Beijing, 100871, China.
  • Guangdun Peng
    Center for Cell Lineage and Development, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, University of Chinese Academy of Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
  • Zhi-Jie Cao
    State Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Biomedical Pioneering Innovative Center (BIOPIC) and Beijing Advanced Innovation Center for Genomics (ICG), Center for Bioinformatics (CBI), Peking University, Beijing, 100871, China.
  • Ge Gao
    School of Computer Science and Artificial Intelligence, Aliyun School of Big Data, School of Software, Changzhou University, Changzhou 213000, China.