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Updated: May 29, 2025

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Learning Phenotype Associated Signature in Spatial Transcriptomics with PASSAGE.

Chen-Kai Guo1,2, Chen-Rui Xia3,4, Guangdun Peng1,2

  • 1Center 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.

Small Methods
|February 5, 2025
PubMed
Summary
This summary is machine-generated.

Spatially resolved transcriptomics (SRT) analysis can now identify phenotype-associated spatial signatures using PASSAGE, a novel deep learning framework. This tool effectively characterizes cellular organization in complex tissues, improving disease and physiological state understanding.

Keywords:
deep learninggraph neural networkspatial signature identificationspatial transcriptomics

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Area of Science:

  • Genomics
  • Computational Biology
  • Bioinformatics

Background:

  • Spatially resolved transcriptomics (SRT) offers high-resolution insights into cellular organization in tissues.
  • Current computational tools for SRT primarily use unsupervised methods, neglecting crucial sample characteristics like disease states.
  • There is a need for advanced computational frameworks that integrate sample phenotypes into spatial transcriptomic analysis.

Purpose of the Study:

  • To introduce PASSAGE (Phenotype Associated Spatial Signature Analysis with Graph-based Embedding), a deep learning framework for phenotype-associated spatial signature analysis.
  • To enable the characterization of complex cellular patterns across multiple spatial slices, incorporating physiological and pathological states.
  • To provide a robust computational tool for advancing the understanding of tissue organization.

Main Methods:

  • Development of a deep learning framework named PASSAGE.
  • Utilizing graph-based embedding for spatial signature analysis.
  • Integrating phenotype information into the analysis of spatial transcriptomic data.

Main Results:

  • PASSAGE demonstrates outstanding performance in systematic benchmarks.
  • The framework effectively characterizes phenotype-associated spatial signatures across heterogeneous tissue slices.
  • PASSAGE successfully identified sophisticated signatures in real-world case studies.

Conclusions:

  • PASSAGE is a powerful deep learning tool for phenotype-associated spatial signature analysis in complex tissues.
  • The framework enhances the interpretation of spatial transcriptomic data by integrating sample characteristics.
  • PASSAGE advances the field of spatial transcriptomics for understanding tissue biology in health and disease.