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PHD-MS: Multiscale Domain Identification for Spatial Transcriptomics via Persistent Homology.

Perry Beamer1, Zixuan Cang1,2

  • 1Department of Mathematics, North Carolina State University, Raleigh, NC, USA.

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|November 26, 2025
PubMed
Summary
This summary is machine-generated.

This study introduces Persistent Homology for Domains at Multiple Scales (PHD-MS), a new method using topological data analysis to identify spatial domains across various scales in tissues. PHD-MS enhances spatial transcriptomics analysis by revealing multiscale tissue structures.

Keywords:
Multiscale domainsSpatial transcriptomicsTopological data analysis

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Area of Science:

  • Genomics
  • Computational Biology
  • Biotechnology

Background:

  • Spatial transcriptomics (ST) reveals gene expression within tissue microenvironments.
  • Current ST clustering methods often focus on single scales, missing multiscale spatial domain interactions.
  • Understanding multiscale tissue organization is crucial for biological insights.

Purpose of the Study:

  • To develop a novel method for identifying spatial domains at multiple morphological scales.
  • To address limitations of single-scale clustering in spatial transcriptomics.
  • To provide a tool for exploring persistent tissue structures across scales.

Main Methods:

  • Application of Topological Data Analysis (TDA) to spatial transcriptomics data.
  • Development of Persistent Homology for Domains at Multiple Scales (PHD-MS).
  • Utilizing TDA to identify tissue structures that persist across various geometric scales.

Main Results:

  • PHD-MS successfully identified multiscale spatial domains in diverse tissue types and ST technologies.
  • The method highlights persistent tissue structures across different morphological scales.
  • PHD-MS demonstrated superior performance compared to traditional clustering methods against expert-annotated ground truth.

Conclusions:

  • PHD-MS effectively captures multiscale spatial organization in tissues.
  • The developed method offers a significant advancement for spatial transcriptomics data analysis.
  • PHD-MS is available as an open-source package with a user-friendly interface for broader accessibility.