Genome Biology (May 2025)

ONTraC characterizes spatially continuous variations of tissue microenvironment through niche trajectory analysis

  • Wen Wang,
  • Shiwei Zheng,
  • Sujung Crystal Shin,
  • Joselyn Cristina Chávez-Fuentes,
  • Guo-Cheng Yuan

DOI
https://doi.org/10.1186/s13059-025-03588-5
Journal volume & issue
Vol. 26, no. 1
pp. 1 – 20

Abstract

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Abstract Recent technological advances enable mapping of tissue spatial organization at single-cell resolution, but methods for analyzing spatially continuous microenvironments are still lacking. We introduce ONTraC, a graph neural network-based framework for constructing spatial trajectories at niche-level. Through benchmarking analyses using multiple simulated and real datasets, we show that ONTraC outperforms existing methods. ONTraC captures both normal anatomical structures and disease-associated tissue microenvironment changes. In addition, it identifies tissue microenvironment-dependent shifts in gene expression, regulatory network, and cell–cell interaction patterns. Taken together, ONTraC provides a useful framework for characterizing the structural and functional organization of tissue microenvironments.