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Modeling Microenvironment Trajectories on Spatial Transcriptomics with NicheFlow

Overview of NicheFlow. At time t1, we generate a target microenvironment M1 by transforming Gaussian noise Mz using a Variational Flow Matching model with a posterior conditioned on a source microenvironment M0 at t0. Source-target pairs are identified via entropic OT over pooled microenvironment coordinates and gene expression profiles.

Abstract

Understanding the evolution of cellular microenvironments is essential for deciphering tissue development and disease progression. While spatial transcriptomics now enables high-resolution mapping of tissue organization across space and time, current techniques that analyze cellular evolution operate at the single-cell level, overlooking critical spatial relationships. We introduce NicheFlow, a flow-based generative model that infers the temporal trajectory of cellular microenvironments across sequential spatial slides. By representing local cell neighborhoods as point clouds, NicheFlow jointly models the evolution of cell states and coordinates using optimal transport and Variational Flow Matching. Our approach successfully recovers both global spatial architecture and local microenvironment composition across diverse spatio-temporal datasets, from embryonic to brain development.

Links

[Paper | GitHub]

Citation

Modeling Microenvironment Trajectories on Spatial Transcriptomics with NicheFlow
Kristiyan Sakalyan*, Alessandro Palma*, Filippo Guerranti*, Fabian J Theis, Stephan Günnemann
NeurIPS, 2025

If you use this work in your research, please cite this paper:

@inproceedings{sakalayan2025nicheflow,  

    title={Modeling Microenvironment Trajectories on Spatial Transcriptomics with NicheFlow},

    author={Sakalayan, Kristiyan and Palma, Alessandro and Guerranti, Filippo and Theis, Fabian and G{\"u}nnemann, Stephan},  

    booktitle={Neural Information Processing Systems (NeurIPS)},  

    year={2025},  

    url={https://openreview.net/forum?id=5ofJyjgrth} 

}

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Informatik 26 - Data Analytics and Machine Learning


Prof. Dr. Stephan Günnemann

Technische Universität München
TUM School of Computation, Information and Technology
Department of Computer Science
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85748 Garching 

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