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SOFisher: reinforcement learning-guided experiment designs for spatial omics
Zhuo Li1, Weiran Wu1, Chuangyi Han2,3
1School of Automation, National Key Lab of Autonomous Intelligent Unmanned Systems, Beijing Institute of Technology, Beijing, China.
Nature Communications
|May 25, 2026
Summary
SOFisher, a reinforcement learning framework, optimizes spatial omics experimental design by intelligently selecting fields of view (FOVs). This AI-driven approach enhances efficiency and captures crucial biological insights from limited samples.
Area of Science:
- Spatial omics
- Computational biology
- Biotechnology
Background:
- Spatial omics technologies precisely map molecules like proteins and RNAs within tissues.
- Current field of view (FOV) sampling in spatial omics is often inefficient, requiring dense acquisition and stitching.
- Optimizing FOV selection is critical for maximizing data yield and minimizing resource expenditure.
Purpose of the Study:
- To develop an intelligent framework, SOFisher, for optimizing FOV sampling strategies in spatial omics experiments.
- To enhance the efficiency of capturing regions of interest using reinforcement learning.
- To enable deeper biological insights from reduced experimental footprints.
Main Methods:
- SOFisher, a reinforcement learning-based framework, guides sequential FOV selection.
- The framework learns from previously sampled FOVs to predict optimal next positions.
- Performance was evaluated using simulations on real spatial datasets and cross-domain generalization tests.
Main Results:
- SOFisher consistently outperformed conventional sampling strategies across various metrics.
- The framework demonstrated robustness and generalizability across different FOV sizes and datasets.
- Application on Alzheimer's Disease and colorectal cancer datasets revealed key biological insights, including cell states and gene programs, from limited FOVs.
Conclusions:
- SOFisher significantly improves the efficiency and effectiveness of spatial omics experimental design.
- The AI-driven approach can yield comprehensive biological insights comparable to traditional methods using fewer resources.
- SOFisher has the potential to revolutionize spatial biology experiment design, making complex analyses more accessible.

