SCR2-ST: Combine Single Cell with Spatial Transcriptomics for Efficient Active Sampling via Reinforcement Learning

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Auteurs principaux: Zhu, Junchao, Deng, Ruining, Guo, Junlin, Yao, Tianyuan, Qu, Chongyu, Xiong, Juming, Lu, Siqi, Lu, Zhengyi, Zhu, Yanfan, Lionts, Marilyn, Yang, Yuechen, Zheng, Yalin, Wang, Yu, Zhao, Shilin, Yang, Haichun, Huo, Yuankai
Format: Preprint
Publié: 2025
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author Zhu, Junchao
Deng, Ruining
Guo, Junlin
Yao, Tianyuan
Qu, Chongyu
Xiong, Juming
Lu, Siqi
Lu, Zhengyi
Zhu, Yanfan
Lionts, Marilyn
Yang, Yuechen
Zheng, Yalin
Wang, Yu
Zhao, Shilin
Yang, Haichun
Huo, Yuankai
author_facet Zhu, Junchao
Deng, Ruining
Guo, Junlin
Yao, Tianyuan
Qu, Chongyu
Xiong, Juming
Lu, Siqi
Lu, Zhengyi
Zhu, Yanfan
Lionts, Marilyn
Yang, Yuechen
Zheng, Yalin
Wang, Yu
Zhao, Shilin
Yang, Haichun
Huo, Yuankai
contents Spatial transcriptomics (ST) is an emerging technology that enables researchers to investigate the molecular relationships underlying tissue morphology. However, acquiring ST data remains prohibitively expensive, and traditional fixed-grid sampling strategies lead to redundant measurements of morphologically similar or biologically uninformative regions, thus resulting in scarce data that constrain current methods. The well-established single-cell sequencing field, however, could provide rich biological data as an effective auxiliary source to mitigate this limitation. To bridge these gaps, we introduce SCR2-ST, a unified framework that leverages single-cell prior knowledge to guide efficient data acquisition and accurate expression prediction. SCR2-ST integrates a single-cell guided reinforcement learning-based (SCRL) active sampling and a hybrid regression-retrieval prediction network SCR2Net. SCRL combines single-cell foundation model embeddings with spatial density information to construct biologically grounded reward signals, enabling selective acquisition of informative tissue regions under constrained sequencing budgets. SCR2Net then leverages the actively sampled data through a hybrid architecture combining regression-based modeling with retrieval-augmented inference, where a majority cell-type filtering mechanism suppresses noisy matches and retrieved expression profiles serve as soft labels for auxiliary supervision. We evaluated SCR2-ST on three public ST datasets, demonstrating SOTA performance in both sampling efficiency and prediction accuracy, particularly under low-budget scenarios. Code is publicly available at: https://github.com/hrlblab/SCR2ST
format Preprint
id arxiv_https___arxiv_org_abs_2512_13635
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle SCR2-ST: Combine Single Cell with Spatial Transcriptomics for Efficient Active Sampling via Reinforcement Learning
Zhu, Junchao
Deng, Ruining
Guo, Junlin
Yao, Tianyuan
Qu, Chongyu
Xiong, Juming
Lu, Siqi
Lu, Zhengyi
Zhu, Yanfan
Lionts, Marilyn
Yang, Yuechen
Zheng, Yalin
Wang, Yu
Zhao, Shilin
Yang, Haichun
Huo, Yuankai
Computer Vision and Pattern Recognition
Spatial transcriptomics (ST) is an emerging technology that enables researchers to investigate the molecular relationships underlying tissue morphology. However, acquiring ST data remains prohibitively expensive, and traditional fixed-grid sampling strategies lead to redundant measurements of morphologically similar or biologically uninformative regions, thus resulting in scarce data that constrain current methods. The well-established single-cell sequencing field, however, could provide rich biological data as an effective auxiliary source to mitigate this limitation. To bridge these gaps, we introduce SCR2-ST, a unified framework that leverages single-cell prior knowledge to guide efficient data acquisition and accurate expression prediction. SCR2-ST integrates a single-cell guided reinforcement learning-based (SCRL) active sampling and a hybrid regression-retrieval prediction network SCR2Net. SCRL combines single-cell foundation model embeddings with spatial density information to construct biologically grounded reward signals, enabling selective acquisition of informative tissue regions under constrained sequencing budgets. SCR2Net then leverages the actively sampled data through a hybrid architecture combining regression-based modeling with retrieval-augmented inference, where a majority cell-type filtering mechanism suppresses noisy matches and retrieved expression profiles serve as soft labels for auxiliary supervision. We evaluated SCR2-ST on three public ST datasets, demonstrating SOTA performance in both sampling efficiency and prediction accuracy, particularly under low-budget scenarios. Code is publicly available at: https://github.com/hrlblab/SCR2ST
title SCR2-ST: Combine Single Cell with Spatial Transcriptomics for Efficient Active Sampling via Reinforcement Learning
topic Computer Vision and Pattern Recognition
url https://arxiv.org/abs/2512.13635