# SCR2-ST: Combine Single Cell with Spatial Transcriptomics for Efficient Active Sampling via Reinforcement Learning Source: [SCR2-ST: Combine Single Cell with Spatial Transcriptomics for Efficient Active Sampling via Reinforcement Learning]() Collection index: [llms.txt]() Data updated: 2026-02-04T05:00:04.387Z Authors: Junchao Zhu, Ruining Deng, Junlin Guo, Tianyuan Yao, Chongyu Qu, Juming Xiong, Siqi Lu, Zhengyi Lu, Yanfan Zhu, Marilyn Lionts, Yuechen Yang, Yalin Zheng, Yu Wang, Shilin Zhao, Haichun Yang, Yuankai Huo Published: 2025-12-15T18:30:40.000Z ## Abstract 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 ## Recorded benchmark results A research result applies to its stated dataset, split, metric and evaluation configuration. Compare like-for-like settings, preserve the metric's unit and direction, and distinguish paper-reported results from independent reproduction. The best result recorded here is not a claim of exhaustive, current global coverage. - [Gene Expression Prediction on Breast Cancer](): gene expression prediction; Breast cancer; MSE: 0.5848. - [Gene expression prediction on Kidney](): gene expression prediction; Kidney; MSE: 0.7038. - [Gene Expression Prediction on HER2](): gene expression prediction; HER2; MSE: 0.9139. ## Original sources and implementation [Original paper]() [PDF]()