用强化学习结合单细胞数据,高效采样空间转录组,节省成本。
SCR2-ST: Combine Single Cell with Spatial Transcriptomics for Efficient Active Sampling via Reinforcement Learning
- 基于单细胞嵌入与空间密度设计奖励信号,智能选择高信息量区域采样。
- 在低预算下采样效率提升30%,表达预测准确率优于现有方法。
- 适合需降低成本的空间转录组研究者,尤其关注数据稀缺场景。
空间转录组学(ST)能揭示组织形态与分子关系,但数据获取成本高昂,传统固定网格采样常重复测量无意义区域,导致数据稀少限制分析。单细胞测序可提供丰富生物先验数据,缓解此问题。为此,我们提出SCR2-ST框架,融合单细胞先验知识以实现高效数据采集与精准表达预测。该框架包含基于单细胞引导的强化学习主动采样(SCRL)和混合回归-检索预测网络SCR2Net。SCRL利用单细胞基础模型嵌入与空间密度构建生物学合理的奖励信号,在有限测序预算下选择高信息量组织区域。SCR2Net则通过混合架构,结合回归建模与检索增强推理,多数细胞类型过滤机制抑制噪声匹配,检索到的表达谱作为软标签辅助监督。我们在三个公开ST数据集上验证,无论采样效率还是预测精度均达当前最优,尤其在低预算下表现突出。代码已开源:https://github.com/hrlblab/SCR2ST
原文摘要 · Abstract (English)
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
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