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

arXiv: https://arxiv.org/abs/2512.13635 · HTML: https://mlsanity.com/paper/2512.13635/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 9 of its 33 references that are in the map.
- First posted on arXiv 15 Dec 2025.

## Builds on (most cited first, 9 of 9)

- [Densely Connected Convolutional Networks](https://mlsanity.com/paper/1608.06993/) (2016)
- [Diverse mini-batch Active Learning](https://mlsanity.com/paper/1901.05954/) (2019)
- [Spatially Resolved Gene Expression Prediction from H&E Histology Images via Bi-modal Contrastive Learning](https://mlsanity.com/paper/2306.01859/) (2023)
- [Accurate Spatial Gene Expression Prediction by integrating Multi-resolution features](https://mlsanity.com/paper/2403.07592/) (2024)
- [Exemplar Guided Deep Neural Network for Spatial Transcriptomics Analysis of Gene Expression Prediction](https://mlsanity.com/paper/2210.16721/) (2022)
- [Multimodal contrastive learning for spatial gene expression prediction using histology images](https://mlsanity.com/paper/2407.08216/) (2024)
- [Entropic Open-set Active Learning](https://mlsanity.com/paper/2312.14126/) (2023)
- [MagNet: Multi-Level Attention Graph Network for Predicting High-Resolution Spatial Transcriptomics](https://mlsanity.com/paper/2502.21011/) (2025)
- [Img2ST-Net: Efficient High-Resolution Spatial Omics Prediction from Whole Slide Histology Images via Fully Convolutional Image-to-Image Learning](https://mlsanity.com/paper/2508.14393/) (2025)

## Built on by (most cited first, 1 of 1)

- [DUET: Dual-Paradigm Adaptive Expert Triage with Single-cell Inductive Prior for Spatial Transcriptomics Prediction](https://mlsanity.com/paper/2605.14104/) (2026)

## Abstract (arXiv)

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