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            Spatial transcriptomics (ST) has emerged as a powerful technology for bridging histology imaging with gene expression profiling. However, its application has been limited by low throughput and the need for specialized experimental facilities. Prior works sought to predict ST from whole-slide histology images to accelerate this process, but they suffer from two major limitations. First, they do not explicitly model cell-cell interaction as they factorize the joint distribution of whole-slide ST data and predict the gene expression of each spot independently. Second, their encoders struggle with memory constraints due to the large number of spots (often exceeding 10,000) in typical ST datasets. Herein, we propose STFlow, a flow matching generative model that considers cell-cell interaction by modeling the joint distribution of gene expression of an entire slide. It also employs an efficient slide-level encoder with local spatial attention, enabling whole-slide processing without excessive memory overhead. On the recently curated HEST-1k and STImage-1K4M benchmarks, STFlow substantially outperforms state-of-the-art baselines and achieves over 18% relative improvements over the pathology foundation models.more » « lessFree, publicly-accessible full text available June 18, 2026
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            Huang, T; Song, Z; Ying, R; Jin, W (, Neural Information Processing Systems)Nucleic acid-based drugs like aptamers have recently demonstrated great therapeutic potential. However, experimental platforms for aptamer screening are costly, and the scarcity of labeled data presents a challenge for supervised methods to learn protein-aptamer binding. To this end, we develop an unsupervised learning approach based on the predicted pairwise contact map between a protein and a nucleic acid and demonstrate its effectiveness in protein-aptamer binding prediction. Our model is based on FAFormer, a novel equivariant transformer architecture that seamlessly integrates frame averaging (FA) within each transformer block. This integration allows our model to infuse geometric information into node features while preserving the spatial semantics of coordinates, leading to greater expressive power than standard FA models. Our results show that FAFormer outperforms existing equivariant models in contact map prediction across three protein complex datasets, with over 10% relative improvement. Moreover, we curate five real-world protein-aptamer interaction datasets and show that the contact map predicted by FAFormer serves as a strong binding indicator for aptamer screening.more » « lessFree, publicly-accessible full text available December 18, 2025
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