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AIDO.Tissue: Spatial Cell-Guided Pretraining for Scalable Spatial Transcriptomics Foundation Model

Gong, J.; Wang, Y.; Ho, N.; Cheng, X.; Song, L.; Xing, E.

2025-07-07 bioinformatics
10.1101/2025.07.04.663102 bioRxiv
Show abstract

Single-cell spatial transcriptomics enables high-resolution insights into tissue organization and cell-cell interactions, yet poses significant computational and modeling challenges due to its scale and complexity. Here we introduce AIDO.Tissue, a spatially-informed pretraining framework. The design employs multiple cells as input and an asymmetric encoder-decoder architecture, making it effectively encodes cross-cell dependencies while scaling to large data. Systematic evaluation shows that our method scales with neighboring size and achieves state-of-the-art performance across diverse downstream tasks, including spatial cell type classification, cell niche type prediction and cell density estimation. These results highlight the importance of spatial context in building general-purpose foundation models for tissue-level understanding.

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