# SpaVGN: A hybrid deep learning framework for high-resolution spatial transcriptomics data reconstruction and spatial domain identification

**Authors:** Haiyan Wang, Yanping Zhang, Yangyang Zhang, Xuening Zhao, Zijia Bai, Xuejing Ma, Chunguang Zhao

PMC · DOI: 10.1371/journal.pone.0329122 · PLOS One · 2025-08-14

## TL;DR

SpaVGN is a deep learning framework that improves the resolution and accuracy of spatial transcriptomics data, enabling better analysis of tissue structure and function.

## Contribution

SpaVGN introduces a hybrid deep learning model combining CNNs, vision transformers, and graph neural networks for spatial transcriptomics.

## Key findings

- SpaVGN outperformed existing methods with Pearson correlation coefficients of 0.609 (melanoma) and 0.682 (mouse brain).
- It achieved fine-grained resolution of hippocampal subfields with a Silhouette Score of 0.43 and a Davies-Bouldin Index of 0.86.
- Validation showed SpaVGN improves data completeness and spatial continuity in spatial transcriptomics.

## Abstract

Spatial transcriptomics has revolutionized the analysis of gene expression while preserving tissue spatial information, which provides novel insights into the cellular composition and function of complex biological tissues. However, current technologies are constrained by limited resolution and data sparsity, compromising the accuracy of downstream analyses. To address these challenges, we developed SpaVGN, a deep learning framework integrating convolutional neural networks, vision transformer, and graph neural networks for high-fidelity gene expression imputation and spatial domain identification. By combining local feature extraction, global attention mechanisms, and spatial graph-based modeling, SpaVGN effectively reconstructs missing transcriptomic data while preserving spatial tissue architecture. Evaluated on melanoma and sagittal posterior mouse brain datasets, SpaVGN outperformed existing methods in gene expression prediction, achieving Pearson correlation coefficients of 0.609 (melanoma) and 0.682 (mouse brain). It clearly delineated tumor regions and lymphoid niches in melanoma tissue, achieving fine-grained resolution of hippocampal subfields, including Cornu Ammonis and Dentate Gyrus, with a Silhouette Score of 0.43 and a Davies-Bouldin Index of 0.86. Validation through UMAP dimensionality reduction and PAGA network analysis demonstrated that SpaVGN significantly mitigates the negative impact of data sparsity in spatial transcriptomics, improving data completeness and spatial continuity. This study presents an innovative solution that enhances the resolution of spatial transcriptomics data, offering cross-tissue applicability and providing a valuable tool for research in biological development, disease, and tumor heterogeneity.

## Linked entities

- **Diseases:** melanoma (MONDO:0005105)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Vit (vitrin) [NCBI Gene 74199] {aka 1700052E02Rik, 1700110E08Rik, 2810429K11Rik, AKH, akhirin}, Dll3 (delta like canonical Notch ligand 3) [NCBI Gene 13389] {aka pu, pudgy}, Tpt1 (tumor protein, translationally-controlled 1) [NCBI Gene 22070] {aka TCTP, Trt, p21, p23}, Erbb2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 13866] {aka Erbb-2, HER-2, HER2, Neu, c-erbB2, c-neu}, Rps25 (ribosomal protein S25) [NCBI Gene 75617] {aka 2810009D21Rik}, Cd37 (CD37 antigen) [NCBI Gene 12493] {aka Tspan26}, Ms4a1 (membrane-spanning 4-domains, subfamily A, member 1) [NCBI Gene 12482] {aka Cd20, Ly-44, Ms4a2}
- **Diseases:** UMAP (MESH:C567162), tumor (MESH:D009369), melanoma (MESH:D008545)
- **Chemicals:** H&amp;E (MESH:D006371)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

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## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC12352682/full.md

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Source: https://tomesphere.com/paper/PMC12352682