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ASIGN: An Anatomy-aware Spatial Imputation Graphic Network for 3D Spatial Transcriptomics
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Introduces 3D spatial transcriptomics imputation from 3D WSI sections plus one 2D ST slide, using a graph network (ASIGN) with cross-layer label propagation.
Problem
Full 3D spatial transcriptomics is prohibitively expensive, and existing WSI-to-ST predictors work only on single 2D sections and generalize poorly across samples.
Approach
Builds a 3D spot graph by registering WSI layers (XFeat + ANTs) and linking spots across layers via overlap and similarity; a multi-level spatial attention graph network (MSAGNet) fuses multi-resolution patches and GAT/Transformer layers, and a cross-layer imputation block propagates labels from one known ST layer to unknown layers.
Key results
- ASIGN 3D reaches PCC 0.693 on HER2 versus 0.649 for the best 3D baseline (similarity) and 0.441 for His2ST's 2D setting, per the reported table.
- On DLPFC, ASIGN 3D achieves PCC 0.739 vs 0.663 for the best 3D baseline; on ST-Data, ASIGN 2D is competitive with 2D baselines.
- Cross-layer imputation raises HER2 PCC from 0.635 to 0.693 with 20% known labels, with performance plateauing at 20-30%.
Measured effects reported in the paper
| What was changed | Where | Measured | Effect |
|---|---|---|---|
| use ASIGN 2D instead of the strongest 2D baseline, EGN | 2D WSI-wise ST prediction · HER2 | PCC: 0.442 -> 0.476 | Helped |
| use ASIGN 2D instead of the strongest 2D baseline, His2ST | 2D WSI-wise ST prediction · DLPFC | PCC: 0.764 -> 0.766 | Helped |
| use ASIGN 2D instead of the strongest 2D baseline, EGN | 2D WSI-wise ST prediction · ST-Data | PCC: 0.554 -> 0.552 | No clear effect |
| use ASIGN 3D instead of the strongest 3D baseline, Similarity | 3D sample-wise ST prediction · HER2 | PCC: 0.649 -> 0.693 | Helped |
| use ASIGN 3D instead of the strongest 3D baseline, Similarity | 3D sample-wise ST prediction · DLPFC | PCC: 0.762 -> 0.773 | Helped |
| use ASIGN 3D instead of the strongest 3D baseline, Similarity | 3D sample-wise ST prediction · ST-Data | PCC: 0.696 -> 0.739 | Helped |
| add cross-attention and GAT blocks (ablation) | ASIGN · HER2 | PCC: 0.659 -> 0.693 | Helped |
| add cross-attention (ablation) | ASIGN · HER2 | PCC: 0.686 -> 0.693 | Helped |
| add GAT blocks (ablation) | ASIGN · HER2 | PCC: 0.677 -> 0.693 | Helped |
| add CLI label propagation with 20% known labels instead of no CLI (ablation) | ASIGN · HER2 | PCC: 0.635 -> 0.693 | Helped |
| increase known-label proportion from 20% to 30% (ablation) | ASIGN CLI block · HER2 | PCC: 0.693 -> 0.708 | Helped |
| increase known-label proportion from 20% to 40% (ablation) | ASIGN CLI block · HER2 | PCC: 0.693 -> 0.703 | Helped |
Surprising findings
- Adding the 3D sample-level graph raised PCC on HER2 from 0.476 to 0.635, showing that spatial context across layers matters more than 2D modeling alone.
Limitations
- Evaluated on only three public datasets with small sample counts (3-23 samples).
- Requires one ST-profiled layer per sample as known labels; the 3D setting depends on accurate registration of WSI layers.
Experimental setup
Datasets: HER2 DLPFC ST-Data
Benchmarks: HER2 DLPFC ST-Data
Metrics: PCC MSE MAE
Baselines: ST-Net EGN HisToGene BLEEP His2ST PASTE-inspired overlap imputation PASTE-inspired similarity imputation
Builds on: TRIPLEX PASTE ST-Net BLEEP
Closest papers by meaning
- HEST-1k: A Dataset For Spatial Transcriptomics and Histology Image Analysis (NeurIPS 2024 · similarity 0.87)
- Diffusion Generative Modeling for Spatially Resolved Gene Expression Inference from Histology Images (ICLR 2025 · similarity 0.87)
- Scalable Generation of Spatial Transcriptomics from Histology Images via Whole-Slide Flow Matching (ICML 2025 · similarity 0.86)
- STINR: Deciphering Spatial Transcriptomics via Implicit Neural Representation (CVPR 2025 · similarity 0.86)
- M2OST: Many-to-one Regression for Predicting Spatial Transcriptomics from Digital Pathology Images (AAAI 2025 · similarity 0.86)
- MEATRD: Multimodal Anomalous Tissue Region Detection Enhanced with Spatial Transcriptomics (AAAI 2025 · similarity 0.86)
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