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M2OST: Many-to-one Regression for Predicting Spatial Transcriptomics from Digital Pathology Images

AAAI 2025 · Image generation › Autoregressive and latent generation · approach: Retrieval and matching with generative features · 8 citations (OpenAlex)

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Proposes M2OST, a many-to-one Transformer that jointly predicts a spot's spatial gene expression from three pyramid levels of the same WSI patch, with decoupled intra-level, cross-level token and channel mixing.

Problem

Predicting spatial transcriptomics (ST) gene expression from histopathology whole slide images; existing patch-level regression methods ignore multi-scale pyramid information and inter-spot visual context, and slide-level methods are large and costly.

Approach

Treat ST prediction as many-to-one regression: multiple magnification levels of the same spot are fed through weight-decoupled streams with deformable patch embedding, cross-level attention and cross-level channel mixing, yielding a compact Transformer with fewer parameters and FLOPs.

Key results

Measured effects reported in the paper

What was changedWhereMeasuredEffect
Add DPE instead of ordinary patch embedding (ablation)M2OST · HBC, HER2+, and cSCCPCC (%): 47.13 -> 48.07; 43.10 -> 44.17; 49.35 -> 50.50Helped
Use separate ITMMs rather than unified self-attention (ablation)M2OST · HBC, HER2+, and cSCCPCC (%): 47.03 -> 48.07; 42.99 -> 44.17; 49.48 -> 50.50Helped
Add CTMM instead of simple concatenation for cross-level fusion (ablation)M2OST · HBC, HER2+, and cSCCPCC (%): 46.34 -> 48.07; 42.57 -> 44.17; 48.81 -> 50.50Helped
Use CCMM instead of ordinary fully connected layers for channel mixing (ablation)M2OST · HBC, HER2+, and cSCCPCC (%): 46.12 -> 48.07; 42.55 -> 44.17; 48.66 -> 50.50Helped
Add level 1 and level 2 image patches to level 0 inputs (ablation)M2OST · HBC, HER2+, and cSCCPCC (%): 46.92 -> 48.07; 43.12 -> 44.17; 49.31 -> 50.50Helped
Mask one random input level in more samples (ablation)M2OST on the fused dataset · HBC, HER2+, and cSCCPCC (%): 39.46 -> 31.71; 39.97 -> 32.32; 37.33 -> 34.19Hurt
Apply many-to-one modeling with ResNet-50 patch embeddings (ablation)ResNet-50 · HBC, HER2+, and cSCCPCC (%): +1.71; +1.43; +1.46Helped
Apply many-to-one modeling with ST-Net patch embeddings (ablation)ST-Net · HBC, HER2+, and cSCCPCC (%): +1.12; +1.72; +1.39Helped
Apply many-to-one modeling with ViT patch embeddings (ablation)ViT · HBC, HER2+, and cSCCPCC (%): +1.95; +0.63; +1.81Helped

Surprising findings

Limitations

Experimental setup

Datasets: HBC HER2+ cSCC

Benchmarks: HBC HER2+ cSCC

Metrics: PCC RMSE parameter count FLOPs

Baselines: ResNet50 ViT-B/16 Swin-T ConvNeXt-T CrossViT DeepSpaCE ST-Net HisToGene Hist2ST BLEEP HIPT/iStar

Builds on: ViT CrossViT Random Mask Self-Attention squeeze-and-excitation

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