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arXiv:2611.02681 · v1

HistoTx: Early fusion of H&E images and spatial transcriptomics at varying spatial transcriptomics resolution with self-supervised learning

首次提交 2026-11-02 15:36
版本更新 2026-11-02 15:36
雷达观测 2026-11-04 23:42
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摘要

Spatial transcriptomics maps gene expression across tissue sections and, when integrated with whole slide images, jointly captures both morphological architecture and molecular activity to provide a rich, multimodal view of tissue biology. ML approaches combining spatial transcriptomics and WSIs typically learn a mapping from morphological features to molecular profiles via contrastive alignment or supervised fine-tuning of pathology foundation models. In both cases, transcriptomics serves as a training signal rather than a true input modality, leaving inference fundamentally image-driven. We propose an early-fusion vision transformer architecture in which transcript tokens are constructed at arbitrary spatial resolution, merged with image patch tokens, and jointly processed through a shared transformer stack for deep cross-modal interaction. Starting from a pretrained vision-only pathology foundation model, we train HistoTx by continuing self-supervised pretraining on paired image and spatial transcriptomics data and demonstrate that: 1) at inference with image only, performance remains on par with the baseline on most tasks while improving on tasks that inherently benefit from molecular knowledge, such as gene expression prediction; 2) when both modalities are available at inference, jointly providing image and transcript inputs outperforms either modality alone.

作者备注:Presented at 3rd Workshop on Multi-modal Foundation Models and Large Language Models for Life Sciences (ICML 2026)

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v1 · 2026-11-02 15:36 · 最新观测版本

HistoTx: Early fusion of H&E images and spatial transcriptomics at varying spatial transcriptomics resolution with self-supervised learning

Spatial transcriptomics maps gene expression across tissue sections and, when integrated with whole slide images, jointly captures both morphological architecture and molecular activity to provide a rich, multimodal view of tissue biology. ML approaches combining spatial transcriptomics and WSIs typically learn a mapping from morphological features to molecular profiles via contrastive alignment or supervised fine-tuning of pathology foundation models. In both cases, transcriptomics serves as a training signal rather than a true input modality, leaving inference fundamentally image-driven. We propose an early-fusion vision transformer architecture in which transcript tokens are constructed at arbitrary spatial resolution, merged with image patch tokens, and jointly processed through a shared transformer stack for deep cross-modal interaction. Starting from a pretrained vision-only pathology foundation model, we train HistoTx by continuing self-supervised pretraining on paired image and spatial transcriptomics data and demonstrate that: 1) at inference with image only, performance remains on par with the baseline on most tasks while improving on tasks that inherently benefit from molecular knowledge, such as gene expression prediction; 2) when both modalities are available at inference, jointly providing image and transcript inputs outperforms either modality alone.

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