# Gene-DML: Dual-Pathway Multi-Level Discrimination for Gene Expression Prediction from Histopathology Images

arXiv: https://arxiv.org/abs/2507.14670 · HTML: https://mlsanity.com/paper/2507.14670/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 30 of its 50 references that are in the map.
- First posted on arXiv 19 Jul 2025.

## Builds on (most cited first, 30 of 30)

- [Learning Transferable Visual Models From Natural Language Supervision](https://mlsanity.com/paper/2103.00020/) (2021)
- [Densely Connected Convolutional Networks](https://mlsanity.com/paper/1608.06993/) (2016)
- [Gaussian Error Linear Units (GELUs)](https://mlsanity.com/paper/1606.08415/) (2016)
- [Scaling Vision Transformers to Gigapixel Images via Hierarchical Self-Supervised Learning](https://mlsanity.com/paper/2206.02647/) (2022)
- [Patches Are All You Need?](https://mlsanity.com/paper/2201.09792/) (2022)
- [HEST-1k: A Dataset for Spatial Transcriptomics and Histology Image Analysis](https://mlsanity.com/paper/2406.16192/) (2024)
- [Spatially Resolved Gene Expression Prediction from H&E Histology Images via Bi-modal Contrastive Learning](https://mlsanity.com/paper/2306.01859/) (2023)
- [CrossCLR: Cross-modal Contrastive Learning For Multi-modal Video Representations](https://mlsanity.com/paper/2109.14910/) (2021)
- [Twin Contrastive Learning for Online Clustering](https://mlsanity.com/paper/2210.11680/) (2022)
- [Accurate Spatial Gene Expression Prediction by integrating Multi-resolution features](https://mlsanity.com/paper/2403.07592/) (2024)
- [Unsupervised Feature Learning by Cross-Level Instance-Group Discrimination](https://mlsanity.com/paper/2008.03813/) (2020)
- [Exemplar Guided Deep Neural Network for Spatial Transcriptomics Analysis of Gene Expression Prediction](https://mlsanity.com/paper/2210.16721/) (2022)
- [Diffusion Generative Modeling for Spatially Resolved Gene Expression Inference from Histology Images](https://mlsanity.com/paper/2501.15598/) (2025)
- [ContIG: Self-supervised Multimodal Contrastive Learning for Medical Imaging with Genetics](https://mlsanity.com/paper/2111.13424/) (2021)
- [Multimodal contrastive learning for spatial gene expression prediction using histology images](https://mlsanity.com/paper/2407.08216/) (2024)
- [Beyond Gaussians: Fast and High-Fidelity 3D Splatting with Linear Kernels](https://mlsanity.com/paper/2411.12440/) (2024)
- [MERGE: Multi-faceted Hierarchical Graph-based GNN for Gene Expression Prediction from Whole Slide Histopathology Images](https://mlsanity.com/paper/2412.02601/) (2024)
- [M2OST: Many-to-one Regression for Predicting Spatial Transcriptomics from Digital Pathology Images](https://mlsanity.com/paper/2409.15092/) (2024)
- [ST-Align: A Multimodal Foundation Model for Image-Gene Alignment in Spatial Transcriptomics](https://mlsanity.com/paper/2411.16793/) (2024)
- [TED-VITON: Transformer-Empowered Diffusion Models for Virtual Try-On](https://mlsanity.com/paper/2411.17017/) (2024)
- [DSNet: A Dual-Stream Framework for Weakly-Supervised Gigapixel Pathology Image Analysis](https://mlsanity.com/paper/2109.05788/) (2021)
- [Cross-modal Diffusion Modelling for Super-resolved Spatial Transcriptomics](https://mlsanity.com/paper/2404.12973/) (2024)
- [Learning to Generalize over Subpartitions for Heterogeneity-aware Domain Adaptive Nuclei Segmentation](https://mlsanity.com/paper/2401.09496/) (2024)
- [Spatial Transcriptomics Analysis of Zero-shot Gene Expression Prediction](https://mlsanity.com/paper/2401.14772/) (2024)
- [A Dual-branch Self-supervised Representation Learning Framework for Tumour Segmentation in Whole Slide Images](https://mlsanity.com/paper/2303.11019/) (2023)
- [Multi-scale Efficient Graph-Transformer for Whole Slide Image Classification](https://mlsanity.com/paper/2305.15773/) (2023)
- [Revisiting Adaptive Cellular Recognition Under Domain Shifts: A Contextual Correspondence View](https://mlsanity.com/paper/2407.12870/) (2024)
- [RankByGene: Gene-Guided Histopathology Representation Learning Through Cross-Modal Ranking Consistency](https://mlsanity.com/paper/2411.15076/) (2024)
- [MIRROR: Multi-Modal Pathological Self-Supervised Representation Learning via Modality Alignment and Retention](https://mlsanity.com/paper/2503.00374/) (2025)
- [SpaRED benchmark: Enhancing Gene Expression Prediction from Histology Images with Spatial Transcriptomics Completion](https://mlsanity.com/paper/2407.13027/) (2024)

## Built on by (most cited first, 1 of 1)

- [RNA-FM: Flow-Matching Generative Model for Genome-wide RNA-Seq Prediction](https://mlsanity.com/paper/2605.11622/) (2026)

## Abstract (arXiv)

Accurately predicting gene expression from histopathology images offers a scalable and non-invasive approach to molecular profiling, with significant implications for precision medicine and computational pathology. However, existing methods often underutilize the cross-modal representation alignment between histopathology images and gene expression profiles across multiple representational levels, thereby limiting their prediction performance. To address this, we propose Gene-DML, a unified framework that structures latent space through Dual-pathway Multi-Level discrimination to enhance correspondence between morphological and transcriptional modalities. The multi-scale instance-level discrimination pathway aligns hierarchical histopathology representations extracted at local, neighbor, and global levels with gene expression profiles, capturing scale-aware morphological-transcriptional relationships. In parallel, the cross-level instance-group discrimination pathway enforces structural consistency between individual (image/gene) instances and modality-crossed (gene/image, respectively) groups, strengthening the alignment across modalities. By jointly modeling fine-grained and structural-level discrimination, Gene-DML is able to learn robust cross-modal representations, enhancing both predictive accuracy and generalization across diverse biological contexts. Extensive experiments on public spatial transcriptomics datasets demonstrate that Gene-DML achieves state-of-the-art performance in gene expression prediction. The code and processed datasets are available at https://github.com/YXSong000/Gene-DML.