# HyperST: Hierarchical Hyperbolic Learning for Spatial Transcriptomics Prediction

arXiv: https://arxiv.org/abs/2511.22107 · HTML: https://mlsanity.com/paper/2511.22107/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 22 of its 51 references that are in the map.
- First posted on arXiv 27 Nov 2025.

## Builds on (most cited first, 22 of 22)

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Learning Transferable Visual Models From Natural Language Supervision](https://mlsanity.com/paper/2103.00020/) (2021)
- [Representation Learning with Contrastive Predictive Coding](https://mlsanity.com/paper/1807.03748/) (2018)
- [Align before Fuse: Vision and Language Representation Learning with Momentum Distillation](https://mlsanity.com/paper/2107.07651/) (2021)
- [Learning Continuous Hierarchies in the Lorentz Model of Hyperbolic Geometry](https://mlsanity.com/paper/1806.03417/) (2018)
- [Hyperbolic Image Embeddings](https://mlsanity.com/paper/1904.02239/) (2019)
- [Hyperbolic Image-Text Representations](https://mlsanity.com/paper/2304.09172/) (2023)
- [HEST-1k: A Dataset for Spatial Transcriptomics and Histology Image Analysis](https://mlsanity.com/paper/2406.16192/) (2024)
- [Modeling Dense Multimodal Interactions Between Biological Pathways and Histology for Survival Prediction](https://mlsanity.com/paper/2304.06819/) (2023)
- [Spatially Resolved Gene Expression Prediction from H&E Histology Images via Bi-modal Contrastive Learning](https://mlsanity.com/paper/2306.01859/) (2023)
- [Compositional Entailment Learning for Hyperbolic Vision-Language Models](https://mlsanity.com/paper/2410.06912/) (2024)
- [Hyperbolic Deep Learning in Computer Vision: A Survey](https://mlsanity.com/paper/2305.06611/) (2023)
- [Hyperbolic Contrastive Learning for Visual Representations beyond Objects](https://mlsanity.com/paper/2212.00653/) (2022)
- [SlideChat: A Large Vision-Language Assistant for Whole-Slide Pathology Image Understanding](https://mlsanity.com/paper/2410.11761/) (2024)
- [Accurate Spatial Gene Expression Prediction by integrating Multi-resolution features](https://mlsanity.com/paper/2403.07592/) (2024)
- [Diffusion Generative Modeling for Spatially Resolved Gene Expression Inference from Histology Images](https://mlsanity.com/paper/2501.15598/) (2025)
- [Generalizable Whole Slide Image Classification with Fine-Grained Visual-Semantic Interaction](https://mlsanity.com/paper/2402.19326/) (2024)
- [Capturing implicit hierarchical structure in 3D biomedical images with self-supervised hyperbolic representations](https://mlsanity.com/paper/2012.01644/) (2020)
- [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)
- [A Rotated Hyperbolic Wrapped Normal Distribution for Hierarchical Representation Learning](https://mlsanity.com/paper/2205.13371/) (2022)
- [SurvMamba: State Space Model with Multi-grained Multi-modal Interaction for Survival Prediction](https://mlsanity.com/paper/2404.08027/) (2024)

## Abstract (arXiv)

Spatial Transcriptomics (ST) merges the benefits of pathology images and gene expression, linking molecular profiles with tissue structure to analyze spot-level function comprehensively. Predicting gene expression from histology images is a cost-effective alternative to expensive ST technologies. However, existing methods mainly focus on spot-level image-to-gene matching but fail to leverage the full hierarchical structure of ST data, especially on the gene expression side, leading to incomplete image-gene alignment. Moreover, a challenge arises from the inherent information asymmetry: gene expression profiles contain more molecular details that may lack salient visual correlates in histological images, demanding a sophisticated representation learning approach to bridge this modality gap. We propose HyperST, a framework for ST prediction that learns multi-level image-gene representations by modeling the data's inherent hierarchy within hyperbolic space, a natural geometric setting for such structures. First, we design a Multi-Level Representation Extractors to capture both spot-level and niche-level representations from each modality, providing context-aware information beyond individual spot-level image-gene pairs. Second, a Hierarchical Hyperbolic Alignment module is introduced to unify these representations, performing spatial alignment while hierarchically structuring image and gene embeddings. This alignment strategy enriches the image representations with molecular semantics, significantly improving cross-modal prediction. HyperST achieves state-of-the-art performance on four public datasets from different tissues, paving the way for more scalable and accurate spatial transcriptomics prediction.