# MMAP: A Multi-Magnification and Prototype-Aware Architecture for Predicting Spatial Gene Expression

arXiv: https://arxiv.org/abs/2510.11344 · HTML: https://mlsanity.com/paper/2510.11344/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 12 of its 31 references that are in the map.
- First posted on arXiv 13 Oct 2025.

## Builds on (most cited first, 12 of 12)

- [LoRA: Low-Rank Adaptation of Large Language Models](https://mlsanity.com/paper/2106.09685/) (2021)
- [Whole Slide Images based Cancer Survival Prediction using Attention Guided Deep Multiple Instance Learning Networks](https://mlsanity.com/paper/2009.11169/) (2020)
- [Deep neural network models for computational histopathology: A survey](https://mlsanity.com/paper/1912.12378/) (2019)
- [Virchow2: Scaling Self-Supervised Mixed Magnification Models in Pathology](https://mlsanity.com/paper/2408.00738/) (2024)
- [Spatially Resolved Gene Expression Prediction from H&E Histology Images via Bi-modal Contrastive Learning](https://mlsanity.com/paper/2306.01859/) (2023)
- [Morphological Prototyping for Unsupervised Slide Representation Learning in Computational Pathology](https://mlsanity.com/paper/2405.11643/) (2024)
- [Accurate Spatial Gene Expression Prediction by integrating Multi-resolution features](https://mlsanity.com/paper/2403.07592/) (2024)
- [Histopathology Whole Slide Image Analysis with Heterogeneous Graph Representation Learning](https://mlsanity.com/paper/2307.04189/) (2023)
- [Exemplar Guided Deep Neural Network for Spatial Transcriptomics Analysis of Gene Expression Prediction](https://mlsanity.com/paper/2210.16721/) (2022)
- [DenseNet for Dense Flow](https://mlsanity.com/paper/1707.06316/) (2017)
- [Unsupervised Foundation Model-Agnostic Slide-Level Representation Learning](https://mlsanity.com/paper/2411.13623/) (2024)
- [Bridging Classification and Segmentation in Osteosarcoma Assessment via Foundation and Discrete Diffusion Models](https://mlsanity.com/paper/2501.01932/) (2025)

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

- [Gene Ontology-Guided Hierarchical Spatial Gene Expression Prediction from Histopathology Images](https://mlsanity.com/paper/2608.00405/) (2026)

## Abstract (arXiv)

Spatial Transcriptomics (ST) enables the measurement of gene expression while preserving spatial information, offering critical insights into tissue architecture and disease pathology. Recent developments have explored the use of hematoxylin and eosin (H&E)-stained whole-slide images (WSIs) to predict transcriptome-wide gene expression profiles through deep neural networks. This task is commonly framed as a regression problem, where each input corresponds to a localized image patch extracted from the WSI. However, predicting spatial gene expression from histological images remains a challenging problem due to the significant modality gap between visual features and molecular signals. Recent studies have attempted to incorporate both local and global information into predictive models. Nevertheless, existing methods still suffer from two key limitations: (1) insufficient granularity in local feature extraction, and (2) inadequate coverage of global spatial context. In this work, we propose a novel framework, MMAP (Multi-MAgnification and Prototype-enhanced architecture), that addresses both challenges simultaneously. To enhance local feature granularity, MMAP leverages multi-magnification patch representations that capture fine-grained histological details. To improve global contextual understanding, it learns a set of latent prototype embeddings that serve as compact representations of slide-level information. Extensive experimental results demonstrate that MMAP consistently outperforms all existing state-of-the-art methods across multiple evaluation metrics, including Mean Absolute Error (MAE), Mean Squared Error (MSE), and Pearson Correlation Coefficient (PCC).