# Tissue Classification and Whole-Slide Images Analysis via Modeling of the Tumor Microenvironment and Biological Pathways

arXiv: https://arxiv.org/abs/2601.08336 · HTML: https://mlsanity.com/paper/2601.08336/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 7 of its 44 references that are in the map.
- First posted on arXiv 13 Jan 2026.

## Builds on (most cited first, 7 of 7)

- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Pathomic Fusion: An Integrated Framework for Fusing Histopathology and Genomic Features for Cancer Diagnosis and Prognosis](https://mlsanity.com/paper/1912.08937/) (2019)
- [Multimodal Optimal Transport-based Co-Attention Transformer with Global Structure Consistency for Survival Prediction](https://mlsanity.com/paper/2306.08330/) (2023)
- [Handcrafted Histological Transformer (H2T): Unsupervised Representation of Whole Slide Images](https://mlsanity.com/paper/2202.07001/) (2022)
- [HEALNet: Multimodal Fusion for Heterogeneous Biomedical Data](https://mlsanity.com/paper/2311.09115/) (2023)
- [Unsupervised Mutual Transformer Learning for Multi-Gigapixel Whole Slide Image Classification](https://mlsanity.com/paper/2305.02032/) (2023)

## Abstract (arXiv)

Automatic integration of whole slide images (WSIs) and gene expression profiles has demonstrated substantial potential in precision clinical diagnosis and cancer progression studies. However, most existing studies focus on individual gene sequences and slide level classification tasks, with limited attention to spatial transcriptomics and patch level applications. To address this limitation, we propose a multimodal network, BioMorphNet, which automatically integrates tissue morphological features and spatial gene expression to support tissue classification and differential gene analysis. For considering morphological features, BioMorphNet constructs a graph to model the relationships between target patches and their neighbors, and adjusts the response strength based on morphological and molecular level similarity, to better characterize the tumor microenvironment. In terms of multimodal interactions, BioMorphNet derives clinical pathway features from spatial transcriptomic data based on a predefined pathway database, serving as a bridge between tissue morphology and gene expression. In addition, a novel learnable pathway module is designed to automatically simulate the biological pathway formation process, providing a complementary representation to existing clinical pathways. Compared with the latest morphology gene multimodal methods, BioMorphNet's average classification metrics improve by 2.67%, 5.48%, and 6.29% for prostate cancer, colorectal cancer, and breast cancer datasets, respectively. BioMorphNet not only classifies tissue categories within WSIs accurately to support tumor localization, but also analyzes differential gene expression between tissue categories based on prediction confidence, contributing to the discovery of potential tumor biomarkers.