# Semantic-Aware Subgraph State Space Model for WSI Classification in Histopathology

arXiv: https://arxiv.org/abs/2609.03689 · HTML: https://mlsanity.com/paper/2609.03689/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 30 of its 46 references that are in the map.
- First posted on arXiv 3 Sep 2026.

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

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Learning Transferable Visual Models From Natural Language Supervision](https://mlsanity.com/paper/2103.00020/) (2021)
- [An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale](https://mlsanity.com/paper/2010.11929/) (2020)
- [Segment Anything](https://mlsanity.com/paper/2304.02643/) (2023)
- [Layer Normalization](https://mlsanity.com/paper/1607.06450/) (2016)
- [Mamba: Linear-Time Sequence Modeling with Selective State Spaces](https://mlsanity.com/paper/2312.00752/) (2023)
- [UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction](https://mlsanity.com/paper/1802.03426/) (2018)
- [SAM 2: Segment Anything in Images and Videos](https://mlsanity.com/paper/2408.00714/) (2024)
- [Efficiently Modeling Long Sequences with Structured State Spaces](https://mlsanity.com/paper/2111.00396/) (2021)
- [Grounded Language-Image Pre-training](https://mlsanity.com/paper/2112.03857/) (2021)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [SAM 3: Segment Anything with Concepts](https://mlsanity.com/paper/2511.16719/) (2025)
- [Weisfeiler and Leman Go Neural: Higher-order Graph Neural Networks](https://mlsanity.com/paper/1810.02244/) (2018)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [Combining Recurrent, Convolutional, and Continuous-time Models with Linear State-Space Layers](https://mlsanity.com/paper/2110.13985/) (2021)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [Scaling Vision Transformers to Gigapixel Images via Hierarchical Self-Supervised Learning](https://mlsanity.com/paper/2206.02647/) (2022)
- [DTFD-MIL: Double-Tier Feature Distillation Multiple Instance Learning for Histopathology Whole Slide Image Classification](https://mlsanity.com/paper/2203.12081/) (2022)
- [Whole Slide Images are 2D Point Clouds: Context-Aware Survival Prediction using Patch-based Graph Convolutional Networks](https://mlsanity.com/paper/2107.13048/) (2021)
- [MambaMIL: Enhancing Long Sequence Modeling with Sequence Reordering in Computational Pathology](https://mlsanity.com/paper/2403.06800/) (2024)
- [A graph-transformer for whole slide image classification](https://mlsanity.com/paper/2205.09671/) (2022)
- [Attention-Challenging Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2311.07125/) (2023)
- [Hierarchical Graph Representations in Digital Pathology](https://mlsanity.com/paper/2102.11057/) (2021)
- [CGC-Net: Cell Graph Convolutional Network for Grading of Colorectal Cancer Histology Images](https://mlsanity.com/paper/1909.01068/) (2019)
- [2DMamba: Efficient State Space Model for Image Representation with Applications on Giga-Pixel Whole Slide Image Classification](https://mlsanity.com/paper/2412.00678/) (2024)
- [A Comprehensive Evaluation of Histopathology Foundation Models for Ovarian Cancer Subtype Classification](https://mlsanity.com/paper/2405.09990/) (2024)
- [Combining Graph Neural Network and Mamba to Capture Local and Global Tissue Spatial Relationships in Whole Slide Images](https://mlsanity.com/paper/2406.04377/) (2024)

## Abstract (arXiv)

Histopathological subtyping relies on the recognition of characteristic histological patterns. These patterns may be expressed by individual tissue structures or by the spatial distribution and co-occurrence of multiple structures, and they often span irregularly shaped tissue regions, termed semantic units in this work. However, conventional patch-based representations may fragment such units and fail to explicitly preserve their internal spatial organization, while efficiently modeling relationships among numerous spatially separated units remains challenging. To address these limitations, we propose the Semantic-Aware Subgraph State Space Model (SASG-SSM), a flexible and efficient framework for whole slide image (WSI) classification. Semantic-Aware Subgraphs (SASGs) first approximate irregularly shaped semantic units by adaptively grouping spatially connected patches guided by class-agnostic visual-semantic priors. By representing patches as graph nodes with adjacency edges, SASGs preserve their internal spatial organization rather than treating them as an unordered set. A Subgraph State Space Module (SG-SSM) subsequently combines a graph neural network encoder for intra-subgraph topology encoding with a Mamba-based state space encoder for efficient contextualization across large numbers of subgraphs. This module integrates local structural information within semantic units with global contextual information arising from their distribution and co-occurrence across the WSI, while efficiently modeling a large number of spatially distributed regions. Extensive experiments across four WSI subtyping datasets demonstrate consistent advantages over representative state-of-the-art methods. Further evaluations under small-cohort and few-shot settings demonstrate robustness and data efficiency under limited training data. Code will be released at https://github.com/HLSvois/SASG-SSM.