# Dual-Path Knowledge-Augmented Contrastive Alignment Network for Spatially Resolved Transcriptomics

arXiv: https://arxiv.org/abs/2511.17685 · HTML: https://mlsanity.com/paper/2511.17685/

## Key facts

- Cited by 2 papers in the map (data through 14 Oct 2026).
- Builds on 15 of its 34 references that are in the map.
- First posted on arXiv 21 Nov 2025.

## Builds on (most cited first, 15 of 15)

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale](https://mlsanity.com/paper/2010.11929/) (2020)
- [Representation Learning with Contrastive Predictive Coding](https://mlsanity.com/paper/1807.03748/) (2018)
- [Densely Connected Convolutional Networks](https://mlsanity.com/paper/1608.06993/) (2016)
- [DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learning](https://mlsanity.com/paper/2501.12948/) (2025)
- [BioBERT: a pre-trained biomedical language representation model for biomedical text mining](https://mlsanity.com/paper/1901.08746/) (2019)
- [BioGPT: Generative Pre-trained Transformer for Biomedical Text Generation and Mining](https://mlsanity.com/paper/2210.10341/) (2022)
- [Self supervised contrastive learning for digital histopathology](https://mlsanity.com/paper/2011.13971/) (2020)
- [Accurate Spatial Gene Expression Prediction by integrating Multi-resolution features](https://mlsanity.com/paper/2403.07592/) (2024)
- [Exemplar Guided Deep Neural Network for Spatial Transcriptomics Analysis of Gene Expression Prediction](https://mlsanity.com/paper/2210.16721/) (2022)
- [Adaptive Supervised PatchNCE Loss for Learning H&E-to-IHC Stain Translation with Inconsistent Groundtruth Image Pairs](https://mlsanity.com/paper/2303.06193/) (2023)
- [Multimodal contrastive learning for spatial gene expression prediction using histology images](https://mlsanity.com/paper/2407.08216/) (2024)
- [SEPAL: Spatial Gene Expression Prediction from Local Graphs](https://mlsanity.com/paper/2309.01036/) (2023)
- [M2OST: Many-to-one Regression for Predicting Spatial Transcriptomics from Digital Pathology Images](https://mlsanity.com/paper/2409.15092/) (2024)
- [Spatial Transcriptomics Analysis of Zero-shot Gene Expression Prediction](https://mlsanity.com/paper/2401.14772/) (2024)

## Built on by (most cited first, 2 of 2)

- [Breaking the Resource Wall: Geometry-Guided Sequence Modeling for Efficient Semantic Segmentation](https://mlsanity.com/paper/2604.23399/) (2026)
- [SpaFactor: Lightweight Spatial Context-Aware Gene Program Modeling for Histology-to-Transcriptomics Inference](https://mlsanity.com/paper/2609.28563/) (2026)

## Abstract (arXiv)

Spatial Transcriptomics (ST) is a technology that measures gene expression profiles within tissue sections while retaining spatial context. It reveals localized gene expression patterns and tissue heterogeneity, both of which are essential for understanding disease etiology. However, its high cost has driven efforts to predict spatial gene expression from whole slide images. Despite recent advancements, current methods still face significant limitations, such as under-exploitation of high-level biological context, over-reliance on exemplar retrievals, and inadequate alignment of heterogeneous modalities. To address these challenges, we propose DKAN, a novel Dual-path Knowledge-Augmented contrastive alignment Network that predicts spatially resolved gene expression by integrating histopathological images and gene expression profiles through a biologically informed approach. Specifically, we introduce an effective gene semantic representation module that leverages the external gene database to provide additional biological insights, thereby enhancing gene expression prediction. Further, we adopt a unified, one-stage contrastive learning paradigm, seamlessly combining contrastive learning and supervised learning to eliminate reliance on exemplars, complemented with an adaptive weighting mechanism. Additionally, we propose a dual-path contrastive alignment module that employs gene semantic features as dynamic cross-modal coordinators to enable effective heterogeneous feature integration. Through extensive experiments across three public ST datasets, DKAN demonstrates superior performance over state-of-the-art models, establishing a new benchmark for spatial gene expression prediction and offering a powerful tool for advancing biological and clinical research.