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

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Main Authors: Zhang, Wei, Chu, Jiajun, Liu, Xinci, Tong, Chen, Li, Xinyue
Format: Preprint
Published: 2025
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author Zhang, Wei
Chu, Jiajun
Liu, Xinci
Tong, Chen
Li, Xinyue
author_facet Zhang, Wei
Chu, Jiajun
Liu, Xinci
Tong, Chen
Li, Xinyue
contents 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.
format Preprint
id arxiv_https___arxiv_org_abs_2511_17685
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Dual-Path Knowledge-Augmented Contrastive Alignment Network for Spatially Resolved Transcriptomics
Zhang, Wei
Chu, Jiajun
Liu, Xinci
Tong, Chen
Li, Xinyue
Quantitative Methods
Artificial Intelligence
Computer Vision and Pattern Recognition
Machine Learning
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.
title Dual-Path Knowledge-Augmented Contrastive Alignment Network for Spatially Resolved Transcriptomics
topic Quantitative Methods
Artificial Intelligence
Computer Vision and Pattern Recognition
Machine Learning
url https://arxiv.org/abs/2511.17685