用病理图像和基因数据联合预测空间基因表达,提升精度。
Dual-Path Knowledge-Augmented Contrastive Alignment Network for Spatially Resolved Transcriptomics
- 双路径结构融合图像与基因信息,引入外部基因数据库增强语义理解。
- 对比学习与监督学习统一训练,无需样本检索,提升泛化能力。
- 适合生物医学研究者,尤其关注肿瘤组织异质性分析的团队。
空间转录组学(ST)可在保留组织空间位置的前提下测量基因表达,揭示局部表达模式与组织异质性,对疾病机制研究至关重要。但其高昂成本促使研究者尝试从全切片图像预测空间基因表达。现有方法仍存在高阶生物上下文利用不足、依赖样本检索、跨模态对齐不充分等问题。为此,我们提出DKAN——一种双路径知识增强对比对齐网络,通过生物引导方式整合病理图像与基因表达数据以预测空间基因表达。具体而言,设计基因语义表示模块,利用外部基因数据库提供额外生物学洞察;采用统一的一阶段对比学习范式,结合对比学习与监督学习,消除对样本检索的依赖,并引入自适应加权机制;进一步提出双路径对比对齐模块,以基因语义特征为动态跨模态协调器,实现异构特征的有效融合。在三个公开的ST数据集上进行的大量实验表明,DKAN显著优于当前最优模型,建立了新的基准,为生物与临床研究提供了有力工具。
原文摘要 · Abstract (English)
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.
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