整合基因、蛋白与病理图像,构建生物层级融合模型提升癌症预后预测。
Advancing Cancer Prognosis with Hierarchical Fusion of Genomic, Proteomic and Pathology Imaging Data from a Systems Biology Perspective
- 从系统生物学出发,分层建模基因→蛋白→图像的生物演化路径。
- 在五个数据集上显著优于现有方法,生存预测准确率大幅提升。
- 适合肿瘤生物信息学、精准医疗领域研究者参考。
为提升癌症预后预测精度,现有研究多聚焦于整合基因组数据与组织病理图像的多模态生存分析。然而,当前方法忽视了蛋白质组作为连接基因变异与组织形态特征的中间桥梁作用,且其提供的互补生物学信息对生存预测至关重要。这一生物学现实暴露了现有整合分析的架构缺陷:对异构数据采用扁平化融合,未能捕捉其内在生物层次结构。为此,我们提出HFGPI(Hierarchical Fusion of Genomic, Proteomic, and Pathology Imaging data),从系统生物学视角建模基因到蛋白再到病理图像的生物进展过程。具体而言,提出Molecular Tokenizer,通过身份嵌入与表达谱融合生成基因与蛋白的生物学感知表征;设计Gene-Regulated Protein Fusion(GRPF),利用图感知交叉注意力与结构保持对齐,显式建模基因-蛋白调控关系并生成基因调控蛋白表征;提出Protein-Guided Hypergraph Learning(PGHL),建立蛋白与图像块间的关联,通过超图卷积捕获高阶蛋白-形态关系。最终特征在层级间逐步融合,实现精准生存结局预测。在五个基准数据集上的大量实验表明,HFGPI显著优于现有先进方法。
原文摘要 · Abstract (English)
To enhance the precision of cancer prognosis, recent research has increasingly focused on multimodal survival methods by integrating genomic data and histology images. However, current approaches overlook the fact that the proteome serves as an intermediate layer bridging genomic alterations and histopathological features while providing complementary biological information essential for survival prediction. This biological reality exposes another architectural limitation: existing integrative analysis studies fuse these heterogeneous data sources in a flat manner that fails to capture their inherent biological hierarchy. To address these limitations, we propose HFGPI, a hierarchical fusion framework that models the biological progression from genes to proteins to histology images from a systems biology perspective. Specifically, we introduce Molecular Tokenizer, a molecular encoding strategy that integrates identity embeddings with expression profiles to construct biologically informed representations for genes and proteins. We then develop Gene-Regulated Protein Fusion (GRPF), which employs graph-aware cross-attention with structure-preserving alignment to explicitly model gene-protein regulatory relationships and generate gene-regulated protein representations. Additionally, we propose Protein-Guided Hypergraph Learning (PGHL), which establishes associations between proteins and image patches, leveraging hypergraph convolution to capture higher-order protein-morphology relationships. The final features are progressively fused across hierarchical layers to achieve precise survival outcome prediction. Extensive experiments on five benchmark datasets demonstrate the superiority of HFGPI over state-of-the-art methods.
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