融合组织形态与空间基因表达,提升癌症组织分类与生物标志物发现能力
Tissue Classification and Whole-Slide Images Analysis via Modeling of the Tumor Microenvironment and Biological Pathways
- 构建图结构建模组织块间关系,结合形态与分子相似性调整响应强度
- 在前列腺、结直肠、乳腺癌数据集上分类准确率分别提升2.67%~6.29%
- 可自动学习生物通路演化,助力肿瘤微环境解析与潜在标志物挖掘
全切片图像(WSIs)与基因表达谱的自动化整合在精准临床诊断和癌症进展研究中展现出巨大潜力。然而,现有研究多聚焦于单一基因序列或切片级别分类任务,对空间转录组学和局部图像块层面的应用关注较少。为此,我们提出一种多模态网络BioMorphNet,自动整合组织形态特征与空间基因表达,支持组织分类与差异基因分析。针对形态特征,BioMorphNet构建图模型以刻画目标图像块与其邻域的关系,并根据形态与分子水平的相似性动态调节响应强度,更精准表征肿瘤微环境。在多模态交互方面,基于预定义通路数据库从空间转录组数据中提取临床通路特征,作为连接组织形态与基因表达的桥梁;同时设计一种新型可学习通路模块,自动模拟生物通路形成过程,提供对现有临床通路的补充表示。相较于最新的形态-基因多模态方法,BioMorphNet在前列腺癌、结直肠癌和乳腺癌数据集上的平均分类指标分别提升2.67%、5.48%和6.29%。该模型不仅能精确分类WSI中的组织类型以支持肿瘤定位,还能基于预测置信度分析不同组织类别间的差异基因表达,有助于发现潜在肿瘤生物标志物。
原文摘要 · Abstract (English)
Automatic integration of whole slide images (WSIs) and gene expression profiles has demonstrated substantial potential in precision clinical diagnosis and cancer progression studies. However, most existing studies focus on individual gene sequences and slide level classification tasks, with limited attention to spatial transcriptomics and patch level applications. To address this limitation, we propose a multimodal network, BioMorphNet, which automatically integrates tissue morphological features and spatial gene expression to support tissue classification and differential gene analysis. For considering morphological features, BioMorphNet constructs a graph to model the relationships between target patches and their neighbors, and adjusts the response strength based on morphological and molecular level similarity, to better characterize the tumor microenvironment. In terms of multimodal interactions, BioMorphNet derives clinical pathway features from spatial transcriptomic data based on a predefined pathway database, serving as a bridge between tissue morphology and gene expression. In addition, a novel learnable pathway module is designed to automatically simulate the biological pathway formation process, providing a complementary representation to existing clinical pathways. Compared with the latest morphology gene multimodal methods, BioMorphNet's average classification metrics improve by 2.67%, 5.48%, and 6.29% for prostate cancer, colorectal cancer, and breast cancer datasets, respectively. BioMorphNet not only classifies tissue categories within WSIs accurately to support tumor localization, but also analyzes differential gene expression between tissue categories based on prediction confidence, contributing to the discovery of potential tumor biomarkers.
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