用图神经网络分析癌症基因数据,发现浅层模型更准且可解释。
Hierarchical Pooling and Explainability in Graph Neural Networks for Tumor and Tissue-of-Origin Classification Using RNA-seq Data
- 通过多层池化将基因聚类为超节点,逐步降维保留生物关系
- 单层池化时F1-macro达0.978,层数增加反致过平滑、性能下降
- 梯度方法能识别已知癌基因和关键通路,适合生物机制探索
本研究利用带有层级池化的图神经网络(GNN)和多卷积层对RNA-seq数据进行癌症分类。结合癌症基因组图谱(TCGA)的基因表达数据与预构建的STRING蛋白互作网络,用于组织来源分类及正常与肿瘤样本区分。模型采用二阶切比雪夫图卷积(K=2)与加权池化层,在多级粗化中聚合基因簇为‘超节点’,实现降维同时保留有意义的交互。通过显著性方法解释模型,识别出与癌症相关的关键基因和生物过程。结果表明,增加卷积与池化层数未提升分类性能;单层池化达到最高F1-macro分数0.978,层数增多导致过平滑和性能下降。但模型可通过梯度方法实现高可解释性,识别已知癌基因并揭示富集的生物过程,其层级结构可用于设计新型可解释架构。尽管更深的GNN未改善性能,但层级池化提供了对肿瘤生物学的深刻洞察,表明GNN在癌症生物标志物发现与解析中具有潜力。
原文摘要 · Abstract (English)
This study explores the use of graph neural networks (GNNs) with hierarchical pooling and multiple convolution layers for cancer classification based on RNA-seq data. We combine gene expression data from The Cancer Genome Atlas (TCGA) with a precomputed STRING protein-protein interaction network to classify tissue origin and distinguish between normal and tumor samples. The model employs Chebyshev graph convolutions (K=2) and weighted pooling layers, aggregating gene clusters into 'supernodes' across multiple coarsening levels. This approach enables dimensionality reduction while preserving meaningful interactions. Saliency methods were applied to interpret the model by identifying key genes and biological processes relevant to cancer. Our findings reveal that increasing the number of convolution and pooling layers did not enhance classification performance. The highest F1-macro score (0.978) was achieved with a single pooling layer. However, adding more layers resulted in over-smoothing and performance degradation. However, the model proved highly interpretable through gradient methods, identifying known cancer-related genes and highlighting enriched biological processes, and its hierarchical structure can be used to develop new explainable architectures. Overall, while deeper GNN architectures did not improve performance, the hierarchical pooling structure provided valuable insights into tumor biology, making GNNs a promising tool for cancer biomarker discovery and interpretation
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