arXiv:2604.16685cs.LGcs.AI2026-04被引 2

用基因共享嵌入+患者特异性调制,提升癌症预后预测精度

Graph Transformer-Based Pathway Embedding for Cancer Prognosis

论文配图:Graph Transformer-Based Pathway Embedding for Cancer Prognosis
图 1 · 摘自论文原文
  • 基于共享基因嵌入动态调整,融合拷贝数变异与突变信息
  • 在泛癌转移预测中F1达0.8766,较当前最优提升8.8%
  • 可识别关键通路并揭示疾病状态下的通路重编程机制

由于患者间分子组学数据的高度异质性,癌症进展的精准预测仍具挑战。现有生物信息模型虽提升了可解释性,但基因表征构建方式存在局限:传统分层模型直接映射原始输入,集成框架则依赖患者层面信号的简单聚合,难以显式学习基因的共享基础表示,限制了下游通路嵌入的表达能力与生物学准确性。为此,我们提出PATH——一种基于调制的、患者条件化的基因嵌入策略。该方法从每个基因的共享基础嵌入出发,保持群体内稳定的生物学身份,并通过患者特异的拷贝数变异(CNV)和突变信号动态调整。此设计既捕捉个体分子差异,又维持对基因本身的稳定潜在理解。我们将PATH集成至图注意力网络,通过通路引导的注意力建模生物关联通路间的交互。在泛癌转移预测任务中,PATH取得0.8766的F1分数,较当前最优多组学基准提升8.8%。除预测性能优越外,该方法还能识别具有生物学意义的通路,并关键性揭示疾病状态特异的通路重编程现象,为癌症进展中的通路-通路动态互作提供新见解。

原文摘要 · Abstract (English)

Accurate prediction of cancer progression remains a challenge due to the high heterogeneity of molecular omics data across patients. While biologically informed models have improved the interpretability of these predictions, a persistent limitation lies in how they encode individual genes to construct pathway representations. Existing hierarchical models typically derive gene features by directly mapping raw molecular inputs, whereas integration frameworks often rely on simple statistical aggregations of patient-level signals. These approaches often fail to explicitly learn a shared base representation for each gene, thereby limiting the expressiveness and biological accuracy of downstream pathway embeddings. To address this, we introduce PATH, a modulation-based, patient-conditioned gene embedding strategy. PATH represents a paradigm shift by starting from a shared base embedding for each gene, preserving a stable biological identity across the population, and then dynamically adapting it using patient-specific copy number variation (CNV) and mutation signals. This allows the model to capture subtle individual molecular variations while maintaining a consistent latent understanding of the gene itself. We integrate PATH into a graph transformer framework that models interactions among biologically connected pathways through pathway-guided attention. Across pancancer metastasis prediction, PATH achieves an F1 score of 0.8766, representing an 8.8 percent improvement over the current SOTA multi-omics benchmarks. Beyond superior predictive accuracy, our approach identifies biologically meaningful pathways and, crucially, reveals disease-state-specific pathway rewiring, offering new insights into the evolving pathway-pathway interactions that drive cancer progression.

癌症预后图注意力通路分析

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