比较三种生物通路模型对癌症治疗和生存预测的性能,发现生存预测差异显著。
TRAPS: Treatment-Assignment Prediction via Pathway-informed Stratification

- 基于通路活性构建共享表示,联合预测治疗暴露与短期生存
- 乳腺癌生存预测中稀疏层级模型表现最优,AUC提升0.14且显著
- 治疗暴露预测无明显优劣,辐射治疗预测整体较弱
癌症治疗涉及多重临床结局的决策,但现有通路引导的深度学习模型多独立评估,其相对优势不明确。本文构建统一基准,对比三种生物信息架构(BINN、GraphPath、PATH)在五个TCGA癌症队列(共2,622名患者)中预测靶向治疗(TMT)、放疗(RT)暴露及六月总生存率(OS)的表现。所有模型基于相同的通路活性评分进行联合预测,采用相同分层交叉验证与五次重复拆分+配对自举检验。在控制条件下,多数架构差异未超过95%置信区间,表明孤立评估的排名不可靠。唯一例外是生存预测:稀疏层次的BINN在乳腺癌中显著优于两种图模型,最高提升0.14的AUROC(p ≤ 0.01),并在肺癌和前列腺癌中领先。治疗暴露方面,前列腺癌的TMT预测性能最佳(各模型约0.80 AUROC),但无显著差异;所有模型对放疗预测均较弱,暗示其决定因素更偏向临床而非转录组特征。总体而言,在统一评估下,架构选择影响有限,而短期生存预测最能区分不同模型性能。
原文摘要 · Abstract (English)
Cancer treatment involves decisions across multiple clinical outcomes, yet pathway-informed deep learning models are typically evaluated in isolation, making their relative benefits unclear. We present a harmonized benchmark of three biologically informed architectures, BINN, GraphPath, and PATH, for predicting treatment exposure and short-term survival across five TCGA cancer cohorts comprising 2,622 patients represented by Reactome pathway activity scores. Treatment labels indicate recorded exposure in TCGA rather than therapeutic response. All models jointly predict targeted molecular therapy (TMT), radiation therapy (RT), and six-month overall survival (OS) from a shared pathway representation and are evaluated on identical stratified folds using five repeated splits and paired-bootstrap testing. Under this controlled evaluation, most differences between architectures fall within 95 percent confidence intervals, indicating that rankings suggested by isolated evaluations are largely not statistically resolved. The main exception is survival prediction: the sparse-hierarchy BINN significantly outperforms both graph models on breast-cancer OS, with an AUROC improvement of up to 0.14 and p less than or equal to 0.01, and leads on lung and prostate OS. For treatment exposure, TMT is best discriminated in prostate cancer, with AUROC approximately 0.80 for all models, but no architecture significantly outperforms another on any TMT cohort. RT prediction remains weak across models, suggesting that its determinants may be more clinical than transcriptomic. Overall, architecture choice has limited impact under a unified evaluation, while short-term survival provides the clearest differentiation among pathway-informed models.
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