arXiv:2607.04557cs.LGcs.AI2026-07中稿 · KDD被引 1

通过融合患者特异性网络与药物扰动表示,提升癌症治疗反应预测准确性。

Predicting Therapeutic Outcome via Aligning Patient-Specific Knowledge Graph and Gene-Level Perturbation Representations

论文配图:Predicting Therapeutic Outcome via Aligning Patient-Specific Knowledge Graph and Gene-Level Perturbation Representations
图 1 · 摘自论文原文
  • 构建患者特异基因调控网络与药物扰动模拟表征,双视角对齐预测疗效。
  • 在TCGA上超越主流方法,在I-SPY2零样本迁移中提升AUROC 5.6%。
  • 结果可解释,能恢复已知机制,适合精准肿瘤学临床决策支持。

从治疗前转录组准确预测患者特异性治疗反应,受限于匹配的临床响应标签和治疗后分子谱的稀缺性。现有预临床迁移学习模型虽可模拟药物诱导的表达变化,但可解释性差且不稳定;知识图谱方法提供机制背景,却静态且无法捕捉药物诱导的转录组动态变化。本文提出PREDIKTOR,一种以患者为中心的多视图框架,将个性化网络视图与可迁移的转录组扰动视图对齐,以预测临床药物反应。针对每位患者,基于肿瘤表达数据使用DysRegNet构建个体化基因调控网络,并融合DrugBank中的药物-靶点链接;图神经编码器生成以药物为中心、机制驱动的嵌入表示。同时,采用在LINCS L1000上预训练的条件特异性基因-基因注意力模型,生成同一患者-药物对的模拟后扰动转录组谱。通过类似CLIP的对比目标,在共享潜在空间中对齐两视图,加入药物上下文硬负例,最后拼接表示进行端到端响应分类。在TCGA上,PREDIKTOR在患者、药物和组织分割评估中持续优于现有最优方法,并在I-SPY2试验中实现零样本迁移,使AUROC提升5.6%。对齐嵌入产生稳定的基因与通路归因,复现已知机制,支持可操作且可解释的精准肿瘤学应用。

原文摘要 · Abstract (English)

Accurate prediction of patient-specific therapeutic response from pre-treatment transcriptomes is hindered by the scarcity of matched clinical response labels and post-treatment molecular profiles. Preclinical transfer-learning models can simulate drug-induced expression changes but are often hard to interpret and unstable, whereas knowledge-graph methods provide mechanistic context yet remain static and fail to capture drug-induced transcriptomic perturbation dynamics. We propose PREDIKTOR, a patient-centered multi-view framework that aligns a personalized network view with a transferable transcriptomic perturbation view to predict clinical drug response. For each patient, we construct an individualized gene regulatory network from tumor expression using DysRegNet and augment it with drug-target links from DrugBank; a graph neural encoder yields a drug-centric, mechanistically grounded embedding. In parallel, a frozen condition-specific gene-gene attention model pretrained on LINCS L1000 generates a simulated post-perturbation transcriptomic profile for the same patient-drug pair. We align the two views in a shared latent space via a CLIP-style contrastive objective with drug-context hard negatives, then concatenate the representations for end-to-end response classification. On TCGA, PREDIKTOR consistently outperforms state-of-the-art baselines under patient-, drug-, and tissue-split evaluations, and transfers zero-shot to the I-SPY2 trial, improving AUROC by 5.6% over competing methods. The aligned embeddings yield stable gene and pathway attributions that recover known mechanisms, supporting actionable and interpretable precision oncology.

精准医疗知识图谱药物反应预测GNN

Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。