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arXiv 提交日期: 2026-07-06
📄 Abstract - Predicting Therapeutic Outcome via Aligning Patient-Specific Knowledge Graph and Gene-Level Perturbation Representations

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.

顶级标签: medical machine learning
详细标签: drug response prediction knowledge graph gene perturbation contrastive learning precision oncology 或 搜索:

通过对齐患者特定知识图谱与基因层面扰动表征来预测治疗效果 / Predicting Therapeutic Outcome via Aligning Patient-Specific Knowledge Graph and Gene-Level Perturbation Representations


1️⃣ 一句话总结

本研究提出一种名为PREDIKTOR的新型计算框架,通过将每位患者的个性化基因调控网络与药物诱导的基因表达变化模拟相结合,更准确地预测癌症患者对特定药物的治疗反应,并在多个数据集上显著优于现有方法。

源自 arXiv: 2607.04557