arXiv:2509.07850cs.LG2025-09被引 1

用预训练模型指导癌症药物组合初筛,提升个性化治疗效率。

Addressing the Cold-Start Problem for Personalized Combination Drug Screening

  • 基于历史数据构建深度学习模型,生成药物组合嵌入与剂量重要性评分。
  • 通过聚类确保初始实验组合功能多样,按历史信息优先选择关键剂量。
  • 在大规模数据集上验证,显著优于基线方法,适合早期个性化药筛场景。

个性化癌症治疗需探索海量药物与剂量组合,但全面实验不可行。患者源性模型支持高通量体外筛选,但实验数量受限。同时,狭窄的治疗窗使分子谱分析(如RNA-seq)难以用于预测药效。这带来严峻的冷启动问题:如何在无患者先验信息时,选出最能提供信息的初始组合?本文提出一种策略,利用基于历史药效数据的预训练深度学习模型,生成药物组合嵌入和剂量重要性评分,实现有依据的初始实验选择。通过药物嵌入聚类保证组合功能多样性,并结合剂量加权机制,优先选择历史中信息量大的剂量。在大规模药物组合数据集上的回溯模拟表明,该方法显著提升初始筛选效率,为个性化药物组合筛选的早期决策提供可行路径。

原文摘要 · Abstract (English)

Personalizing combination therapies in oncology requires navigating an immense space of possible drug and dose combinations, a task that remains largely infeasible through exhaustive experimentation. Recent developments in patient-derived models have enabled high-throughput ex vivo screening, but the number of feasible experiments is limited. Further, a tight therapeutic window makes gathering molecular profiling information (e.g. RNA-seq) impractical as a means of guiding drug response prediction. This leads to a challenging cold-start problem: how do we select the most informative combinations to test early, when no prior information about the patient is available? We propose a strategy that leverages a pretrained deep learning model built on historical drug response data. The model provides both embeddings for drug combinations and dose-level importance scores, enabling a principled selection of initial experiments. We combine clustering of drug embeddings to ensure functional diversity with a dose-weighting mechanism that prioritizes doses based on their historical informativeness. Retrospective simulations on large-scale drug combination datasets show that our method substantially improves initial screening efficiency compared to baselines, offering a viable path for more effective early-phase decision-making in personalized combination drug screens.

药物组合冷启动深度学习个性化医疗

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