arXiv:2608.12219cs.LG2026-08

ScreenShot用少量数据预测药物组合疗效,无需分子检测和调参。

ScreenShot: A Foundation Model for Few-Shot Combination Drug Screening

论文配图:ScreenShot: A Foundation Model for Few-Shot Combination Drug Screening
图 1 · 摘自论文原文
  • 基于40个数据集预训练的分层Transformer,直接处理功能测量数据
  • 少样本下预测准确率超越所有基线,能识别选择性有效疗法
  • 可生成实验设计建议,用三分之一预算达到同等筛选效果

联合用药可降低单一药物耐药风险,但组合筛选因搜索空间庞大而成本高、耗时长且技术上难实现。现有预测模型通常需每样本分子谱分析及特定队列训练,限制了在时间与组织稀缺情况下的应用。为此,我们提出ScreenShot——一个在40个药物筛选数据集(覆盖3,700种药物、6,000个生物样本)上预训练的分层Transformer,其架构模仿筛选数据的嵌套结构。给定新患者少量观测数据,ScreenShot通过上下文学习直接预测样本对组合疗法的反应,无需微调或分子谱分析。在四个保留数据集上,ScreenShot在预测精度和有效治疗识别上均优于所有基线。其内部表示可用于实验设计:我们利用它构建加权k-means++主动学习策略,仅用三分之一预算即可达到均匀筛选的命中率。源码与交互式仪表板:https://github.com/tansey-lab/screenshot。

原文摘要 · Abstract (English)

Treating patients with combinations of drugs reduces the risk of resistance to any individual drug. Finding effective combinations is difficult because the large search space makes combinatorial screens prohibitively expensive, time consuming, and often technically infeasible. Predictive models can fill this gap, yet existing methods typically require molecular profiling of each sample and per-cohort training, limiting their applicability when time and tissue are scarce. To address this challenge, we introduce ScreenShot, a hierarchical transformer pretrained on 40 drug screening datasets covering 3,700 drugs and 6,000 biological samples, whose architecture mirrors the nested structure of screening data. Given a few-shot context of observations from a new patient, ScreenShot predicts the response of the sample to combination therapies through in-context learning, operating directly on functional measurements with no fine-tuning and no molecular profiling. On four held-out datasets, ScreenShot outperforms all baselines in both prediction accuracy and identification of selectively effective treatments. ScreenShot's internal representations are directly useful for experimental design: we use them to drive a weighted k-means++ active learning strategy that selects which experiments to run, achieving the same hit detection as uniform screening with a third of the budget. Source code and interactive dashboard: https://github.com/tansey-lab/screenshot.

药物组合少样本学习主动学习

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