arXiv:2502.07297cs.LGq-bio.QM2025-02

用AI生成个性化药物影响心电图,提升虚拟临床试验准确性

MM-DADM: Multimodal Drug-Aware Diffusion Model for Virtual Clinical Trials

  • 融合生理知识与因果编码,分离药物效果与人口特征
  • 在8种用药方案中准确率提升6.13%,召回率提升5.89%
  • 适合药物研发、心电图生成与小样本学习研究者

心脏药物研发失败率高,需通过心电图(ECG)生成开展虚拟临床试验以降低风险与成本。现有模型难以兼顾形态真实性和病理灵活性,无法分离人口特征与真实药物效应,且受限于早期数据稀缺。为此,我们提出首个生成个体化药物诱导心电图的多模态药物感知扩散模型(MM-DADM)。该模型引入动态交叉注意力模块,自适应融合外部生理知识,保持形态真实性同时保留复杂病理特征;设计因果特征编码器主动剔除人口噪声,提取纯净药理表征;再通过因果解耦控制网,利用反事实数据增强,在有限临床数据下显式学习内在药理机制。在涵盖8种药物方案的9,443例心电图上实验表明,MM-DADM优于10种先进生成模型,模拟准确率至少提升6.13%,召回率提升5.89%,并有效支持下游分类任务的数据增强。

原文摘要 · Abstract (English)

High failure rates in cardiac drug development necessitate virtual clinical trials via electrocardiogram (ECG) generation to reduce risks and costs. However, existing ECG generation models struggle to balance morphological realism with pathological flexibility, fail to disentangle demographics from genuine drug effects, and are severely bottlenecked by early-phase data scarcity. To overcome these hurdles, we propose the Multimodal Drug-Aware Diffusion Model (MM-DADM), the first generative framework for generating individualized drug-induced ECGs. Specifically, our proposed MM-DADM integrates a Dynamic Cross-Attention (DCA) module that adaptively fuses External Physical Knowledge (EPK) to preserve morphological realism while avoiding the suppression of complex pathological nuances. To resolve feature entanglement, a Causal Feature Encoder (CFE) actively filters out demographic noise to extract pure pharmacological representations. These representations subsequently guide a Causal-Disentangled ControlNet (CDC-Net), which leverages counterfactual data augmentation to explicitly learn intrinsic pharmacological mechanisms despite limited clinical data. Extensive experiments on $9,443$ ECGs across $8$ drug regimens demonstrate that MM-DADM outperforms $10$ state-of-the-art ECG generation models, improving simulation accuracy by at least $6.13\%$ and recall by $5.89\%$, while providing highly effective data augmentation for downstream classification tasks.

心电图生成药物研发扩散模型因果学习

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