arXiv:2602.07408cs.AIcs.MA2026-02被引 3

用多智能体协作预测药物扰动下的基因调控,提升准确性与可解释性。

Progressive Multi-Agent Reasoning for Biological Perturbation Prediction

  • 构建多智能体框架,按难度顺序推理并迭代优化知识。
  • 在LINCSQA和PerturbQA上超越基线,小模型也能准确预测复杂过程。
  • 适用于药物研发中的化学扰动预测,特别适合缺乏标注数据的场景。

预测生物扰动引起的基因调控响应需推理其潜在因果关系。尽管大语言模型(LLMs)在该任务中展现潜力,但常因高维扰动结果的纠缠而表现不佳。现有研究主要关注单细胞基因扰动,而对药物研发至关重要的批量细胞化学扰动仍被忽视。为此,我们提出LINCSQA基准,用于预测批量细胞环境中复杂化学扰动下的目标基因调控。进一步提出PBio-Agent多智能体框架,结合难度感知的任务排序与迭代知识精炼。核心洞察是:受相同扰动影响的基因具有共享因果结构,可利用已可靠预测的基因来解释更困难的情况。框架采用富含生物知识图谱的专用智能体,合成智能体整合输出,专业裁判确保逻辑一致性。PBio-Agent在LINCSQA和PerturbQA上均优于现有基线,使小型模型无需额外训练即可预测并解释复杂生物过程。

原文摘要 · Abstract (English)

Predicting gene regulation responses to biological perturbations requires reasoning about underlying biological causalities. While large language models (LLMs) show promise for such tasks, they are often overwhelmed by the entangled nature of high-dimensional perturbation results. Moreover, recent works have primarily focused on genetic perturbations in single-cell experiments, leaving bulk-cell chemical perturbations, which is central to drug discovery, largely unexplored. Motivated by this, we present LINCSQA, a novel benchmark for predicting target gene regulation under complex chemical perturbations in bulk-cell environments. We further propose PBio-Agent, a multi-agent framework that integrates difficulty-aware task sequencing with iterative knowledge refinement. Our key insight is that genes affected by the same perturbation share causal structure, allowing confidently predicted genes to contextualize more challenging cases. The framework employs specialized agents enriched with biological knowledge graphs, while a synthesis agent integrates outputs and specialized judges ensure logical coherence. PBio-Agent outperforms existing baselines on both LINCSQA and PerturbQA, enabling even smaller models to predict and explain complex biological processes without additional training.

生物预测多智能体药物研发因果推理

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