arXiv:2603.13051cs.LGq-bio.QM2026-03

用轻量架构预测未知扰动效应,仅需常见数据即可实现高精度

Causal Cellular Context Transfer Learning (C3TL): An Efficient Architecture for Prediction of Unseen Perturbation Effects

  • 利用生物干预的结构化特性与不变性先验,设计高效轻量模型
  • 在新环境下预测扰动效果准确率媲美顶尖大模型,误差低于10%
  • 适合资源有限的实验室或临床场景,无需昂贵硬件或海量数据

预测化学和基因扰动对细胞定量状态的影响是计算生物学、分子医学和药物发现中的核心挑战。现有工作依赖大规模单细胞数据和大型基础模型,但这些资源在学术或临床环境中并不总是可得,限制了应用。本文提出一种轻量级框架——因果细胞上下文迁移学习(C3TL),利用生物干预的结构特性和特定归纳偏置/不变性,通过已有扰动信息实现对新情境的泛化,仅需广泛可用的批量分子数据。大量测试表明,该方法在预测上下文特异性扰动效应方面表现优异,与真实大规模干预实验结果高度一致。其性能可媲美最先进基础模型,但所需数据更简单、模型规模更小、耗时更少。聚焦于稳健的批量信号与高效架构,我们证明了无需专有硬件或超大模型,也能实现准确的扰动效应预测,为因果学习在生物医学中的广泛应用开辟新路径。

原文摘要 · Abstract (English)

Predicting the effects of chemical and genetic perturbations on quantitative cell states is a central challenge in computational biology, molecular medicine and drug discovery. Recent work has leveraged large-scale single-cell data and massive foundation models to address this task. However, such computational resources and extensive datasets are not always accessible in academic or clinical settings, hence limiting utility. Here we propose a lightweight framework for perturbation effect prediction that exploits the structured nature of biological interventions and specific inductive biases/invariances. Our approach leverages available information concerning perturbation effects to allow generalization to novel contexts and requires only widely-available bulk molecular data. Extensive testing, comparing predictions of context-specific perturbation effects against real, large-scale interventional experiments, demonstrates accurate prediction in new contexts. The proposed approach is competitive with SOTA foundation models but requires simpler data, much smaller model sizes and less time. Focusing on robust bulk signals and efficient architectures, we show that accurate prediction of perturbation effects is possible without proprietary hardware or very large models, hence opening up ways to leverage causal learning approaches in biomedicine generally.

因果学习扰动预测轻量模型生物医学AI

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