arXiv:2510.21337cs.CV2025-10

FORM可预测药物扰动下细胞三维形态变化,助力虚拟细胞构建。

Morphologically Intelligent Perturbation Prediction with FORM

  • 用多通道VQGAN学习细胞3D形状的紧凑表示,结合扩散模型模拟形态演化
  • 在6.5万+个3D细胞数据上训练,支持无条件生成与条件模拟
  • 可预测信号通路活性、组合扰动效果,适合药物研发与细胞生物学研究

理解细胞对环境刺激的响应是生物医学研究与药物开发的核心挑战。现有计算框架多局限于二维表征,难以捕捉扰动下细胞形态的复杂性,制约了虚拟细胞模型的准确性。本文提出FORM,一种用于预测扰动诱导的三维细胞结构变化的机器学习框架。FORM包含两个组件:一个通过新型多通道VQGAN端到端训练的形态编码器,用于学习细胞形状的紧凑3D表示;一个基于扩散模型的扰动轨迹模块,用于捕捉形态在不同扰动条件下的演化过程。该模型在超过6.5万个多荧光3D细胞体积数据集上训练,涵盖多种化学和基因扰动。FORM支持无条件形态生成与条件扰动状态模拟。除生成外,还能预测下游信号活性,模拟组合扰动效应,并建模未见扰动状态间的动态过渡。为评估性能,我们引入MorphoEval基准套件,从结构、统计与生物维度量化扰动引起的形态变化。FORM与MorphoEval共同推动高分辨率预测模拟的发展,实现形态、扰动与功能的三维关联。

原文摘要 · Abstract (English)

Understanding how cells respond to external stimuli is a central challenge in biomedical research and drug development. Current computational frameworks for modelling cellular responses remain restricted to two-dimensional representations, limiting their capacity to capture the complexity of cell morphology under perturbation. This dimensional constraint poses a critical bottleneck for the development of accurate virtual cell models. Here, we present FORM, a machine learning framework for predicting perturbation-induced changes in three-dimensional cellular structure. FORM consists of two components: a morphology encoder, trained end-to-end via a novel multi-channel VQGAN to learn compact 3D representations of cell shape, and a diffusion-based perturbation trajectory module that captures how morphology evolves across perturbation conditions. Trained on a large-scale dataset of over 65,000 multi-fluorescence 3D cell volumes spanning diverse chemical and genetic perturbations, FORM supports both unconditional morphology synthesis and conditional simulation of perturbed cell states. Beyond generation, FORM can predict downstream signalling activity, simulate combinatorial perturbation effects, and model morphodynamic transitions between states of unseen perturbations. To evaluate performance, we introduce MorphoEval, a benchmarking suite that quantifies perturbation-induced morphological changes in structural, statistical, and biological dimensions. Together, FORM and MorphoEval work toward the realisation of the 3D virtual cell by linking morphology, perturbation, and function through high-resolution predictive simulation.

三维建模细胞形态扩散模型虚拟细胞

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