arXiv:2605.28111cs.LG2026-05

用一步模型预测细胞在刺激或扰动下的状态变化,速度快且具可迁移性。

Chreode: A Cell World Model for One-Step Temporal Dynamics and Perturbation Prediction

  • 设计结构化残差过渡算子,实现单步细胞状态转移预测。
  • 在240万鼠胚胎细胞数据上预训练,提升多种任务性能。
  • 预训练动态表示可迁移至基因扰动预测,无需修改训练流程。

预测细胞在发育信号或遗传扰动下的转录状态变化,是虚拟细胞与计算生物学的核心。现有方法或忽略时间的静态映射,或独立求解多步常微分方程/薛定谔桥问题。我们提出Chreode,一种一步式细胞世界模型,通过结构化残差过渡算子预测动作条件下的细胞状态转移。它将分布演化从推理时间转移到训练时间,实现单次生成,同时保留基于Waddington景观的分解:下坡流、切向旋转动力学与随机扩散。模型在包含7个数据集的240万细胞小鼠胚胎图谱上,使用共享scVI编码器和基于DiT的动力学主干进行预训练。作为微调初始化,Chreode在Weinreb造血与Veres胰岛分化任务中优于基线模型(如PI-SDE、PRESCIENT),显著降低目标间Sinkhorn距离。作为GEARS的可迁移基因状态嵌入,其预训练动态表示将Norman Perturb-seq的共享词汇表DE20均方误差从0.2121降至0.1858,相对改善12.4%,且不改变原有训练过程。该迁移效果表明,预训练的发育轨迹动态编码了可迁移的分化原语,适用于CRISPR诱导的状态跃迁,二者均在共享潜在几何空间中完成细胞状态转移。此外,预训练主干在Weinreb数据上零样本生成克隆命运评分,表现媲美强动态最优传输基线。

原文摘要 · Abstract (English)

Predicting how a cell will change its transcriptional state under a developmental signal or a genetic perturbation is the computational core of in-silico biology and the AI Virtual Cell program. Existing approaches either fit static control-to-treated maps that discard time, or solve multi-step ODE / Schrödinger-bridge problems on each dataset independently. We introduce Chreode, a one-step cell world model that predicts action-conditioned cell-state transitions through a structured residual transition operator. It shifts distributional evolution from inference time to training time, enabling single-pass generation while preserving a Waddington-inspired decomposition into downhill landscape flow, rotational in-tangent dynamics, and stochastic spread. The model is pretrained with a shared scVI encoder and a DiT-based dynamics backbone on a 2.4M-cell mouse embryonic atlas spanning 7 datasets. As a fine-tuning initialization, Chreode improves per-target Sinkhorn distance on Weinreb hematopoiesis and Veres islet differentiation over matched scratch models, PI-SDE, and PRESCIENT. As a transferable gene-state embedding for GEARS, the pretrained dynamics representation reduces shared-vocabulary DE20 mean squared error on Norman Perturb-seq from 0.2121 to 0.1858, a 12.4% relative improvement, without changing the GEARS training procedure. We interpret this transfer to perturbation prediction as evidence that pretrained developmental-trajectory dynamics encode differentiation primitives transferable to CRISPR-induced state shifts, since both involve cell-state transitions in a shared latent geometry. The pretrained backbone additionally produces zero-shot clonal fate scores on Weinreb that are competitive with strong dynamic-OT baselines.

细胞建模动态预测迁移学习单步生成

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