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

arXiv: https://arxiv.org/abs/2605.28111 · HTML: https://mlsanity.com/paper/2605.28111/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Medical and surgical world models, one of 11 directions in World models.
- Builds on 11 of its 31 references that are in the map.
- First posted on arXiv 27 May 2026.

## Placed in

- World models / [Medical and surgical world models](https://mlsanity.com/wm/medical-and-surgical-world-models/)

## Builds on (most cited first, 11 of 11)

- [Scalable Diffusion Models with Transformers](https://mlsanity.com/paper/2212.09748/) (2022)
- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Dream to Control: Learning Behaviors by Latent Imagination](https://mlsanity.com/paper/1912.01603/) (2019)
- [World Models](https://mlsanity.com/paper/1803.10122/) (2018)
- [Improving and generalizing flow-based generative models with minibatch optimal transport](https://mlsanity.com/paper/2302.00482/) (2023)
- [Time2Vec: Learning a Vector Representation of Time](https://mlsanity.com/paper/1907.05321/) (2019)
- [TrajectoryNet: A Dynamic Optimal Transport Network for Modeling Cellular Dynamics](https://mlsanity.com/paper/2002.04461/) (2020)
- [Generative Modeling via Drifting](https://mlsanity.com/paper/2602.04770/) (2026)
- [How to Build the Virtual Cell with Artificial Intelligence: Priorities and Opportunities](https://mlsanity.com/paper/2409.11654/) (2024)
- [Branched Schr"odinger Bridge Matching](https://mlsanity.com/paper/2506.09007/) (2025)
- [CellStream: Dynamical Optimal Transport Informed Embeddings for Reconstructing Cellular Trajectories from Snapshots Data](https://mlsanity.com/paper/2511.13786/) (2025)

## Abstract (arXiv)

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 / Schr"odinger-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.