CellForge: Agentic Design of Virtual Cell Models
Authors: name: Xiangru Tang; name: Zhuoyun Yu; name: Jiapeng Chen; name: Yan Cui; name: Daniel Shao; name: Weixu Wang; name: Fang Wu; name: Yuchen Zhuang; name: Wenqi Shi; name: Zhi Huang; name: Arman Cohan; name: Xihong Lin; name: Fabian Theis; name: Smita Krishnaswamy; name: Mark Gerstein
Published: 2025-08-04 10:43:31

Abstract: Virtual cell modeling represents an emerging frontier at the intersection of
artificial intelligence and biology, aiming to predict quantities such as
responses to diverse perturbations quantitatively. However, autonomously
building computational models for virtual cells is challenging due to the
complexity of biological systems, the heterogeneity of data modalities, and the
need for domain-specific expertise across multiple disciplines. Here, we
introduce CellForge, an agentic system that leverages a multi-agent framework
that transforms presented biological datasets and research objectives directly
into optimized computational models for virtual cells. More specifically, given
only raw single-cell multi-omics data and task descriptions as input, CellForge
outputs both an optimized model architecture and executable code for training
virtual cell models and inference. The framework integrates three core modules:
Task Analysis for presented dataset characterization and relevant literature
retrieval, Method Design, where specialized agents collaboratively develop
optimized modeling strategies, and Experiment Execution for automated
generation of code. The agents in the Design module are separated into experts
with differing perspectives and a central moderator, and have to
collaboratively exchange solutions until they achieve a reasonable consensus.
We demonstrate CellForge's capabilities in single-cell perturbation prediction,
using six diverse datasets that encompass gene knockouts, drug treatments, and
cytokine stimulations across multiple modalities. CellForge consistently
outperforms task-specific state-of-the-art methods. Overall, CellForge
demonstrates how iterative interaction between LLM agents with differing
perspectives provides better solutions than directly addressing a modeling
challenge. Our code is publicly available at
https://github.com/gersteinlab/CellForge.