[2512.00306] VCWorld: A Biological World Model for Virtual Cell Simulation

Quantitative Biology > Cell Behavior arXiv:2512.00306 (q-bio) [Submitted on 29 Nov 2025 (v1), last revised 27 Feb 2026 (this version, v2)] Title:VCWorld: A Biological World Model for Virtual Cell Simulation Authors:Zhijian Wei, Runze Ma, Zichen Wang, Zhongmin Li, Shuotong Song, Shuangjia Zheng View a PDF of the paper titled VCWorld: A Biological World Model for Virtual Cell Simulation, by Zhijian Wei and 5 other authors View PDF Abstract:Virtual cell modeling aims to predict cellular responses to perturbations. Existing virtual cell models rely heavily on large-scale single-cell datasets, learning explicit mappings between gene expression and perturbations. Although recent models attempt to incorporate multi-source biological information, their generalization remains constrained by data quality, coverage, and batch effects. More critically, these models often function as black boxes, offering predictions without interpretability or consistency with biological principles, which undermines their credibility in scientific research. To address these challenges, we present VCWorld, a cell-level white-box simulator that integrates structured biological knowledge with the iterative reasoning capabilities of large language models to instantiate a biological world model. VCWorld operates in a data-efficient manner to reproduce perturbation-induced signaling cascades and generates interpretable, stepwise predictions alongside explicit mechanistic hypotheses. In drug perturbation ben...