VCWorld: A Biological World Model for Virtual Cell Simulation

Fuente: arXiv
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Autori principali: Wei, Zhijian, Ma, Runze, Wang, Zichen, Li, Zhongmin, Song, Shuotong, Zheng, Shuangjia
Natura: Preprint
Pubblicazione: 2025
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author Wei, Zhijian
Ma, Runze
Wang, Zichen
Li, Zhongmin
Song, Shuotong
Zheng, Shuangjia
author_facet Wei, Zhijian
Ma, Runze
Wang, Zichen
Li, Zhongmin
Song, Shuotong
Zheng, Shuangjia
contents 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 benchmarks, VCWorld achieves state-of-the-art predictive performance, and the inferred mechanistic pathways are consistent with publicly available biological evidence.
format Preprint
id arxiv_https___arxiv_org_abs_2512_00306
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle VCWorld: A Biological World Model for Virtual Cell Simulation
Wei, Zhijian
Ma, Runze
Wang, Zichen
Li, Zhongmin
Song, Shuotong
Zheng, Shuangjia
Cell Behavior
Artificial Intelligence
Machine Learning
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 benchmarks, VCWorld achieves state-of-the-art predictive performance, and the inferred mechanistic pathways are consistent with publicly available biological evidence.
title VCWorld: A Biological World Model for Virtual Cell Simulation
topic Cell Behavior
Artificial Intelligence
Machine Learning
url https://arxiv.org/abs/2512.00306