Lingshu-Cell: A generative cellular world model for transcriptome modeling toward virtual cells

• URL: http://arxiv.org/abs/2603.25240v1
• Date: Thu, 26 Mar 2026 09:46:27 GMT
• Title: Lingshu-Cell: A generative cellular world model for transcriptome modeling toward virtual cells
• Abstract summary: Lingshu-Cell is a discrete diffusion model that learns transcriptomic state distributions and supports conditional simulation under perturbations.<n>It captures complex transcriptome-wide expression dependencies across approximately 18,000 genes without relying on prior gene selection.<n>It achieves leading performance on the Virtual Cell Challenge H1 genetic perturbation benchmark and in predicting cytokine-induced responses in human PBMCs.
• Score: 48.885716676667776
• License: http://arxiv.org/licenses/nonexclusive-distrib/1.0/
• Abstract: Modeling cellular states and predicting their responses to perturbations are central challenges in computational biology and the development of virtual cells. Existing foundation models for single-cell transcriptomics provide powerful static representations, but they do not explicitly model the distribution of cellular states for generative simulation. Here, we introduce Lingshu-Cell, a masked discrete diffusion model that learns transcriptomic state distributions and supports conditional simulation under perturbation. By operating directly in a discrete token space that is compatible with the sparse, non-sequential nature of single-cell transcriptomic data, Lingshu-Cell captures complex transcriptome-wide expression dependencies across approximately 18,000 genes without relying on prior gene selection, such as filtering by high variability or ranking by expression level. Across diverse tissues and species, Lingshu-Cell accurately reproduces transcriptomic distributions, marker-gene expression patterns and cell-subtype proportions, demonstrating its ability to capture complex cellular heterogeneity. Moreover, by jointly embedding cell type or donor identity with perturbation, Lingshu-Cell can predict whole-transcriptome expression changes for novel combinations of identity and perturbation. It achieves leading performance on the Virtual Cell Challenge H1 genetic perturbation benchmark and in predicting cytokine-induced responses in human PBMCs. Together, these results establish Lingshu-Cell as a flexible cellular world model for in silico simulation of cell states and perturbation responses, laying the foundation for a new paradigm in biological discovery and perturbation screening.

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