Organizations: School of Biomedical Engineering, Southern Medical University, Guangzhou, China. · Guangdong Provincial Key Laboratory of Medical Image Processing, Southern Medical University, Guangzhou, China. · Guangdong Province Engineering Laboratory for Medical Imaging and Diagnostic Technology, Southern Medical University, Guangzhou, China. · MOE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China.
Abstract
Modeling tissue states and their transitions is essential for understanding tissue homeostasis in health and pathological remodeling in disease. However, conventional computational modeling approaches are inadequate to capture the complexity of tissues as spatially organized, multiscale biological systems. Artificial intelligence (AI) has shown a remarkable ability for representing intricate systems, creating new opportunities to characterize tissue states and their transitions. Here, we propose the concept of AI virtual tissue (AIVT), an AI framework grounded in spatial multimodal data for modeling tissues in health and disease. AIVT is designed to learn unified, spatially resolved, and dynamically manipulatable representations of tissue state, enabling tissue state representation and analysis, molecular and morphological feature prediction, and simulation of spatiotemporal tissue dynamics. We outline the fundamental assumptions, core capabilities, architectural components, as well as data and algorithm foundations of AIVT as a framework for AI-driven tissue modeling.
Understanding tissue organisation in multiplexed imaging requires modelling both cellular phenotypes and their spatial context. Existing approaches typically rely on handcrafted features, such as marker intensity statistics or cell-type proportions, which often fail to scale or generalise across cohorts with heterogeneous marker panels. We introduce MUL-T, a lightweight transformer framework that reframes tissue architecture as a masked contextual prediction task over discrete cell tokens. By learning contextualised [CLS] embeddings without task-specific supervision, the model captures higher-order cellular interactions while remaining computationally efficient. We evaluate MUL-T on several clinically relevant downstream tasks, including core-level tumour pattern classification, patient-level grading, PD-L1 positivity prediction, and cross-dataset treatment response prediction. Across tasks, MUL-T consistently outperforms classical feature-based baselines and achieves performance comparable to a foundation ViT model, despite substantially fewer parameters and lower training cost.
Farzaneh Seyedshahi, Kai Rakovic, Adalberto Claudio Quiros +2
A central goal of biomedicine is to understand, predict and ultimately control the dynamic mechanisms by which biological systems respond to perturbations, disease progression and therapeutic intervention. Although foundation models and large language models have accelerated biomedical data interpretation, most current systems remain focused on static pattern recognition rather than prospective simulation of biological futures. Here we propose biomedical world models as a paradigm for AI-driven discovery. These models learn latent representations of molecular, cellular, tissue and clinical states, together with intervention-conditioned dynamics that allow future trajectories to be simulated before actions are taken. We discuss how biomedical world models could function as data engines, environment simulators and scientific planning substrates across applications including virtual cells, organoids, virtual patients and surgical simulation. We outline the data infrastructure, evaluation benchmarks, safety constraints and governance frameworks required. Biomedical world models may provide a foundation for simulation-guided, closed-loop and experimentally actionable biomedical discovery.
Virtual cell modeling predicts molecular state changes under genetic perturbations in silico, which is essential for biological mechanism studies. However, existing approaches suffer from unconstrained reasoning, uninterpretable predictions, and retrieval signals that are weakly aligned with regulatory topology. To address these limitations, we propose AROMA, an Augmented Reasoning Over a Multimodal Architecture for virtual cell genetic perturbation modeling. AROMA integrates textual evidence, graph-topology information, and protein sequence features to model perturbation-target dependencies, and is trained with a two-stage optimization strategy to yield predictions that are both accurate and interpretable. We also construct two knowledge graphs and a perturbation reasoning dataset, PerturbReason, containing more than 498k samples, as reusable resources for the virtual cell domain. Experiments show that AROMA outperforms existing methods across multiple cell lines, and remains robust under zero-shot evaluation on an unseen cell line, as well as in knowledge-sparse, long-tail scenarios. Overall, AROMA demonstrates that combining knowledge-driven multimodal modeling with evidence retrieval provides a promising pathway toward more reliable and interpretable virtual cell perturbation prediction. Model weights are available at https://huggingface.co/blazerye/AROMA. Code is available at https://github.com/blazerye/AROMA.