An immune world model for multiscale forecasting and therapeutic hypothesis generation
Taoyong Cui, Xi Wang, Zonghang Li, Jinchao Ding, Lingsen You, Yuzhi Xu, Wanghan Xu, Fang Wu, Kejun Ying, Wanli Ouyang, Pheng Ann Heng, Ling Yang, Zhenfei Yin, Yingcheng Wu
Abstract
Immune therapies act across cell-intrinsic programs, tissue ecosystems, and patient-specific immune states, yet most predictors address these scales separately. We used a governed evolutionary AI Scientist to construct the Immune World Model, an action-conditioned model that learns how interventions move immune states across cellular, tissue, and individual levels. The Immune World Model--building Scientist searched candidate architectures and workflows, and the resulting world model was frozen before independent confirmation. The frozen model generalized to unseen interventions and biological contexts, recovered intervention-specific cellular programs, integrated cell and tissue information to improve ecosystem and patient-response prediction, and forecast unseen perturbation combinations. Immune World Model--guided analysis then combined measured perturbations with cross-axis inference to nominate IL-36$γ$ plus SIRP$α$ inhibition as a complementary-axis therapeutic hypothesis, whereas a governed self-correction audit rejected every screened cytokine pair. The Immune World Model provides a framework for multiscale immune simulation that connects AI Scientist-driven model construction, intervention forecasting, and the generation of prospectively testable therapeutic hypotheses.