Organizations: PhAI Labs, Inc., Palo Alto, CA, USA · Department of Computer Science and Engineering, The Chinese University of Hong Kong, Hong Kong SAR, China · Multimedia Laboratory, Department of Information Engineering, The Chinese University of Hong Kong, Hong Kong SAR, China · Department of Chemistry, New York University, New York, NY, USA · Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA · Shanghai Jiao Tong University, Shanghai, China · Department of Computer Science, Stanford University, Stanford, CA, USA · Harvard University, Cambridge, MA, USA · Princeton University, Princeton, NJ, USA · University of Oxford, Oxford, UK
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-36γ plus SIRPα 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.
State Key Laboratory of Networking and Switching Technology, Beijing University of Posts and Telecommunications, Beijing, China · Department of Engineering Science, University of Oxford, Oxford, United Kingdom · Institute of Medical Artificial Intelligence, South China Hospital, Medical School, Shenzhen University, Shenzhen, Guangdong, China +8
College of Computer Science, Zhejiang University, Hangzhou, China. · School of Medicine, Zhejiang University, China. · Department of Biomedical Informatics, Harvard University, USA.