Abstract
P4 medicine (Predictive, Preventive, Personalized, and Participatory) offers a comprehensive approach to personalized healthcare, emphasizing both the transition from disease to wellness and the importance of preventive care. In this perspective, we propose a novel extension to P4 medicine. Specifically, we argue that combining P4 medicine with digital twins (DTs) introduces capabilities that elevate it far beyond its current scope. While P4 medicine provides a conceptual framework grounded in medical principles, digital twins offer a complementary framework for methodological realization. Together, these concepts form a synergistic pairing, interfacing through individual patients and their corresponding data. Furthermore, we emphasize that digital twins represent a new paradigm-not merely a method-characterized by four critical features: explainability, intervenability, learnability, and diversability. We believe that this integration unlocks capabilities that go beyond the reach of traditional bioinformatics and systems biology approaches.