Physiological Digital Twins in Medicine: Formal Representation, Interoperability, and Validation

Digital twins are increasingly proposed as computational tools to represent organ function, patient state, and response to intervention. Their broader use in physiology and medicine depends not only on model sophistication but also on how physiological knowledge, data, and workflows are formally represented, exchanged, and validated. Without formal representation, digital twins are difficult to reuse, personalize, compare across studies, and integrate across platforms. Without rigorous validation, they remain difficult to trust for translational or clinical use.This Research Topic brings together work spanning the lifecycle of physiological digital twins, from formal model representation and interoperable implementation to verification, validation, and medically meaningful application.We welcome Original Research, Methods, Reviews, and Perspectives on:1. Formal model representation of physiological systems, including semantic annotation, metadata, ontologies, standards, and markup-based approaches2. Interoperability of models, data, and workflows across platforms, repositories, and scales3. Integration of multimodal data for digital twin development, including imaging, biosignals, experimental measurements, device data, and health records4. Mechanistic, multiscale, and hybrid digital twins, including virtual patients and virtual cohorts5. Personalization, calibration, verification, and validation, including uncertainty quantification and credibility assessment6. Applications in disease modelling, treatment planning, device evaluation, and decision supportPublisher's note:Steve McKeever (Uppsala University) is an Independent Evaluator for the European Commission, Deputy Director of the Uppsala Diabetes Centre, and is currently building a digital twin of Stockholm Airport. He has mentored researchers across the euHeart, TUMOR, and DRIVE-AB programmes, and examined doctoral theses at the Auckland Bioengineering Institute on physiological modelling languages and model repositories. Jae Ho (Mike) Lee (Old Dominion University) spent four years at FDA/CDER leading CFD modelling of orally inhaled drug products, co-authoring draft regulatory guidance, and running in silico immunogenicity evaluations under formal credibility frameworks. He trained in cardiovascular fluid-structure interaction at UNC Chapel Hill and Johns Hopkins.Manuscripts submitted to Biomechanics (Frontiers in Bioengineering and Biotechnology) would focus on validated computational biomechanics, including patient-specific models, fluid-structure interaction, finite element modelling, device evaluation, or verification and validation frameworks. Work centred mainly on interoperability, repositories, metadata standards, or unvalidated computational models would remain outside the Biomechanics scope. Topic editors: Jae Ho Lee, Steve McKeever Source: https://www.frontiersin.org/research-topics/81252/physiological-digital-twins-in-medicine-formal-representation-interoperability-and-validation