The RDA Working Group Building Immune Digital Twins (BIDT) developed a set of open, FAIR-aligned resources and community recommendations to accelerate the creation, reuse, and adoption of Immune Digital Twins (IDTs) and broader Medical Digital Twins (MDTs). Over its lifecycle, the WG combined multidisciplinary expertise (immunology, systems biology, clinical research, standards/ontology, software, ethics and policy) to address key barriers: fragmented knowledge, limited model discoverability and interoperability, inconsistent curation practices, and unclear guidance for responsible deployment.

The WG produced three main outputs. First, an open literature repository (Zotero) containing 112 curated publications on immune/medical digital twins with structured metadata to support systematic discovery and evidence tracking. Second, ImmunoGit, an openly accessible model repository and metadata catalogue hosted on GitHub/GitHub Pages, including 152 computational models of the human immune system (131 SBML and 21 SBML-Qual) organised by source and biological theme, with standardised metadata and API-based integration pathways (e.g., BioModels). Third, a best-practice recommendation document structured into six chapters covering the immune system context, standards and ontologies, literature curation, multiscale modelling approaches, model curation guidelines, and policy/ethics/regulatory considerations.

Together, these outputs provide a practical foundation for building, curating, sharing, simulating, and sustaining immune digital twins—supporting researchers, clinicians, infrastructure providers, and other stakeholders seeking interoperable and trustworthy IDT/MDT pipelines.

Digital Twins is a crucial technology for personalised medicine at different “levels”: generic, population-specific, and subject-specific. To build a Medical Digital Twin (MDT), one needs to cross scales, propose hybrid methods, overcome computational costs, access data, integrate them, and build a system capable of receiving feedback and recalibrating. An MDT must combine computational models to simulate multiple biological processes simultaneously. Appropriate methodological advancements are needed for efficient model analysis, integration, and calibration. Moreover, guidelines and best practices for building, hosting, adapting, simulating, and maintaining the Digital Twins are of utmost importance. The RDA BIDT WG focused on these issues and sought to address them by leveraging its members’ multidisciplinary, complementary expertise. 

The outcomes of the WG Building Immune Digital Twins hold immense value for diverse stakeholders, including researchers, clinicians, practitioners, patients, and entities across the medical and healthcare landscape. Intended adopters of the WG’s outcomes include researchers and practitioners engaged in immune system research, as well as professionals in epidemiology and healthcare technology. 

Clinicians working on or searching for advanced tools for personalised medicine will find significant utility in this WG’s deliverables. The beneficiaries extend to the broader healthcare ecosystem, including patient associations, NGOs, and companies invested in advancing healthcare technologies. The WG’s inclusive approach and our stakeholder network ensured that adopters and beneficiaries were actively involved throughout the process. Researchers and clinicians are integral members, contributing expertise to the development of catalogues, repositories, and best-practice guidelines.

Contribution of the BIDT RDA Working Group to the United Nations’ Sustainable Development Goals (SDGs)  https://sdgs.un.org/goals

Goal 3: Good Health and Well-being: The project directly contributes to enhancing health outcomes by creating advanced medical digital twins that model the immune system. This technology can transform personalised medicine by enabling optimised treatment and advancing disease diagnosis. The effort to improve understanding of the immune system and its role in diverse medical conditions consistently supports good health and well-being. 

Goal 5: Achieve gender equality and empower all women and girls: Our community is dedicated to achieving Goal 5 (Gender Equality) by promoting inclusivity and diversity. The project ensures gender balance in representation, particularly in leadership roles, fostering an environment where women scientists actively inspire other scientists. Moreover, the deliberate selection of prominent women as WG chairs and workshop speakers challenges stereotypes, inspires women to pursue STEM careers, and helps dismantle biases in the field. By actively working towards gender equality, the project aligns with Goal 5. It plays a crucial role in empowering women across many fields of expertise in the project. 

Goal 10: Reduce inequality within and among countries: Our WG recognises the complexity of the immune system and the challenges associated with many aspects of a patient’s immune state, diagnosis, and treatments (when available). By implementing collaborative, interdisciplinary initiatives, the project could help mitigate healthcare disparities. The rise and availability of advanced medical digital twins may have extensive positive effects on individuals worldwide, reducing the costs of diagnosis and therapy by providing personalised, more precise care in an open-science-aligned philosophy, accessible to everyone, aiding in the mitigation of health inequalities both domestically and internationally.

Goal 17: Partnerships for the goals: Establishing the WG Building Immune Digital Twins underscores the importance of partnerships and collaboration. By bringing together experts from various fields, the project aims to create a network of collaborators in immune system research and digital twins, as well as diverse stakeholders, aiming to accelerate and implement the adoption of the developed DTs. This collaborative effort promotes knowledge sharing, resource pooling, and a collective approach to address the challenges of developing immune digital twins. Such partnerships are crucial for achieving sustainable development goals by leveraging diverse expertise and resources.

Niarakis, A., Laubenbacher, R., An, G., Geris, L., Reiche, K., Glazier, J., Kumar Jolly, M., Hiroi, N. F., & Building Immune Digital Twins WG. (2026). Building Immune Digital Twins WG Final Recommendations. Research Data Alliance. https://doi.org/10.15497/RDA00156

1. Niarakis, A., Laubenbacher, R., An, G. et al. Immune digital twins for complex human pathologies: applications, limitations, and challenges. npj Syst Biol Appl 10, 141 (2024). https://doi.org/10.1038/s41540-024-00450-5
2. Anna Niarakis, Gary An, Luiz Ladeira, Noriko F. Hiroi, Athina Papadopoulou, Francis P. Crawley, Niloofar Nikaein, Laurence Calzone, Eirini Tsirvouli, Hasan Balci, Marina Esteban Medina, Lorenzo Veschini, Ozan Ozisik, Francesco Messina, Malvina Marku, Van Du T. Tran, Arnau Montagud, Nikola Schlosserova, Yashwanth Subbannayya, Martina Kutmon, Michael L. Blinov, Rahuman S Malik Sheriff, Robert Phair, Peter Hunter, Kristin Reiche, Jasmin Fisher, Liesbet Geris, Yaron Ilan, James A. Glazier, Philippe Moingeon, Reinhard Laubenbacher, Building immune digital twins: An international and transdisciplinary community effort, ImmunoInformatics, Volume 20, 2025, 100060, ISSN 2667-1190, https://doi.org/10.1016/j.immuno.2025.100060