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During the 22nd Virtual Plenary, the Building Immune Digital Twins RDA WG hosted a lively session that served as a discussion forum for brainstorming and exchanging information on all the scientific aspects of building and validating immune system models for different purposes. Discussions and presentations highlighted various use cases, an Immune Digital Twin roadmap and important milestones, while also highlighting the scientific, technical and organisational challenges.

Background

Digital twins, initially developed in industry, are gaining momentum in healthcare, particularly in cardiovascular diagnostics and insulin pump control. They are also pivotal in drug development and optimising personalised treatments for patients. Advanced medical digital twins are crucial for advancing personalised medicine, placing the patient at the centre. The immune system’s pivotal role in various health conditions makes digital twins of the immune system (IDTs) especially significant. However, their development faces significant challenges due to the immune system’s complexity and limitations in measuring immune states in patients. Progress necessitates collaborative efforts among immunologists, clinicians, mathematical modellers, and software engineers.

Figure 1. Building digital twins of the human immune system. From Laubenbacher, R., Niarakis, A., et al. Building digital twins of the human immune system: toward a roadmap. npj Digit. Med. 5, 64 (2022). https://doi.org/10.1038/s41746-022-00610-z
VP22 virtual meeting

On May 21st, the WG Building Immune Digital Twins held a virtual session to introduce the group’s main objectives and challenges, present key challenges and the state of the art through short presentations by experts in relevant fields, and discuss openly the various steps that need to be taken to bring IDTs to life. The main host of the session, Dr Anna Niarakis, Professor of Computational Systems Biology & Bioinformatics, University of Toulouse III – Paul Sabatier, Centre of Integrative Biology, Laboratory Molecular, Cellular and Developmental Biology, and main chair of the WG, coordinated discussions accompanied by co-chair Dr Reinhard Laubenbacher, Professor of Systems Medicine, Department of Medicine, University of Florida, US. The session started with a brief introduction and continued with the presentations of the invited speakers, followed by short Q&As.

Invited speakers:

At the end of the session, a lively round table discussion with the participation of hosts and speakers took place, where all participants exchanged on a broad array of key points covering most aspects of building IDTs.  

Key outcomes and takeaways

The participants discussed the difficulties of IDT implementation in preclinical and clinical settings and the steps forward that need to be taken to facilitate the best possible integration of in silico tools with current diagnostic practices. Specifically, the goal is to enable early diagnosis, predict disease progression, and tailor individualized therapeutic interventions. Achieving these objectives will significantly enhance patient outcomes and optimize healthcare resources.

The building and deployment of IDTs require considerable scaling up in terms of the modelled systems and the development of robust formal methods that can tackle such complexity and reduce computational cost. New methodologies that can integrate big heterogeneous datasets, along with the development of new tools and algorithms for model building, analysis and parametrisation, will serve as cornerstones for the IDTs.  Additionally, addressing the stochastic nature of immune responses and developing real-time simulation capabilities are critical challenges. Enhancing the interpretability of complex models for clinical application also remains a significant hurdle.

The endeavour requires interdisciplinarity and complementary expertise in mathematics, informatics, biology, commuter science, immunology and engineering. Collaboration among experts in data science, machine learning, and systems biology is also essential to advance IDT development. Effective communication and coordination among these diverse disciplines will ensure a cohesive and comprehensive approach to the project.

Access to rigorous computational infrastructure and HPC, access to biomedical and clinical data, generous funding for at least five to ten years, and talented, determined scientists to pave the way, because robust data security and privacy measures are necessary to protect sensitive patient information. Establishing long-term partnerships with healthcare institutions can facilitate continuous access to critical clinical data.

Build international and interdisciplinary consortia and working groups to exchange and collaborate in service of a shared goal. Advance computational projects in alignment with unmet clinical needs, design projects considering the clinical settings and difficulties, and foster innovation and out-of-the-box thinking to bring technology closer to healthcare. Furthermore, creating standardized protocols and frameworks for IDT development can streamline processes and ensure consistency. Encouraging open data sharing and collaborative research can also expedite progress and innovation in the field.

Everyone is welcome to join the Working Group, share their expertise and contribute toward milestones and deliverables in the next 18 months! Click below to become a member.

Next steps

Watch our session recording, and sign up to participate actively in all WG activities and updates. The RDA Technical Advisory Board is currently reviewing the case statement, and the WG will soon officially start hammering out the ambitious and impactful work plan.

Useful links

Recording of the session: https://youtu.be/pTs6zNJ0hpE?si=MUuyGoUZ6jFaEjSc 

WG page: https://www.rd-alliance.org/groups/building-immune-digital-twins-wg/ 

WG meeting report and perspective:  https://zenodo.org/records/10783684 

Roadmap: https://www.nature.com/articles/s41746-022-00610-z 

The main previous meeting of the WG: https://www.institut-pascal.universite-paris-saclay.fr/en/scientific-programs/building-immune-digital-twins 

Upcoming events: Building Immune Digital Twins mini-symposium 2024 – Immune Digital Twins – A community effort to make IDTs a reality! (immunedt.github.io)