STEP : A Strategy for the EuroPhysiome Coordination Action # 017642

1. STEP: A Strategy for the EuroPhysiomeCoordination Action # 017642 Marco Viceconti Scientific Coordinator

2. Contents • consortium • context to STEP • STEP objectives and programme • STEP conferences and related activities • expected outcomes • summary

3. The Consortium • LUT - University of Luton (UK) • Project Coordinator, Gordon Clapworthy • IOR - Istituti Ortopedici Rizzoli (I) • Scientific Coordinator, Marco Viceconti • ULB - Université Libre de Bruxelles (B) • SHE - University of Sheffield (UK) • AAS - Aalborg and Aarhus University Hospitals (DK) • OXF - University of Oxford (UK) • NOT - University of Nottingham (UK) • CNRS – CNRS/LaMI (F) • UCL - University College London (UK)

4. Definition of the Physiome • The physiome is the quantitative and integrated description of the functional behavior of the physiological state of an individual or species. • The physiome describes the physiological dynamics of the normal intact organism and is built upon information and structure (genome, proteome, and morphome). The term comes from "physio-" (life) and "-ome" (as a whole). In its broadest terms, it should define relationships from genome to organism and from functional behavior to gene regulation. In context of the Physiome Project, it includes integrated models of components of organisms, such as particular organs or cell systems, biochemical, or endocrine systems.

5. The Physiome Project • The Physiome Project is a worldwide effort to define the physiome through the development of databases and models which will facilitate the understanding of the integrative function of cells, organs, and organisms. • The Physiome Project is a grass-root all-inclusive initiative, not linked to a particular country, research institution, or research community, that welcome anyone willing to contribute to the development of the Physiome. • The project has the following scopes: • to promote the concept of Physiome and its scientific, industrial, clinical and societal relevance • to identify the research challenges to be met in order to advance the general objective • to promote the synergy between Physiome-related initiatives by developing and promoting standards that ensure the creation of a fully interoperable federation of physiome repositories.

6. The Physiome Project • aims to provide a computational framework: • to facilitate the understanding of • human physiology • the integrative function of cells, organs and organisms • multiscale in silico model of human physiology • it is an international effort: • loosely coupled actions of individual labs • “grass roots” approach • noticeably gaining momentum

7. The EuroPhysiome initiative • All Physiome-related projects managed by European researchers have been recently coordinated under the STEP Coordination action • STEP: a Strategy for The EuroPhysiome aims to coordinate European efforts toward the development of the Virtual Physiological Human • This effort will materialise into a VPH roadmap document, written through a running consensus process that will involve all European stakeholders

8. Virtual Physiological Human • The term Virtual Physiological Human (VPH) indicates a shared resource formed by a federation of disparate but integrated computer models of the mechanical, physical, and biochemical functions of living human body in both physiological and pathological conditions. • This goal is coherent with those set by the international Physiome Project. • VPH models are both descriptive and predictive: • large collections of anatomical, physiological, and pathological data stored in digital format, • predictive simulations developed from these collections • services aimed to support the researchers in the creation and maintenance of these models • services aimed to empower clinical, industrial and societal users in the use of the VPH resource

9. VPH models • span multiple dimensional scales (from the whole body down to the cells and the proteins they synthesise) • account for the inter-subject variability • make possible the combination of patient-specific data with population-based representations • are implemented as computer models and services, designed following community standards that make possible to exchange information and to realise a developmental process based on the federation of the various partial representations, each already useful by itself, into what should become one day an exhaustive and complete representation of functions of the human body • To create the VPH we need brand new technologies, specifically developed to pursue this scope; this is called VPH Technology.

10. VPH Technology • VPH Technology is an organised collection of computational frameworks and ICT-based tools for the multilevel modelling and simulation of the human anatomy, physiology and pathology. • Once sufficiently developed the VPH will provide an essential technological infrastructure to the Physiome Project, to pathology-specific initiatives in translational research, and to vertical solutions for the biomedical industry.

11. The EuroPhysiome • European effort currently at “grass roots” level • “EuroPhysiome” was coined to reflect a more integrated approach to the Physiome concept from Europe • NOT isolationist • maintain the ideals / principles of the Physiome project • continue to work with labs outside Europe • BUT increase coherence within Europe • avoid redundancy/overlap • seek to develop common European approaches/ standards/ software tools/ database structures …. • increase momentum in European Physiome work to make Europe the world leader • consistent with world-wide efforts wherever possible

12. Europhysiome Projects • Cardiome • heart structure & function, based at Oxford • Epitheliome • epithelial tissue, based at Sheffield • Giome • gastroenterology, based in Aalborg • Living Human • musculo-skeletal, based at IOR • ULB virtual human • musculo-skeletal, based at ULB • Renal Physiome • kidney, based at CNRS-LaMI in Evry • Physiological Flow Network • physiological flows, based at Nottingham

13. STEP Objectives • To bring together all current Physiome-related activity in Europe • To create a roadmap that will ensure that future European work will be coherent, integrated and internationally competitive • this implies that European projects: • develops a broader perspective • moves from a project-based outlook to a Physiome-based outlook • To provide the opportunity for all relevant work in Europe to participate in the above process

14. Boundaries • attempting to consider the whole body is too ambitious for a simple CA • exclude brain and perceptual/cognitive aspects of the sensorial apparatus • concentrate on subsystems for which physics-based modelling is a fundamental aspect • cardiovascular, musculoskeletal, respiratory, digestive, skin (within restrictions noted) • this represents a broad, but relatively homogeneous domain • European work in this area is already recognised as being strong

15. WP3 M1–M15 Discussion Groups & Mailing Lists WP1 M0–M15 Co-ordination & management WP2 M0–M4 Organisation of the First Conference WP4 M3–M12 Organisation of the Second Conference WP5 M12–M15 Production of the Road Map WP6 M0–M15 Dissemination Project structure

16. The scope of the Roadmap • Identify the Grand Challenges that we must overcome to achieve the VPH objective • Provide to the European Commission and to other grant agencies a research roadmap for the Virtual Physiological Human, to be used for strategic planning of research funding • Evangelise research, clinical and industrial stakeholders on the concepts of Physiome, VPH and VPH Technology • Inform the citizens of Europe of the potential impact that VPH research may have of their daily lives

17. The road to the Roadmap

18. The road to the Roadmap

19. Strands • we have already noted the importance of moving from a project-based outlook to a Physiome-based outlook • however: • considering the Physiome as a whole (even within the boundaries described) would be highly complex • so: • break down the large problem into a set of smaller problems, suitably defined • STEP has defined a set of Strands • suited to the restricted domain defined for the project

20. Strands (cont’d) • the strands defined cover tissue types: • hard tissue (coordinator IOR) • soft tissue (coordinator AAS) • fluids (coordinator SHE) • they also cover more general common aspects across all tissue types • anatomy & physiology (coordinator ULB) • Multiscale modelling (coordinator OXF) • VPH Technology (coordinator LUT)

21. Expert Panels & Advisory Board • for each Strand Panel a group of world-known experts will be invited to contribute to the consensus • there will also be an Advisory Board formed of senior figures who will provide a strategic view and will review all draft documents produced by the panels • all of these will have some members from outside Europe to avoid too introspective a discussion • all stakeholders should be represented: • industrial, clinical, professional bodies, societal, etc