Virtual Physiological Human

The Virtual Physiological Human (VPH) is a methodological and technological framework that, once established, will enable collaborative investigation of the human body as a single complex system.^[1][2] The collective framework will make it possible to share resources and observations formed by institutions and organizations creating disparate, but integrated computer models of the mechanical, physical and biochemical functions of a living human body.

The Virtual Physiological Human (VPH) is a framework which aims to be descriptive, integrative and predictive:^[3][4][5][6]

• Descriptive. The framework should allow observations made in laboratories, hospitals and the field, at a variety of locations situated anywhere in the world, to be collected, catalogued, organized, shared and combined in any possible way.

• Integrative. The framework should enable experts to analyse these observations collaboratively and develop systemic hypotheses that involve the knowledge of multiple scientific disciplines.

• Predictive. The framework should make it possible to interconnect predictive models defined at different scales, with multiple methods and varying levels of detail, into systemic networks that solidify those systemic hypotheses; it should also make it possible to verify their validity by comparison with other clinical or laboratory observations.

The framework is formed by large collections of anatomical, physiological, and pathological data stored in digital format, by predictive simulations developed from these collections, and by services intended to support researchers in the creation and maintenance of these models, as well as in the creation of end-user technologies to be used in the clinical practice. Virtual Physiological Human (VPH) models aim to integrate physiological processes across different length and time scales (multi-scale modelling).^[3] These models make possible the combination of patient-specific data with population-based representations. The objective is to develop a systemic approach which avoids a reductionist approach and seeks not to subdivide biological systems in any particular way by dimensional scale (body, organ, tissue, cells, molecules), by scientific discipline (biology, physiology, biophysics, biochemistry, molecular biology, bioengineering) or anatomical sub-system (cardiovascular, musculoskeletal, gastrointestinal, etc.).^[5]

History of Virtual Physiological Human (VPH)

The initial concepts that brought to the Virtual Physiological Human came from the IUPS physiome project. The IUPS physiome project was formed in 1997, and was the first worldwide effort to define the physiome through the development of databases and models which facilitated the understanding of the integrative function of cells, organs, and organisms.^[7] The project focused on compiling and providing a central repository of databases, linking experimental information and computational models from many laboratories into a single, self-consistent framework.

The Physiome is the quantitative and integrated description of the functional behaviour of the physiological state of an individual or species.^[8]

Following the launch of the Physiome Project, there were many other worldwide initiatives of loosely coupled actions all focusing on the development of methods for modelling and simulation of human pathophysiology. In 2005, an expert workshop of the Physiome was held as part of the Functional Imaging and Modelling of the Heart Conference in Barcelona where a White Paper^[9] was created. The paper was entitled ‘Towards Virtual Physiological Human: Multilevel modelling and simulation of the human anatomy and physiology’. The goal of this paper was to shape a clear overview of on-going relevant VPH activities, to build a consensus on how they can be complemented by new initiatives for researchers in the EU and to identify possible mid-term and long term research challenges.

In 2006 the European Commission funded a coordination and support action entitled STEP: Structuring The EuroPhysiome. The STEP consortium promoted a very large consensus process that involved more than 300 stakeholders including researchers, industry experts, policy makers, clinicians, etc. The prime result of this process was a booklet entitled Seeding the EuroPhysiome: A Roadmap to the Virtual Physiological Human.^[6] The STEP action and the resulting research roadmap were instrumental in the development of the concept of Virtual Physiological Human here provided, and in the initiation of much larger process that involves significant research funding, large collaborative projects, and a number of connected initiatives, not only in Europe but also in the United States, Japan, and China.

The Virtual Physiological Human now forms a core target of the 7th Framework Programme ^[10] of the European Commission, and aims to support the development of patient-specific computer models and their application in personalised and predictive healthcare.^[11] The Virtual Physiological Human Network of Excellence VPH NoE aims to connect the various VPH projects within the 7th Framework Programme.

Aim of the Virtual Physiological Human

VPH related projects have received substantial funding from the European Commission in order to further scientific progress in this area. The European Commission is insistent that VPH-related projects demonstrate strong industrial participation and clearly indicate a route from basic science into clinical practice.^[5] In the future, it is hoped that the VPH will eventually lead to a better healthcare system which aims to have the following benefits:^[6]

• personalized care solutions
• reduced need for experiments on animals
• more holistic approach to medicine
• preventative approach to treatment of disease

Personalized care solutions are a key aim of the VPH, with new modelling environments for predictive, individualized healthcare to result in better patient safety and drug efficacy. It is anticipated that the VPH could also result in healthcare improvement through greater understanding of pathophysiological processes.^[3] The use of biomedical data from a patient to simulate potential treatments and outcomes could prevent the patient from experiencing unnecessary or ineffective treatments.^[12] The use of in silico (by computer simulation) modelling and testing of drugs could also reduce the need for experiments on animals.

A future goal is that there will be also be a more holistic approach to medicine with the body treated as a single multi organ system rather than as a collection of individual organs. Advanced integrative tools should further help to improve the European healthcare system on a number of different levels that include diagnosis, treatment and care of patients and in particular quality of life.^[6]

The Virtual Physiological Human is in conclusion a framework of methods and technologies that once fully established will make possible Personalised, Predictive, and Integrative medicine.

See also

• Physiome
• Physiology
• EuroPhysiome
• Cytome
• Human anatomy
• Living Human Project
• VPHOP (Osteoporotic Virtual Physiological Human)
• EuResist (Integrated system for the clinical management of antiretroviral drug resistance)
• Virtual Physiological Rat
• In silico clinical trials

References

Bibliography

• Clapworthy, G., Kohl, P., Gregerson, H., Thomas, S., Viceconti, M., Hose, D., Pinney, D., Fenner, J., McCormack, K., Lawford, P., Van Sint Jan, S., Waters, S., & Coveney, P. 2007, "Digital Human Modelling: A Global Vision and a European Perspective," In Digital Human Modelling: A Global Vision and a European Perspective, Berlin: Springer, pp. 549–558.

• Hunter, P.J. 2006. Modeling living systems: the IUPS/EMBS Physiome project. Proceedings IEEE, 94, 678-991
• Viceconti, M., Testi, D., Taddei, F., Martelli, S., Clapworthy, G. J., Van Sint Jan, S., 2006. Biomechanics Modeling of the Musculoskeletal Apparatus: Status and Key Issues. Proceedings of the IEEE 94(4), 725-739.

Links to External Resources

• EuroPhysiome The Europhysiome initiative was coordinated by the STEP Coordination action, which aimed to establish a better coordination between European Physiome projects. STEP is now completed; its primary results were the establishment of the Virtual Physiological Human (VPH) concept, and the production of a European research roadmap to the realisation of the VPH.
• STEP Roadmap STEP Consortium. Seeding the EuroPhysiome: A Roadmap to the Virtual Physiological Human. [Online] 5 July 2007,
• IUPS Physiome Project The Physiome Project is a worldwide public domain effort to provide a computational framework for understanding human and other eukaryotic physiology. It aims to develop integrative models at all levels of biological organisation, from genes to the whole organism via gene regulatory networks, protein pathways, integrative cell function, and tissue and whole organ structure/function relations. University of Auckland, Auckland, New Zealand.
• VPH NoE The VPH NoE was launched in 2008 and aims to provide the necessary infrastructure including computational methodologies, tools and databases that will enable academic, clinical and industrial researchers to communicate, and to exchange data and technologies in a standardised way. The website has the latest news, events and progress of the VPH NoE, contains further information on the VPH I projects and is a useful resource to find out more about the VPH.
• BioMed Town is an online resource, borne out of the Sixth Framework Programme Coordination Action STEP (A Strategy for the Europhysiome). It is a meeting place open to Biomedical Research & Technology, Biomedical Industry and Clinical Practice, and aims to support networking and information sharing - key activities underpinning any integrative/interdisciplinary research community. It is open to all those who have a professional or educational interest in biomedical research & technology.
• Operating on the Virtual Human BBC news feature on Heart Surgery as part of the VPH Initiative (January 2009)
• PhysiomeSpace is new service currently running in beta, which makes possible the creation of heterogeneous collection of biomedical data including medical imaging, biomedical instrumentation recordings, geometries, scalar, vector and tensor fields, results from finite element, multibody dynamics, and computer fluid dynamics simulations, etc., and to share these collections, properly annotated through a powerful ontology with any other researcher you like.
• HOM Physiology is an integrated teaching simulator that operates at a gross systems level. It explores how interactions between systems lead to complex dynamical physiological effects.

External Links to VPH projects

EU FP7 VPH related Projects

Several projects have been funded within various VPH FP7-ICT EU calls:

ICT-2009.5.3.

• AIRPROM Airway Disease PRedicting Outcomes through Patient Specific Computational Modelling.
• FUSIMO Patient specific modelling and simulation of focused ultrasound in moving organs.
• GRANATUM A Social Collaborative Working Space Semantically Interlinking Biomedical Researchers, Knowledge And Data For The Design And Execution Of In-Silico Models And Experiments In Cancer Chemoprevention
• INBIOMEDVision Promoting and Monitoring Biomedical Informatics in Europe- aims to become a European-wide initiative intended to monitor the evolution of the Biomedical Informatics field and address its scientific challenges by means of collaborative efforts performed by a broad group of experts with complementary perspectives on the field.
• INTEGRATE Driving Excellence in Integrative Cancer Research through Innovative Biomedical Infrastructures.
• MYSPINE Functional prognosis simulation of patient-specific spinal treatment for clinical use.
• PICTURE Patient Information Combined for the Assessment of Specific Surgical Outcomes in Breast Cancer
• p-medicine From data sharing and integration via VPH models to personalised medicine. P-Medicine will create an infrastructure that will facilitate the translation from current practice to personalized medicine. The project is designed to bring VPH methods to three sets of clinical trials treating various cancers (leukaemia, breast cancer, Wilms' tumour).
• SYNERGY-COPD: Modelling and simulation environment for systems medicine (Chronic obstructive pulmonary disease -COPD- as a use case).
• TBICARE Evidence based Diagnostic and Treatment Planning Solution for Traumatic Brain Injuries.
• THROMBUS A quantitative model of thrombosis in intracranial aneurysms.
• VIGOR++ Virtual GastrOintestinal tRact.
• VPH-SHARE (IP) Virtual Physiological Human: Sharing for Healthcare - A Research Environment. VPH SHARE (IP) is developing an organisational framework for the widespread integration of VPH services.

ICT-2007.5.3.

• euHeart (IP) Personalised and integrated cardiac care: Patient-specific cardiovascular modelling and simulation for in silico disease understanding and management and for medical device evaluation and optimisation. (Project dates: 06/08 - 05/12).
• VPHOP (IP) Osteoporotic Virtual Physiological Human. Body to molecule patient-specific modelling technology for the diagnosis, prognosis and treatment planning of osteoporotic fractures. (Project dates: 08/08 - 08/12).
• ARTreat (IP) Multi-level patient-specific artery and atherogenesis model for outcome prediction, decision support treatment, and virtual hand-on training. (Project dates: 09/08 - 08/11).
• Synergy-COPD (STREP) Modelling and simulation environment for systems medicine (Chronic obstructive pulmonary disease -COPD- as a use case). (Project dates: 02/11 - 01/14).
• preDiCT (STREP) Virtual research environment for in silico assessment of efficacy and safety of specific drugs (cell to ventricle-level models) and faster than-real-time simulation. (Project dates: 06/08 - 05/11).
• ContraCancrum (STREP) Clinically oriented translational cancer multilevel modelling. Composite multilevel platform for simulating malignant tumour development and tumour and normal tissue response to therapeutic modalities and treatment schedules. (Project dates: 08/08 - 07/11).
• ARCH (STREP) Patient specific image-based computational modelling for improvement of short- and long-term outcome of vascular access in patient on hemodialysis therapy. (Project dates: 06/08 - 05/11).
• PASSPORT (STREP) Patient specific simulation and preoperative realistic training for liver surgery. Patient specific liver modelling combinging anatomical, mechanical, appearance and biological preoperative modelled information. (Project dates: 06/08 - 05/11).
• p-medicine (IP) From data sharing and integration via VPH models to personalised medicine. P-Medicine will create an infrastructure that will facilitate the translation from current practice to personalized medicine. The project is designed to bring VPH methods to three sets of clinical trials treating various cancers (leukaemia, breast cancer, Wilms' tumour). (Project dates: 02/11 - 01/15).
• PredictAD (STREP) From patient data to personalised healthcare in Alzheimer's Disease. New biomarkers and clinically useful tools for early Alzheimer's disease diagnosis. (Project dates: 06/08 - 05/11).
• NeoMARK (STREP) ICT enabled prediction of cancer reoccurrence. Multiscale and multilevel modelling, aimed at advancing models and methods currently in use to predict neoplastic reoccurrences, and to apply it to the study of oral cancer. (Project dates: 06/08 - 08/10).
• VPH2 (STREP) Virtual pathological heart of the virtual physiological human. Patient-specific computational modelling and simulation of the human heart to assist the cardiologist and cardiac surgeon in defining the severity and extent of disease in patients with post-ischemic Left Ventricular Dysfunction (LVD), with or without ischemic mitral regurgitation. (Project dates: 07/08 - 06/11).
• IMPPACT (STREP) Image-based multi-scale physiological planning for ablation cancer treatment. Physiological model of the liver and simulation of result of Radiofrequency Ablation (RFA) of malignant liver tumours, accounting for patient specific physiological factors. (Project dates: 08/08 - 08/11).
• HAMAM (STREP) Highly accurate breast cancer diagnosis through integration of biological knowledge, novel imaging modalities, and modelling. (Project dates: 08/08 - 08/11).
• Action-Grid (CA) International cooperative action on grid computing and biomedical informatics between the European Union, Latin America, the Western Balkans and North Africa. (Project dates: 08/08 - 11/11).
• RADICAL (CA) Road mapping technology for enhancing security to protect medical and genetic data. In depth study to determine policy roadmap for security and privacy enhancement in Virtual Physiological Human. (Project dates: 00/00 - 00/00).
• VPH-Share (CA) Virtual Physiological Human Share. Infostructure for the VPH community especially for data and knowlededge share and development for multiscale models for new VPH workflows. (Project dates: 00/00 - 00/00).

EU FP6 VPH related Projects

• @neurIST (IP) @neurIST will develop an IT infrastructure for the management of heterogeneous data associated with the diagnosis and treatment of cerebral aneurysms. (Project dates: 02/06 - 01/10).
• ACGT (IP) Advancing Clinico-genomic trials on cancer: Open Grid services for improving medical knowledge discovery The ACGT project aims to develop a GRID platform to support and stimulate further exchanges of both clinic and genetic information, with a particular focus on breast cancer treatment. (Project dates: 02/06 - 01/10).
• Health-e-Child (IP) The Health-e-Child project aims at developing an integrated healthcare platform for European paediatrics, providing seamless integration of traditional and emerging sources of biomedical information. (Project dates: 01/06 - 12/09).
• I KNOW (STREP) I-Know is a knowledge discovery IT -based tool designed to aid early stroke diagnosis, stroke treatment, drug development and identification of risk factors as targets in disease prevention for the benefit of European industry and citizens. (Project dates: 05/06 - 04/09).
• Sealife (NoE) A Semantic Grid Browser for the Life Sciences applied to the study of Infectious Diseases. The development of a browser, which will link the existing Web to the currently emerging eScience infrastructure. (Project dates: 04/06 - 03/09).
• VIROLAB (STREP) ViroLab enables easy access to distributed resources as well as the sharing, processing, and analysis of virological, immunological, clinical and experimental data. (Project dates: 03/06 - 03/09).
• ImmunoGrid (STREP) The project will focus on establishing an infrastructure for the simulation of the immune system that integrates processes at molecular, cellular, and organ levels.It will be designed for applications that support clinical outcomes. (Project dates: 02/06 - 01/09).
• LHDL (STREP) Living Human Digital Library: interactive digital library services to access collections of complex biomedical data on the musculoskeletal apparatus. (Project dates: 02/06 - 01/09).
• Simap (STREP) Simulation modelling of the MAP kinase pathway SIMAP will develop a simulation model of the cancer related MAP-kinase pathway, integrating and analyzing data from various types of resources, which may assist in the development of better cancer treatment. (Project dates: 01/06 - 12/08)
• ASSIST (STREP) Association studies assisted by inference and semantic technologies. The main objective of ASSIST is to facilitate the research for cervical cancer through a system that will virtually unify multiple patient record repositories, physically located in different medical centres/hospitals. (Project dates: 01/06 - 12/08).
• STEP (CA) STEP was a Coordination Action that sought to coordinate European activity relating to the physiome – a description of human physiology that will span multiple levels from the whole body down through the organs to the cells and beneath in an integrated manner. (Project dates: 01/06 - 03/07).
• BIOPATTERN (NoE) Computational intelligence for Bio-pattern analysis in support of eHealthcare. The goal of BIOPATTERN is to develop a pan-European, coherent and intelligent analysis of a citizen's bio-profile. (Project dates: 01/04 - 12/07).
• MATCH (STREP) MATCH project entitle the development of an automatic diagnosis system that aims to support treatment of colon cancer diseases by discovering mutations that occurs to tumour suppressor genes (TSGs) and contributes to the development of cancerous tumours. (Project dates: 08/06 - 07/08).
• MULTI - KNOWLEDGE (STREP)The MULTI-KNOWLEDGE Project aims to integrate different biomedical information from heterogeneous sources (clinical, laboratory and metabolic) with data on gene and protein expression provided by new high throughput technologies in a system committed to cardiovascular risk profiling. (Project dates: 01/06 - 03/08).
• NEUROWEB (STREP) NEUROWEB project improved healthcare delivery achieving knowledge-based, personalised diagnosis and therapy through vertical integration of existing clinical and genetic databases. (Project dates: 08/06 - 07/08).
• e-Health ERA (CA) The overall goal of the eHealth ERA project is to contribute to greater transparency of national eHealth strategies and implementation activities as well as innovation oriented research and technology development (RTD) initiatives. (Project dates: 04/05 - 06/07).
• SemanticHEALTH (CSA) SemanticHEALTH aims to develop a European and global roadmap for deployment and research in health-ICT, focusing on semantic interoperability issues of e-Health systems and infrastructures. (Project dates: 01/06 - 12/07).
• SemanticMining (NoE) Semantic Interoperability and Data Mining in Biomedicine. The aim of this project is to establish Europe as the international scientific leader in medical and biomedical informatics. The long-term goal was to develop generic methods and tools to support the critical tasks of the field. (Project dates: 01/04 - 07/07).
• SYMBIOmatics (SSA) SYMBIOmatics is a Specific Support Action that aims to identify and exploit synergies between bioinformatics and medical informatics.The project will document the state-of-the art in biomedical informatics in Europe. (Project dates: 05/05 - 11/06).
• INFOBIOMED (NoE) INFOBIOMED aims at enforcing European Biomedical Informatics as an integrative discipline with a view on supporting individualised healthcare. (Project dates: 01/04 - 06/07).
• TACIT(STREP) Technologies Augmenting Clinical InsighT. The TACIT project aim is to unlock the tacit knowledge of Europe's senior clinicians both by linguistically analysed multimedia recording and by expert location and communications. (Project dates: 06/04 - 08/06).
• WoundMonitor (STREP) WOUNDMONITOR will apply gas sensor array technology in an innovative diagnostic system that will enable non-invasive sampling of volatiles, helping diagnosis of the onset and type of bacterial infections in critically ill patients suffering from burns or serious wounds. (Project dates: 01/06 - 12/08).
• SHARE (SSA) The goal of SHARE was to ensure the successful take up of HealthGrids in the next 10 years by creating a roadmap for essential technology development years. (Project dates: 01/06 - 03/08).
• EuResist (STREP) The EuResist project aims to develop a European integrated system for the clinical management of antiretroviral drug resistance. (Project dates: 01/06 - 06/08).
• normaCOR The aim of normaCOR is to provide novel insight into novel arrhythmogenic mechanisms, quantify their interrelation, target preventive and therapeutic interventions to reduce the societal and economical impact of cardiac arrhythmia.