WP2 - VPH Exemplar Projects PDF | Print | E-mail

Overview

(Nov. 2009: 18-month WP2 report on the Exemplar Projects, D2.6, is available here)

Coordinator: CNRS

In keeping with the general ethos of the VPH NoE - to support interdisciplinary and integrative research - WP2 will develop Exemplar Projects (EPs) working towards integration amongst VPH researchers, in order to address specific research problems or challenges. These projects aim is to provide solid examples of horizontal and vertical model/data integration, which may only be achieved through the integration of disparate knowledge and research infrastructure. This 'infrastructure' will be provided through development of the VPH ToolKit (WP3).

Within the first year of the project, five 'seed EPs' were and in some cases are still being carried out by VPH NoE core members. These are described below, and aim to lay the ground for subsequent EPs. Requirement of these project are as follows:

• Exemplar projects must be INTEGRATIVE
• Exemplar projects must be INTERDISCIPLINARY
• Exemplar projects must MAKE USE AND/OR CONTRIBUTE TO THE VPH ToolKit, through use/development of modelling, simulation and visualisation-related tools, data or methods.

There are now a total of 11 Exemplar Projects. There are 5 Seed Exemplar Projects, 1 project selected in the first call and 3 projects selected in the second call, and two selected in the third call. These Eps are described below.

The principal challenge in development of the VPH ToolKit is establishment of the transversal, or horizontal, connections between the usual domains of investigation. The intention in selecting the EPs (both the seedEPs and future EPs), is to push development in the direction of this transversal integration. We expect this to be one of the main hurdles to success of the collaborative/integrative approach underlying the physiome concept. It must of course rely on the technical resources that will constitute the VPH ToolKit but it represents, in some sense, a change of paradigm, towards a globalization/mondialisation of biomedical research.

SEED EXEMPLAR PROJECTS

The 5 Seed Exemplar Projects, which took place in the first 18 months of the VPH NoE project and these were:

EP1: CNRS: A multi-organ Core Model of arterial pressure and body fluids homeostasis

EP2: ULB: Integrated multi-level modelling of the musculoskeletal system

EP3: KI: Fighting aneurysmal disease (FAD)

EP4: IMIM: Multi-scale simulation and prediction of the drug safety problems related with hERG

EP5: ERCIM, Digital Patient Working Group: Modelling and visualising brain function and pathophysiology

To view an initial description of the 5 seed Exemplar Projects please click on the links above or alternatively all 5 seed Exemplar Projects can be found on the Exemplar Project page.

During the course of 2009, a first call was released for further EP proposals. Seven proposals were submitted, and one was selected as a new Exemplar Project, which is coordinated by EBI.

EP6: Establishing ontology-based methods for the VPH ToolKit to improve interoperability between  data and models: the Guyton case study

It is very important to note that subsequent exemplar projects were and will continue to be awarded as part of an open call process to VPH NoE General Members.

SECOND CALL FOR EP PROPOSALS

The second call for new Exemplar Projects was launched by the VPH NoE in the Spring of 2010. The call was open to proposals based on ongoing projects in any laboratory involved in VPH-related work, the only condition being that, if the laboratory is not already part of the VPH NoE consortium, they become a General Member of the NoE. While this call was open as usual to any proposal addressing gaps in horizontal and vertical integration in physiological modeling, it was especially targeted towards proposals addressing VPH infrastructure or workflow demonstrators.

The three projects that were selected reflect this triple goal, since they address, respectively, the role of physics-based models to link genotype to phenotype, the nature of the ICT infrastructure required for the success of the VPH mission, and lastly, the development of efficient workflows for integration of clinically oriented virtual imaging platforms and the VPH ToolKit. We give a brief overview of these three projects, all of which are just getting underway.

EP7: CIGENE: Integrating genetic theory and genomic data with multiscale models in a population context

EP8: USFD: Infrastructure" or "The NoE, Infrastructure and the Challenge of Call6

EP9: VIP for VPH : Execution of medical image simulation workflows on DEISA through workflow interoperability between the Virtual Imaging Platform and the VPH toolkit

THIRD CALL FOR EP PROPOSALS

The third and last call for new Exemplar Projects (EPs), launched in the Spring of 2011 resulted in the selection of the final two EPs, for a total of eleven. The two projects that were selected do indeed address important gaps in the previous coverage of physiological organ systems and pathologies by the NoE Exemplars, namely, sexually transmitted infections and cancer-related angiogenesis. We give a brief overview of these two projects, which are both underway since September 2011.

EP10: "Environment for Sexually Transmitted Infection Modelling" Coordinator: Martin Nelson, University of Nottingham, Centre for Mathematical Medicine & Biology (Partners: Queensland University of Technology, Australia.; Norwegian University of Science & Technology,Trondheim, Norway; Chlamydia Research Group, Arkansas Children’s Hospital Research Institute, Little Rock, Arkansas,USA)

EP10 is developing an environment for mathematical/computational modeling of sexually transmitted infections (STIs). As a representative case study, the project focuses on mark-up and simulation of three existing “within-host” models of Chlamydia trachomatis infection – the most common sexually transmitted pathogen of humans, with over 90 million new adult cases occurring worldwide each year. These models deploy multiscale approaches to describe the spatial progression of C. trachomatis infection in the female genital tract, coupling a continuum description of extracellular Chlamydial particle motion to cell-scale and tissue-scale models of infection of the genital epithelium. Model simulations will be compared to experimental data for Chlamydia caviae infection in guinea pigs, a bacterial infection highly representative of C. trachomatis infection in humans. The study will demonstrate application of existing VPH toolkit software to the reproductive system, with a focus placed upon demonstrating the interoperability of tools across different spatial scales. While a focus upon C. trachomatis is proposed, the modeling approach should be extensible to other STIs, including gonorrhea and syphilis. The project will develop a computational tool for simulation of a range of STIs, coding each component of the proposed models independently to facilitate future uptake in the study of other infections. This STI modeling environment will facilitate efficient comparison of models and results, and will be deployable in identification of suitable vaccines.

EP11: "Vascular Tissue Modelling Environment (VTME)" Coordinator: Markus Owen, University of Nottingham (Partners: Oxford University; CRM, Barcelona; Charité, Berlin; Physiology, U of Arizona, Tucson; Textensor Ltd., Edinburgh; Arizona State, Tempe; Neuroscience, Physiol. & Pharmacol, UCL)

Throughout life, almost all tissues require a blood supply to deliver nutrients and remove waste products. Problems with blood vessel development can lead to severe birth defects. Later, vascular growth and remodeling play a key role in pathologies including diabetes, macular degeneration and rheumatoid arthritis. In addition, tumor growth is crucially dependent on the host blood supply, and this has made the vascular system a major target for anti-cancer therapies. These features make patient-specific computer models of vascular tissues a natural target for the VPH. Over a number of years a multiscale model for vascular tissues has been developed by the EP11 team as part of projects funded by the EU (FP5, FP6), the UK (BBSRC, EPSRC), German (BMBF) and US (NCI/NIH) research councils. The model combines (A) fluid flow in a vessel network; (B) PDEs for the transport, release and uptake of diffusible substances such as oxygen; (C) cell division and reinforced random walks of cells on a regular lattice; (D) ODEs for subcellular networks that regulate the cell cycle and growth factors such as VEGF; and (E) integration of angiogenic and vasculogenic endothelial cells into the vascular network. The model (Owen et al. 2011, Cancer Research 71(8); Perfahl et al. 2011, PLoS ONE 6(4)) is at a stage of maturity that makes it ideal for a VPH NoE Exemplar Project, in order to reinforce these developments, and to enable re-use, integration and sharing of the model and relevant data.

EP11 will implement a user-friendly Vascular Tissue Modeling Environment (VTME) within the "Cancer, Heart and Soft Tissue Environment" tool (CHASTE, http://web.comlab.ox.ac.uk/ chaste/), already part of the VPH ToolKit (http://toolkit.vph-noe.eu/). VTME will enable sustainable curation of published vascular tissue simulations within the Chaste environment. It will be standards-based and infrastructure-supportive, adopting existing standards where they exist (SBML, CellML, MIRIAM, MIASE), and contributing to the development of new VPH standards (e.g., for vascular networks).

VPH NoE Repository

Please note that WP2 related documents and a private WP2 workspace is now available in the VPH NoE repository. To go to the VPH repository please click here.