Tommy Yu

The Physiome Model Repository 2

MOTIVATION The Physiome Model Repository 2 (PMR2) software was created as part of the IUPS Physiome Project (Hunter and Borg, 2003), and today it serves as the foundation for the CellML model repository. Key advantages brought to the end user by PMR2 include: facilities for model exchange, enhanced collaboration and a detailed change history for each model. AVAILABILITY PMR2 is available under an open source license at http://www.cellml.org/tools/pmr/; a fully functional instance of this software can be accessed at http://models.physiomeproject.org/.

CellML metadata standards, associated tools and repositories

The development of standards for encoding mathematical models is an important component of model building and model sharing among scientists interested in understanding multi-scale physiological processes. CellML provides such a standard, particularly for models based on biophysical mechanisms, and a substantial number of models are now available in the CellML Model Repository. However, there is an urgent need to extend the current CellML metadata standard to provide biological and biophysical annotation of the models in order to facilitate model sharing, automated model reduction and connection to biological databases. This paper gives a broad overview of a number of new developments on CellML metadata and provides links to further methodological details available from the CellML website.

Sharing and reusing cardiovascular anatomical models over the Web: a step towards the implementation of the virtual physiological human project.

Sharing and reusing anatomical models over the Web offers a significant opportunity to progress the investigation of cardiovascular diseases. However, the current sharing methodology suffers from the limitations of static model delivery (i.e. embedding static links to the models within Web pages) and of a disaggregated view of the model metadata produced by publications and cardiac simulations in isolation. In the context of euHeart—a research project targeting the description and representation of cardiovascular models for disease diagnosis and treatment purposes—we aim to overcome the above limitations with the introduction of euHeartDB, a Web-enabled database for anatomical models of the heart. The database implements a dynamic sharing methodology by managing data access and by tracing all applications. In addition to this, euHeartDB establishes a knowledge link with the physiome model repository by linking geometries to CellML models embedded in the simulation of cardiac behaviour. Furthermore, euHeartDB uses the exFormat—a preliminary version of the interoperable FieldML data format—to effectively promote reuse of anatomical models, and currently incorporates Continuum Mechanics, Image Analysis, Signal Processing and System Identification Graphical User Interface (CMGUI), a rendering engine, to provide three-dimensional graphical views of the models populating the database. Currently, euHeartDB stores 11 cardiac geometries developed within the euHeart project consortium.

FieldML, a proposed open standard for the Physiome project for mathematical model representation

The FieldML project has made significant progress towards the goal of addressing the need to have open standards and open source software for representing finite element method (FEM) models and, more generally, multivariate field models, such as many of the models that are core to the euHeart project and the Physiome project. FieldML version 0.5 is the most recently released format from the FieldML project. It is an XML format that already has sufficient capability to represent the majority of euHeart’s explicit models such as the anatomical FEM models and simulation solution fields. The details of FieldML version 0.5 are presented, as well as its limitations and some discussion of the progress being made to address these limitations.

The Open Physiology workflow: modeling processes over physiology circuitboards of interoperable tissue units.

A key challenge for the physiology modeling community is to enable the searching, objective comparison and, ultimately, re-use of models and associated data that are interoperable in terms of their physiological meaning. In this work, we outline the development of a workflow to modularize the simulation of tissue-level processes in physiology. In particular, we show how, via this approach, we can systematically extract, parcellate and annotate tissue histology data to represent component units of tissue function. These functional units are semantically interoperable, in terms of their physiological meaning. In particular, they are interoperable with respect to [i] each other and with respect to [ii] a circuitboard representation of long-range advective routes of fluid flow over which to model long-range molecular exchange between these units. We exemplify this approach through the combination of models for physiology-based pharmacokinetics and pharmacodynamics to quantitatively depict biological mechanisms across multiple scales. Links to the data, models and software components that constitute this workflow are found at http://open-physiology.org/.

The VPH-Physiome Project: Standards, tools and databases for multi-scale physiological modelling

The VPH/Physiome project is developing tools and model databases for computational physiology based on three primary model encoding standards: CellML, SBML and FieldML. For the modelling community these standards are the equivalent of the DICOM standard for the clinical imaging community and it is important that the tools adhere to these standards to ensure that models from different groups can be curated, annotated, reused and combined. This chapter discusses the development and use of the VPH/Physiome standards, tools and databases, and also discusses the minimum information standards and ontology-based metadata standards that are complementary to the markup language standards. Data standards are not as well developed as the model encoding standards (with the DICOM standard for medical image encoding being the outstanding exception) but one new data standard being developed as part of the VPH/Physiome suite is BioSignalML and this is described here also. The PMR2 (Physiome Model Repository 2) database for CellML and FieldML files is also described, together with the Application Programming Interfaces (APIs) that facilitate access to the models from the visualization (cmgui and GIMIAS) or computational (OpenCMISS, OpenCell/OpenCOR and other) software.

A Distributed Revision Control System for Collaborative Development of Quantitative Biological Models

With CellML 1.0, models are encapsulated completely by a single file. CellML 1.1 now allows a model to be decomposed into many smaller files that can represent a single component of a model that can be reused by other related models. Unfortunately, managing even just tens of models with hundreds of shared component files may be a daunting task. For instance, updating a shared component for one model may break another, or it may be difficult to locate the correct component to be included into a model that one may be building.

Distributed Model Construction with Virtual Parts

Here three models for a simple genetic device are constructed using modular mathematical models. The models are stored in an online system (the Physiome Model Repository) with distributed source and access control, demonstrating a collaborative method for creating mathematical models from reusable components.