The Physiome Model Repository and the link to bioinformatics¶

The Physiome Model Repository (PMR) [LCPF08] is the main online repository for the IUPS Physiome Project, providing version and access controlled repositories, called workspaces, for users to store their data. Currently there are over 700 public workspaces and many private workspaces in the repository. PMR also provides a mechanism to create persistent access to specific revisions of a workspace, termed exposures. Exposure plugins are available for specific types of data (e.g. CellML or FieldML documents) which enable customizable views of the data when browsing the repository via a web browser, or an application accessing the repository’s content via web services.

More complete documentation describing how to use PMR is available in the PMR documentation: https://models.physiomeproject.org/docs.

The CellML models on models.physiomeproject.org are listed under 20 categories, shown below: (numbers of exposures in each category are given besides the bar graph, correct as at early 2016)

Browse by category

Calcium Dynamics

image_variable_node_140 140

Cardiovascular Circulation

image_variable_node_60 60

Cell Cycle

image_variable_node_38 38

Cell Migration

image_variable_node_2 2

Circadian Rhythms

image_variable_node_22 22

Electrophysiology

image_variable_node_230 230

Endocrine

image_variable_node_60 60

Excitation-Contraction Coupling

image_variable_node_22 22

Gene Regulation

image_variable_node_12 12

Hepatology

image_variable_node_29 29

Immunology

image_variable_node_55 55

Ion transport

image_variable_node_13 13

Mechanical Constitutive Laws

image_variable_node_19 19

Metabolism

image_variable_node_86 86

Myofilament Mechanics

image_variable_node_22 22

Neurobiology

image_variable_node_33 33

pH regulation

image_variable_node_2 2

PKPD

image_variable_node_11 11

Signal Transduction

image_variable_node_120 120

Synthetic Biology

image_variable_node_6 6

Note that searching of models can be done anywhere on the site using the search box on the upper right hand corner. An important benefit of ensuring that the models on the PMR are annotated is that models can then be retrieved by a web-search using any of the annotated terms in the models.

To illustrate the features of PMR, click on the Hund, Rudy 2004 (Basic) model in the alphabetic listing of models under the Electrophysiology category.

PMR exposure page for the Hund-Rudy 2004 model

Fig. 39 The Physiome Model Repository exposure page for the basic Hund-Rudy 2004 model.¶

The section labelled ‘Model Structure’ contains the journal paper abstract and often a diagram of the model[1]. This is shown for the Hund-Rudy 2004 model in Fig. 40. This model, with over 22 separate protein model components, is also a good example of why it is important to build models from modular components [CMEJ08], and in particular the individual ion channels for electrophysiology models.

Hund 2004 shematic diagram

Fig. 40 A diagrammatic representation of the Hund-Rudy 2004 model.¶

There is a list of ‘Views Available’ for the CellML model on the right hand side of the exposure page. The function of each of these views is as follows:

Views Available

Documentation - Takes you to the main exposure page.

Model Metadata - Lists metadata including authors, title, journal, Pubmed ID and model annotations.

Model Curation - Provides the curation status of the model. Note: this is soon to be updated.

Mathematics - Displays all the mathematical equations contained in the model.

Generated Code - Various codes (C, C-IDA, F77, MATLAB or Python) generated from the model.

Cite this model - Provides details on how to cite use of the CellML model.

Source view - Gives a full listing of the XML code for the model.

Launch with OpenCOR - Opens the model (or simulation experiment) in OpenCOR.

Note that CellML models are available under a Creative Commons Attribution 3.0 Unported License[2]. This means that you are free to:

  • Share — copy and redistribute the material in any medium or format

  • Adapt — remix, transform, and build upon the material

for any purpose, including commercial use.

The next stage of content development for PMR is to provide a list of the modular components of these models each with their own exposure. For example, models for each of the individual ion channels used in the publication-based electrophysiological models will be available as standalone models that can then be imported as appropriate into a new composite model. Similarly for enzymes in metabolic pathways and signalling complexes in signalling pathways, etc. Some examples of these protein modules are:

Sodium/hydrogen exchanger 3 https://models.physiomeproject.org/e/236/

Thiazide-sensitive Na-Cl cotransporter https://models.physiomeproject.org/e/231/

Sodium/glucose cotransporter 1 https://models.physiomeproject.org/e/232/

Sodium/glucose cotransporter 2 https://models.physiomeproject.org/e/233/

Note that in each case, as well as the CellML-encoded mathematical model, links are provided (see Fig. 41) to the UniProt Knowledgebase for that protein, and to the Foundational Model of Anatomy (FMA) ontology (via the EMBLE-EBI Ontology Lookup Service) for information about tissue regions relevant to the expression of that protein (e.g. Proximal convoluted tubule, Apical plasma membrane; Epithelial cell of proximal tubule; Proximal straight tubule). Similar facilities are available for SMBL-encoded biochemical reaction models through the Biomodels database [AYY].

Thiazide-sensitive Na-Cl cotransporter workspace

Fig. 41 The PMR workspace for the Thiazide-sensitive Na-Cl cotransporter. Bioinformatic data for this model is accessed via the links under the headings highlight by the arrows and include Protein (labelled A) and the model Location (labelled B). Other information is as already described for the Hund-Rudy 2004 model.¶


Footnotes

[1]

These are currently hand drawn SVG diagrams but the plan is to automatically generate them from the model annotation and also (at some stage!) to animate them as the model is executed.

[2]

https://creativecommons.org/licenses/by/3.0/

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Introducing OpenCOR, PMR, and CellML

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Navigation

  • Background to the VPH-Physiome project
  • Install and launch OpenCOR
  • Create and run a simple CellML model: editing and simulation
  • Open an existing CellML file from a local directory or the Physiome Model Repository
  • A simple first order ODE
  • The Lorenz attractor
  • A model of ion channel gating and current: Introducing CellML units
  • A model of the potassium channel: Introducing CellML components and connections
  • A model of the sodium channel: Introducing CellML encapsulation and interfaces
  • A model of the nerve action potential: Introducing CellML imports
  • A model of the cardiac action potential: Importing units and parameters
  • Code generation
  • Model annotation
  • The Physiome Model Repository and the link to bioinformatics
  • Using PMR with OpenCOR
  • SED-ML, functional curation and Web Lab
  • Using OpenCOR with Python (beta)
  • Speed comparisons with MATLAB
  • References

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  • Documentation overview
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