Revision history aware repositories of computational models of biological systems.

BACKGROUND: Building repositories of computational models of biological systems ensures that published models are available for both education and further research, and can provide a source of smaller, previously verified models to integrate into a larger model. One problem with earlier repositories has been the limitations in facilities to record the revision history of models. Often, these facilities are limited to a linear series of versions which were deposited in the repository. This is problematic for several reasons. Firstly, there are many instances in the history of biological systems modelling where an 'ancestral' model is modified by different groups to create many different models. With a linear series of versions, if the changes made to one model are merged into another model, the merge appears as a single item in the history. This hides useful revision history information, and also makes further merges much more difficult, as there is no record of which changes have or have not already been merged. In addition, a long series of individual changes made outside of the repository are also all merged into a single revision when they are put back into the repository, making it difficult to separate out individual changes. Furthermore, many earlier repositories only retain the revision history of individual files, rather than of a group of files. This is an important limitation to overcome, because some types of models, such as CellML 1.1 models, can be developed as a collection of modules, each in a separate file. The need for revision history is widely recognised for computer software, and a lot of work has gone into developing version control systems and distributed version control systems (DVCSs) for tracking the revision history. However, to date, there has been no published research on how DVCSs can be applied to repositories of computational models of biological systems. RESULTS: We have extended the Physiome Model Repository software to be fully revision history aware, by building it on top of Mercurial, an existing DVCS. We have demonstrated the utility of this approach, when used in conjunction with the model composition facilities in CellML, to build and understand more complex models. We have also demonstrated the ability of the repository software to present version history to casual users over the web, and to highlight specific versions which are likely to be useful to users. CONCLUSIONS: Providing facilities for maintaining and using revision history information is an important part of building a useful repository of computational models, as this information is useful both for understanding the source of and justification for parts of a model, and to facilitate automated processes such as merges. The availability of fully revision history aware repositories, and associated tools, will therefore be of significant benefit to the community.

An overview of the CellML API and its implementation.

BACKGROUND: CellML is an XML based language for representing mathematical models, in a machine-independent form which is suitable for their exchange between different authors, and for archival in a model repository. Allowing for the exchange and archival of models in a computer readable form is a key strategic goal in bioinformatics, because of the associated improvements in scientific record accuracy, the faster iterative process of scientific development, and the ability to combine models into large integrative models.However, for CellML models to be useful, tools which can process them correctly are needed. Due to some of the more complex features present in CellML models, such as imports, developing code ab initio to correctly process models can be an onerous task. For this reason, there is a clear and pressing need for an application programming interface (API), and a good implementation of that API, upon which tools can base their support for CellML. RESULTS: We developed an API which allows the information in CellML models to be retrieved and/or modified. We also developed a series of optional extension APIs, for tasks such as simplifying the handling of connections between variables, dealing with physical units, validating models, and translating models into different procedural languages.We have also provided a Free/Open Source implementation of this application programming interface, optimised to achieve good performance. CONCLUSIONS: Tools have been developed using the API which are mature enough for widespread use. The API has the potential to accelerate the development of additional tools capable of processing CellML, and ultimately lead to an increased level of sharing of mathematical model descriptions.

Minimum information requested in the annotation of biochemical models (MIRIAM).

Most of the published quantitative models in biology are lost for the community because they are either not made available or they are insufficiently characterized to allow them to be reused. The lack of a standard description format, lack of stringent reviewing and authors' carelessness are the main causes for incomplete model descriptions. With today's increased interest in detailed biochemical models, it is necessary to define a minimum quality standard for the encoding of those models. We propose a set of rules for curating quantitative models of biological systems. These rules define procedures for encoding and annotating models represented in machine-readable form. We believe their application will enable users to (i) have confidence that curated models are an accurate reflection of their associated reference descriptions, (ii) search collections of curated models with precision, (iii) quickly identify the biological phenomena that a given curated model or model constituent represents and (iv) facilitate model reuse and composition into large subcellular models.

CellML: its future, present and past.

Advances in biotechnology and experimental techniques have lead to the elucidation of vast amounts of biological data. Mathematical models provide a method of analysing this data; however, there are two issues that need to be addressed: (1) the need for standards for defining cell models so they can, for example, be exchanged across the World Wide Web, and also read into simulation software in a consistent format and (2) eliminating the errors which arise with the current method of model publication. CellML has evolved to meet these needs of the modelling community. CellML is a free, open-source, eXtensible markup language based standard for defining mathematical models of cellular function. In this paper we summarise the structure of CellML, its current applications (including biological pathway and electrophysiological models), and its future development--in particular, the development of toolsets and the integration of ontologies.

The CellML 1.1 Specification.

This document specifies CellML 1.1, an XML-based language for describing and exchanging models of cellular and subcellular processes. MathML embedded in CellML documents is used to define the underlying mathematics of models. Models consist of a network of reusable components, each with variables and equations manipulating those variables. Models may import other models to create systems of increasing complexity. Metadata may be embedded in CellML documents using RDF.

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.

Toward a curated CellML model repository.

With the development of standards for the description of experimental data and mathematical models of physiological processes has come the advent of publicly accessible repositories of such descriptions. To make these repositories acceptable to the community, the descriptions contained therein must be curated to provide an indication of how accurately the standard description represents the actual experimental data or mathematical model. We define here a curation method for CellML encoded models and propose a model repository workflow using such curation within the CellML model repository.