MOTIVATION: The need for the automated computational design of genetic circuits is becoming increasingly apparent with the advent of ever more complex and ambitious synthetic biology projects. Currently, most circuits are designed through the assembly of models of individual parts such as promoters, ribosome binding sites and coding sequences. These low level models are combined to produce a dynamic model of a larger device that exhibits a desired behaviour. The larger model then acts as a blueprint for physical implementation at the DNA level. However, the conversion of models of complex genetic circuits into DNA sequences is a non-trivial undertaking due to the complexity of mapping the model parts to their physical manifestation. Automating this process is further hampered by the lack of computationally tractable information in most models. RESULTS: We describe a method for automatically generating DNA sequences from dynamic models implemented in CellML and Systems Biology Markup Language (SBML). We also identify the metadata needed to annotate models to facilitate automated conversion, and propose and demonstrate a method for the markup of these models using RDF. Our algorithm has been implemented in a software tool called MoSeC. AVAILABILITY: The software is available from the authors' web site http://research.ncl.ac.uk/synthetic_biology/downloads.html.

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/.

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.

MOTIVATION: Fabrication of synthetic biological systems is greatly enhanced by incorporating engineering design principles and techniques such as computer-aided design. To this end, the ongoing standardization of biological parts presents an opportunity to develop libraries of standard virtual parts in the form of mathematical models that can be combined to inform system design. RESULTS: We present an online Repository, populated with a collection of standardized models that can readily be recombined to model different biological systems using the inherent modularity support of the CellML 1.1 model exchange format. The applicability of this approach is demonstrated by modeling gold-medal winning iGEM machines. AVAILABILITY AND IMPLEMENTATION: The Repository is available online as part of http://models.cellml.org. We hope to stimulate the worldwide community to reuse and extend the models therein, and contribute to the Repository of Standard Virtual Parts thus founded. Systems Model architecture information for the Systems Model described here, along with an additional example and a tutorial, is also available as Supplementary information. The example Systems Model from this manuscript can be found at http://models.cellml.org/workspace/bugbuster. The Template models used in the example can be found at http://models.cellml.org/workspace/SVP_Templates200906.