Standard virtual biological parts: a repository of modular modeling components for synthetic biology.

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.

A method for visualizing CellML models.

MOTIVATION: The Physiome Project was established in 1997 to develop tools to facilitate international collaboration in the physiological sciences and the sharing of biological models and experimental data. The CellML language was developed to represent and exchange mathematical models of biological processes. CellML models can be very complicated, making it difficult to interpret the underlying physical and biological concepts and relationships captured/described in the mathematical model. RESULTS: To address this issue a set of ontologies was developed to explicitly annotate the biophysical concepts represented in the CellML models. This article presents a framework that combines a visual language, together with CellML ontologies, to support the visualization of the underlying physical and biological concepts described by the mathematical model and also their relationships with the CellML model. Automated CellML model visualization assists in the interpretation of model concepts and facilitates model communication and exchange between different communities.

Facilitating modularity and reuse: guidelines for structuring CellML 1.1 models by isolating common biophysical concepts.

The CellML language was developed in response to the need for a high-level language to represent and exchange mathematical models of biological processes. The flexible structure of CellML allows modellers to construct mathematical models of the same biological system in many different ways. However, some modelling styles do not naturally lead to clear abstractions of the biophysical concepts and produce CellML models that are hard to understand and from which it is difficult to isolate parts that may be useful for constructing other models. In this article, we advocate building CellML models which isolate common biophysical concepts and, using these, to build mathematical models of biological processes that provide a close correspondence between the CellML model and the underlying biological process. Subsequently, models of higher complexity can be constructed by reusing these modularized CellML models in part or in whole. Development of CellML models that best describe the underlying biophysical concepts thus avoids the need to code models from scratch and enhances the extensibility, reusability, consistency and interpretation of the models.

Modelling biological modularity with CellML.

In recent years advances in the construction of mathematical models of biological systems have yielded an array of valuable constructs. The authors seek to provide a 'leading practice' method for implementing modularised kinetic mass-action models in order to obtain a number of advantages in model construction, validation and derived insights. The authors advocate the consideration of 'accounting cycles' or 'chains' to define 'functional' components and the separate consideration of 'messenger' components for mobile or diffusive molecular species. From a conceptual modularisation the authors illustrate, with an example drawn from signal transduction, a component-based formulation in the model exchange format cellular modelling markup language (CellML) 1.1 - demonstrating loose coupling between functionally-focused reusable components. Finally, the authors discuss the dilemmas associated with modelling protein-to-protein interactions, and the vision for using future CellML enhancements to resolve potential duplications when combining independently developed models.