COPASI - Open source software for advanced biochemical network modelling

Modeling and simulation of biochemical networks has become an essential activity to aid in the understanding of cellular behavior and to facilitate quantitative interpretation of modern experiments. A new approach to biological sciences, "systems biology", is being advocated which combines modeling, simulation and quantitative experiments. Bioscience research is becoming increasingly dependent on construction and simulation of computational models. However, the technical aspects of modeling and simulation are overwhelming to a large number of biomedical researchers, and what is needed is a software application that is capable of providing the appropriate numerical algorithms shielded by a user interface that aides the researcher to conduct the required simulations. We address this need here with continuing development of our software COPASI, which is already widely used in the research community. This project will also provide support to the vibrant community of COPASI users in the UK bioscience research community.

In this project we will extend the capabilities of COPASI: we will add means to simulate models with explicit time delays; provide a mechanism for easy calculation of summaries of entire simulations and groups of simulations; incorporate a new feature that will allow researchers, for the first time, to be able to navigate the entire history of a model, such that the reasons for changes that took place are formally identified, as well as decisions on the model structure.

The project will also improve and extend the software's interoperability and standards compliance. This is extremely important in order to allow bioscience researchers to freely exchange data and models. COPASI will be equipped to facilitate users to create and read simulation information in SED-ML format, it will be enabled to save and read simulation and experimental result in the SBRML format, and it will support the proposed SBML Level 3 (a format to represent biological models).

We will keep developing COPASI using formal software development methodologies that promote quality. An existing testing plan will be continued and expanded, including appropriate collection of models designed to test the various functions of the software; bug reports will be collected and fixed; suggestions for improvement will be collected from users and followed through.

Finally we aim to support the bioscience community in their use of COPASI and modelling and simulation in general. Online support will be developed and maintained, such as video tutorials, a web support forum, and a user manual. We will hold COPASI User Workshops twice yearly, where bioscience researchers learn to use new features of the software, apply it to their problems with help from the development team, and present their suggestions for improvement. We will also provide tutorials at popular systems biology conferences.

We will support the bioscience community, primarily in the UK but also globally, by maintaining and improving the COPASI software resource, a software package for modelling, simulation and analysis of biochemical networks. The programme of work includes a) expansion of the capabilities of the software, b) improvement of the user interface, c) enlarged support for systems biology standards, d) maintenance of the software, including testing and release of new versions, e) outreach and training activities.

We will add algorithms for integrating delay differential equations, which are needed when explicit delays are required in a model. To enable easy calculation of numerical summaries of entire simulations and groups of simulations, we will create a framework that allows their selection from a predefined set. These summaries will be available for optimisation and sensitivity analysis, allowing for closed loop operations that would otherwise be impossible. We will improve the user interface in response to user requirements collected online in the forum and in person in user workshops. We will continue to maintain the source code, identifying and fixing bugs, improving performance based on profiling results, and carrying out routine testing with formal test suites. We will develop a new feature for assisting with management of models; this will include provenance capture, version management, model differencing, and model search. Outreach activities will be in the form of a bi-annual user workshop and online video tutorials. User support will be through an online forum (already with >950 subscribers). We will maintain a web services access point for COPASI functionality to allow others to develop software that uses this web services API. We will expand the range of systems biology standards supported, to include SBRML format for results and SED-ML for tasks. We will create code to support SBML level 3 packages, which are optional features of this widely used standard.

This project is for the maintenance and further development of the COPASI resource, an open source software for modelling and simulation of biochemical networks.

Who will benefit?

The beneficiaries of this research are scientists and teams of scientists that use computational modelling and simulation of biochemical networks as part of their research. This includes academic researchers, research students, and scientists from industries such as pharmaceuticals, biotechnology, agriculture, cosmetics and health. Furthermore, the methodologies and software will also benefit the regulatory agencies in the same areas because modelling and simulation are starting to be used as part of the required pre-approval documentation.

How will they benefit?

The benefits from the outputs of this research will impact the way in which the beneficiaries carry out modelling of biochemical systems, allowing them to perform in silico experiments. This is an important part of all systems approaches. The COPASI resource is also an important tool in the replacement, refinement and reduction of research using animals (3Rs), where computational simulations can be carried out to optimally plan experiments in order to reduce use of animals.

The improvements planned for the software will allow researchers to be more efficient at using modelling and simulation. They will now be able to model systems where there are explicit time delays, which includes circadian rhythms that have a role in plant growth efficiency (food security). A new framework to help manage models will have an impact in how the beneficiaries are able to document the provenance of models, something that will be necessary for using simulation results in regulatory processes.

The COPASI software is used as a component of other computational resources for biology, such as the Systems Biology Software Infrastructure (from the Centre for Systems Biology in Edinburgh), or the FLAME multiscale simulation system (University of Sheffield). Because of this the impact of COPASI is wider than just the set of researchers that are direct users; indeed it impacts also on the users of those other packages.

Since COPASI is one of the most used systems of its type worldwide, its maintenance and further development helps keep UK Science in a worldwide leading position in the area of computational modelling of biological systems. UK industries adopting the methods or software developed here will increase their research effectiveness and thus this will contribute to their competitiveness (as documented in letters of support).