Introduction:
Computational methods are applied with increasing success to the analysis of complex biological systems. However, their adoption is sometimes made difficult by requiring prior knowledge about the foundations of such methods, which often come from a different branch of science. The software ANIMO (Analysis of Networks with Interactive MOdel ing, [1]) allows the tissue engineer to add dynamic behavior to tradi tional static models of signaling events. We use ANIMO to optimize cartilage tissue engineering.
Materials and methods:
Starting from a signaling network as tradition ally represented in books, ANIMO allows biologists to take advantage of their expertise, enriching the symbolic description with quantitative parameters. The underlying computational model is based on the for malism of Timed Automata [2] and is automatically generated and analyzed by ANIMO. Implementation as a Cytoscape [3] plugin makes the interface intuitively usable: for example, an existing network topol ogy can be extended with few mouse clicks, adding new nodes and edges. The use of ANIMO does not require detailed knowledge of the underlying formalism of the model.
Results:
Figure 1 shows the user interface of Cytoscape enriched by ANIMO: simulation runs are shown in form of graphs (on the right). The course of a simulation is mirrored in the network (left) thanks to a usermovable slider under the corresponding graph: different colors indicate different activity levels as shown in the Legend. The Timed Automata model is automatically produced by ANIMO from the net work defined in the Cytoscape interface, completely transparently to the user. The models can also be analyzed with the technique of model checking, thanks to the application of the powerful tool UPPAAL [4]. Also this analysis occurs behind the scenes, presenting the user with a querying interface based on human language.
Discussion and conclusions:
The interactive nature of ANIMO combined with the modeling power of the underlying formalism allows the tissue engineer to create and explore executable models [5] of biological net works, helping to derive hypotheses and to plan wetlab experiments in a familiar environment. To validate ANIMO, we will present a small model of chondrocyte response to IL1b and Wnt signaling, and show how ANIMO can opti mize conditions for cartilage tissue engineering.