Morpheus: A user-friendly simulation framework for multi-cellular systems biology

Computational modeling and simulation become increasingly important to analyze tissue morphogenesis. A number of corresponding software tools have been developed but require scientists to encode their models in an imperative programming language. Morpheus, on the other hand, is an extensible open-source software framework that is entirely based on declarative modeling. It uses the domain-specific language MorpheusML to define multicellular models through a user-friendly GUI and has since proven applicable by a much broader community, including experimentalists and trainees. We here present how MorpheusML and the open-source framework allow for rapid model prototyping and advanced scientific work-flows. MorpheusML provides a bio-mathematical language in which symbolic identifiers in mathematical expressions describe the dynamics of and coupling between the various model components. It represents the spatial and mechanical aspects of interacting cells in terms of the cellular Potts model formalism and follows the software design rule of separation of model from implementation, enabling model sharing, versioning and archiving. A numerical simulation is then composed by parsing the MorpheusML model definition and automatic scheduling of predefined components in the simulator. Moreover, Morpheus supports simulations based on experimental data, e.g. segmented cell configurations, and offers a broad set of analysis tools to extract features right during simulation. A rich c++ API allows to extend MorpheusML and the simulator with user-tailored plugins. Finally, we apply Morpheus and image-based modeling to study the regulatory mechanisms underlying liver tissue architecture and flatworm regeneration.