Morpheus: A user-friendly and extensible simulation framework supporting declarative modeling
Version 1

Computational modeling and simulation become increasingly important for Systems Medicine. A number of corresponding software tools have been developed but require scientists to encode their models in an imperative programming language. Morpheus [1,2], 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. MorpheusML [3] and the open-source framework [4] allow for advanced scientific workflows.
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 can represent the spatial aspects of interacting cells and follows the software design rule of separation of model from implementation, enabling model sharing, versioning and archiving [3].
A numerical simulation is then composed by 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.
As an example, we apply Morpheus to study the regulatory crosstalk of Wnt and Hh pathways underlying the spatial metabolic zonation of liver tissue [5].

1 Starruß et al. Morpheus: a user-friendly modeling environment for multiscale and multicellular systems
biology. Bioinformatics 30, 1331, 2014.
2 Homepage:
3 Model repository:
4 Open source code:
5 Kolbe et al., Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism
of the Adult Liver in Mice and Human. Cell Reports 29, 4553, 2019.


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