Abstract
Reuse of mathematical models becomes increasingly important in systems biology as research moves toward large, multi-scale models composed of heterogeneous subcomponents. Currently, many models are not easily reusable due to inflexible or confusing code, inappropriate languages, or insufficient documentation. Best practice suggestions rarely cover such low-level design aspects. This gap could be filled by software engineering, which addresses those same issues for software reuse. We show that languages can facilitate reusability by being modular, human-readable, hybrid (i.e., supporting multiple formalisms), open, declarative, and by supporting the graphical representation of models. Modelers should not only use such a language, but be aware of the features that make it desirable and know how to apply them effectively. For this reason, we compare existing suitable languages in detail and demonstrate their benefits for a modular model of the human cardiac conduction system written in Modelica.
Highlights
As the understanding of biological systems grows, it becomes more and more apparent that their behavior cannot be reliably predicted without the help of mathematical models
In this article we share our experience with extending the Seidel-Herzel model (SHM) and generalize our findings from this example to expand on the idea of model engineering in three ways: First, we propose a list of desirable characteristics that make a model language suitable for building reusable multi-scale models
We chose one, namely Modelica, to no single language or even a small set of prescribed demonstrate the reasoning behind the characteristics, guidelines, languages is likely to cover all use cases which may arise in and language assessment using the example of the cardiac systems biology, especially when considering multi-class models, which combine entirely different model formalisms[7]
Summary
As the understanding of biological systems grows, it becomes more and more apparent that their behavior cannot be reliably predicted without the help of mathematical models. Sufficient criterion for the model to be reusable From these candidates, we chose one, namely Modelica, to no single language or even a small set of prescribed demonstrate the reasoning behind the characteristics, guidelines, languages is likely to cover all use cases which may arise in and language assessment using the example of the cardiac systems biology, especially when considering multi-class models, which combine entirely different model formalisms[7]. It can even be argued that it is beneficial if a component cannot be reused in an environment with different assumptions, since such a switch of assumptions will likely require more change than adding a variable to the interface For quick experimentation, it can be an advantage if the language allows connecting arbitrary internal variables of components, but published versions of a model should always have a clear interface concept to remain multitude of feedback loops, locating errors was very tedious with the original monolithic model. It was possible to reuse several components within the SHM: the parasympathetic and the sympathetic system share a base class that only leaves the sign of the baroreceptor influence open for definition and the four different release equations for norepinephrine and acetylcholine are governed by a common base class
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