At first, several formal modeling approaches are examined regarding their suitability for describing biological models at multiple organizational levels. Thereby, diverse aspects are taken into account, such as the ability to describe dynamically changing hierarchical model structures and how upward and downward causation between different levels can be expressed. Based on the results of this study, a domain-specific language concept is developed to facilitate multilevel modeling in systems biology. The presented approach combines a rule-based modeling paradigm with dynamically nested model structures, attributed entities, and flexibly constrained reaction rates. Its expressive power, accessibility, and general usefulness for describing biological multilevel models are illustrated with the help of two exemplary case studies.
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