Characteristics of mathematical modeling languages that facilitate model reuse in systems biology: a software engineering perspective

Reproducible, understandable models that can be reused and combined to true multi-scale systems are required to solve the present and future challenges of systems biology. However, many mathematical models are still built for a single purpose and reusing them in a different context is challenging. To overcome these challenges model quality needs to be addressed at the (software-)engineering level. Instead of just declaring standard modeling languages, researchers need to be aware of the characteristics that make these languages desirable and they need to utilize them consistently. We therefore propose a list of required characteristics and provide guidelines how to incorporate them in a model: In our opinion, a modeling language used for models in systems biology should be modular, human-readable, hybrid (i.e. support multiple formalisms), open-source, declarative, and allow to represent models graphically. We demonstrate the benefits of these characteristics by translating a monolithic model of the human cardiac conduction system to a modular version and extending it with a trigger for premature ventricular contractions. For this task we use the modeling language Modelica, that has all the aforementioned characteristics, but is not well known in systems biology. Our example illustrates how each characteristic can have a substantial effect on the quality and reusability of the resulting model. Together they facilitate and simplify the creation and especially the extension of the modular model. We therefore recommend to consider these guidelines when choosing a programming language for any biological modeling task.