Architecture of ML-Rules and the JAMES II framework. (A) Basic overview of the JAMES II modeling and simulation framework architecture. The core defines a basic set of plug-in types and plug-ins needed to run experiments and also provides a rich set of tools reusable in other plug-ins. Also part of the core, the registry is responsible for managing plug-in types and plug-ins, and the experimentation layer carries out simulation experiments, e.g. simple simulation runs, parameter scans, optimizations and sensitivity analyses. (B) Simplified overview of the main ML-Rules plug-ins and how they are interconnected. Arrows show flow of data.