Qualitative Analysis of Mammalian Circadian Oscillations: Cycle Dynamics and Robustness.

In asynchronous Boolean models, periodic solutions are represented by terminal strongly connected graphs, which are typically composed of hundreds of states and transitions. For biological systems, it becomes a challenging task to compare such mathematical objects with biological knowledge, or interpret the transitions inside an attractor in terms of the sequence of events in a biological cycle. A recent methodology generates summary graphs to help visualizing complex asynchronous attractors and order the dynamic progression based on known biological data. In this article we apply this method to a Boolean model of the mammalian circadian clock, for which the summary graph recovers the main phases of the cycle, in the expected order. It also provides a detailed view of the attractor, suggesting improvements in the design of the model’s logical rules and highlighting groups of transitions that are essential for the attractor’s robustness.