Modelling Oscillatory Patterns in the Bovine Estrous Cycle with Boolean Delay Equations

Boolean delay equations (BDEs), with their relatively simple and intuitive mode of modelling, have been used in many research areas including, for example, climate dynamics and earthquake propagation. Their application to biological systems has been scarce and limited to the molecular level. Here, we derive and present two BDE models. One is directly derived from a previously published ordinary differential equation (ODE) model for the bovine estrous cycle, whereas the second model includes a modification of a particular biological mechanism. We not only compare the simulation results from the BDE models with the trajectories of the ODE model, but also validate the BDE models with two additional numerical experiments. One experiment induces a switch in the oscillatory pattern upon changes in the model parameters, and the other simulates the administration of a hormone that is known to shift the estrous cycle in time. The models presented here are the first BDE models for hormonal oscillators, and the first BDE models for drug administration. Even though automatic parameter estimation still remains challenging, our results support the role of BDEs as a framework for the systematic modelling of complex biological oscillators.