“…In return for stable and high-quality results in MDMC, however, it is necessary to solve coupled master equations, which require sophisticated schemes to optimize model parameters. Unfortunately, the EM algorithm, which was utilized in the original formulation [23,24], does not always find the optimal structures because it is sensitive to initial values of the parameters. Hence, elaboration of the optimization algorithm is highly desired to make full use of the powerful modeling of MDMC.…”