Continuous-time Markov models have been considered the best representation for the stochastic dynamics of ion channels for more than thirty years. For most single-channel data sets, several open and closed states are required for accurately representing the dynamics. However, each data point only shows if the channel is open or closed but not in which state it is. Consequently, some model structures are inherently overparameterized and therefore, in principle, unsuitable for representing any data - those models are called "nonidentifiable". As of this writing, it seems to be poorly understood which continuous-time Markov models are identifiable and which are not, therefore the unconscious use of a nonidentifiable model is a considerable concern. To address this problem, an improved variant of a recently published Markov-chain Monte Carlo method is presented. The algorithm is tested using test data as well as experimental data. We demonstrate that, opposed to a widely used maximum-likelihood estimator, it gives clear warning signs when a nonidentifiable model is used for fitting. Furthermore, for test data that was generated from a nonidentifiable model, the Markov-chain Monte Carlo results recover much more information from the data than maximum-likelihood estimation. © 2012 Biophysical Society.
Siekmann, I., Sneyd, J., & Crampin, E. J. (2012). MCMC can detect nonidentifiable models. Biophysical Journal, 103(11), 2275–2286. https://doi.org/10.1016/j.bpj.2012.10.024