Applying hidden Markov models to the analysis of single ion channel activity

Hidden Markov models have recently been used to model single ion channel currents as recorded with the patch clamp technique from cell membranes. The estimation of hidden Markov models parameters using the forward-backward and Baum-Welch algorithms can be performed at signal to noise ratios that are too low for conventional single channel kinetic analysis; however, the application of these algorithms relies on the assumptions that the background noise be white and that the underlying state transitions occur at discrete times. To address these issues, we present an "H-noise" algorithm that accounts for correlated background noise and the randomness of sampling relative to transitions. We also discuss three issues that arise in the practical application of the algorithm in analyzing single channel data. First, we describe a digital inverse filter that removes the effects of the analog antialiasing filter and yields a sharp frequency roll-off. This enhances the performance while reducing the computational intensity of the algorithm. Second, the data may be contaminated with baseline drifts or deterministic interferences such as 60-Hz pickup. We propose an extension of previous results to consider baseline drift. Finally, we describe the extension of the algorithm to multiple data sets.