Automated maximum likelihood separation of signal from baseline in noisy quantal data.

Data recordings often include high-frequency noise and baseline fluctuations that are not generated by the system under investigation, which need to be removed before analyzing the signal for the system's behavior. In the absence of an automated method, experimentalists fall back on manual procedures for removing these fluctuations, which can be laborious and prone to subjective bias. We introduce a maximum likelihood formalism for separating signal from a drifting baseline plus noise, when the signal takes on integer multiples of some value, as in ion channel patch-clamp current traces. Parameters such as the quantal step size (e.g., current passing through a single channel), noise amplitude, and baseline drift rate can all be optimized automatically using the expectation-maximization algorithm, taking the number of open channels (or molecules in the on-state) at each time point as a hidden variable. Our goal here is to reconstruct the signal, not model the (possibly highly complex) underlying system dynamics. Thus, our likelihood function is independent of those dynamics. This may be thought of as restricting to the simplest possible hidden Markov model for the underlying channel current, in which successive measurements of the state of the channel(s) are independent. The resulting method is comparable to an experienced human in terms of results, but much faster. FORTRAN 90, C, R, and JAVA codes that implement the algorithm are available for download from our website.