Fully Automatic Multiresolution Idealization for Filtered Ion Channel Recordings: Flickering Event Detection

Abstract

We propose a new model-free segmentation method, JULES, which combines recent statistical multiresolution techniques with local deconvolution for idealization of ion channel recordings. The multiresolution criterion takes into account scales down to the sampling rate enabling the detection of flickering events, i.e., events on small temporal scales, even below the filter frequency. For such small scales the deconvolution step allows for a precise determination of dwell times and, in particular, of amplitude levels, a task which is not possible with common thresholding methods. This is confirmed theoretically and in a comprehensive simulation study. In addition, JULES can be applied as a preprocessing method for a refined hidden Markov analysis. Our new methodology allows us to show that gramicidin A flickering events have the same amplitude as the slow gating events. JULES is available as an R function jules in the package clampSeg.

High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB

“…4,26 However, the filter length used by automated analysis methods limits the detection of short blockage events beyond the filter resolution, which means that relevant data is discarded as noise (missed events). Therefore, to be able to detect the short blockage events shown in μ s using a missed event correction 22 . This improves previously achieved detection limits of about 50 μ s 4,31,32 , which would not be sufficient for the subsequent analysis.…”

“…However, these methods are based on the assumption of a HMM throughout the analysis and more importantly, their results are heavily influenced by model violations. A more detailed discussion and comparison of these methods can be found in the introduction of Pein et al 22 . Additionally, details of the models and the corresponding statistical analysis are given in the supporting information.…”

“…Model-free idealizations are obtained by JULES. 22 Its combination of multiresolution techniques and local deconvolution allows a precise idealisation of events below the filter length; in particular amplitudes and residence times that are smoothed by the filter are reconstructed with high precision (Fig. S3).…”

“…In this study, we demonstrate that a combination of high-resolution singlechannel electrophysiology, novel high-sensitivity electrophysiology analysis methods, 22 and atomistic molecular dynamics simulations allowed us to reveal in structural detail a drug-channel binding interaction that is too weak to be captured by X-ray crystallography. We set out to investigate the interaction between ampicillin and PorB from Neisseria meningitidis, the pathogen that causes bacterial meningitis.…”

The OpenPicoAmp-100k : an open-source high performance amplifier for single channel recording in planar lipid bilayers

“…At last, special post-recording denoising and current idealization techniques also deserve attention when working with high bandwidth ion channel data. These techniques include discrete wavelet transforms such as demonstrated in Figure 7 [see also 1,20,21], idealizations based on hidden Markov model with Baum-Welch algorithms of parameters estimation [18] or modelfree algorithms [14].…”