KiSSim: Predicting off-targets from structural similarities in the kinome

Protein kinases are among the most important drug targets because their dysregulation can cause cancer, inflammatory, and degenerative diseases. Developing selective inhibitors is challenging due to the highly conserved binding sites across the roughly 500 human kinases. Thus, detecting subtle similarities on a structural level can help to explain and predict off-targets among the kinase family. Here, we present the kinase-focused and subpocket-enhanced KiSSim fingerprint (Kinase Structural Similarity). The fingerprint builds on the KLIFS pocket definition, composed of 85 residues aligned across all available protein kinase structures, which enables residue-by-residue comparison without a computationally expensive alignment. The residues' physicochemical and spatial properties are encoded within their structural context including key subpockets at the hinge region, the DFG motif, and the front pocket. Since structure was found to contain information complementary to sequence, we used the fingerprint to calculate all-against-all similarities within the structurally covered kinome. Thereby, we could identify off-targets that are unexpected if solely considering the sequence-based kinome tree grouping; for example, Erlobinib’s known kinase off-targets SLK and LOK show high similarities to the key target EGFR (TK group) though belonging to the STE group. KiSSim reflects profiling data better or at least as well as other approaches such as KLIFS pocket sequence identity, KLIFS interaction fingerprints (IFPs), or SiteAlign. To rationalize observed (dis)similarities, the fingerprint values can be visualized in 3D by coloring structures with residue and feature resolution. We believe that the KiSSim fingerprint is a valuable addition to the kinase research toolbox to guide off-target and polypharmacology prediction. The method is distributed as an open-source Python package on GitHub and as conda package: https://github.com/volkamerlab/kissim

A Position Sensing Glove to Aid Ankle-Foot Orthosis Diagnosis and Treatment

A position sensing glove called SmartScan, which creates a 3D virtual model of a real object, is presented. The data from the glove is processed by a volume minimization algorithm to validate the position sensor data. This allows only data from the object’s surface to be retained. The data validation algorithm allows the user to progressively improve an image by repeatedly moving their hand over the object. In addition, the user can choose their own balance between feature resolution and invalid data rejection. The SmartScan glove is tested on a foot model and is shown to be robust against motion artifacts, having a mean accuracy of 2.9 mm (compared to a 3D model generated from optical imaging) without calibration.

Noise Removal Algorithm for Out-of-focus Blurred Images Based on Bilateral Filtering

The feature resolution of traditional methods for fuzzy image denoising is low, for the sake of improve the strepitus removal and investigation ability of defocused blurred night images, a strepitus removal algorithm based on bilateral filtering is suggested. The method include the following steps of: Building an out-of-focus blurred night scene image acquisition model with grid block feature matching of the out-of-focus blurred night scene image; Carrying out information enhancement processing of the out-of-focus blurred night scene image by adopting a high-resolution image detail feature enhancement technology; Collecting edge contour feature quantity of the out-of-focus blurred night scene image; Carrying out grid block feature matching design of the out-of-focus blurred night scene image by adopting a bilateral filtering information reconstruction technology; And building the gray-level histogram information location model of the out-of-focus blurred night scene image. Fuzzy pixel information fusion investigation method is used to collect gray features of defocused blurred night images. According to the feature collection results, bilateral filtering algorithm is used to automatically optimize the strepitus removal of defocused blurred night images. The simulation results show that the out-of-focus blurred night scene image using this method for machine learning has better strepitus removal performance, shorter time cost and higher export peak signal-to-strepitus proportion.

A Position Sensing Glove to Aid Ankle-Foot Orthosis Diagnosis and Treatment

A position sensing glove, called SmartScan, that creates a 3D virtual model of a real object is presented. The data from the glove is processed by a volume minimization algorithm to validate the position sensor data. This allows only data from the object’s surface to be retained. The data validation algorithm allows the user to progressively improve an image by repeatedly moving their hand over the object. In addition, the user can choose their own balance between feature resolution and invalid data rejection. The SmartScan glove is tested on a foot model and is shown to be robust against motion artifacts, and has a mean accuracy of 2.9 mm (compared to a 3D model generated from optical imaging) without calibration.

Coherence between Decomposed Components of Wrist and Finger PPG Signals by Imputing Missing Features and Resolving Ambiguous Features

Background: Feature extraction from photoplethysmography (PPG) signals is an essential step to analyze vascular and hemodynamic information. Different morphologies of PPG waveforms from different measurement sites appear. Various phenomena of missing or ambiguous features exist, which limit subsequent signal processing. Methods: The reasons that cause missing or ambiguous features of finger and wrist PPG pulses are analyzed based on the concept of component waves from pulse decomposition. Then, a systematic approach for missing-feature imputation and ambiguous-feature resolution is proposed. Results: From the experimental results, with the imputation and ambiguity resolution technique, features from 35,036 (98.7%) of 35,502 finger PPG cycles and 36307 (99.1%) of 36,652 wrist PPG cycles can be successfully identified. The extracted features became more stable and the standard deviations of their distributions were reduced. Furthermore, significant correlations up to 0.92 were shown between the finger and wrist PPG waveforms regarding the positions and widths of the third to fifth component waves. Conclusion: The proposed missing-feature imputation and ambiguous-feature resolution solve the problems encountered during PPG feature extraction and expand the feature availability for further processing. More intrinsic properties of finger and wrist PPG are revealed. The coherence between the finger and wrist PPG waveforms enhances the applicability of the wrist PPG.

AresB-Net: accurate residual binarized neural networks using shortcut concatenation and shuffled grouped convolution

This article proposes a novel network model to achieve better accurate residual binarized convolutional neural networks (CNNs), denoted as AresB-Net. Even though residual CNNs enhance the classification accuracy of binarized neural networks with increasing feature resolution, the degraded classification accuracy is still the primary concern compared with real-valued residual CNNs. AresB-Net consists of novel basic blocks to amortize the severe error from the binarization, suggesting a well-balanced pyramid structure without downsampling convolution. In each basic block, the shortcut is added to the convolution output and then concatenated, and then the expanded channels are shuffled for the next grouped convolution. In the downsampling when stride >1, our model adopts only the max-pooling layer for generating low-cost shortcut. This structure facilitates the feature reuse from the previous layers, thus alleviating the error from the binarized convolution and increasing the classification accuracy with reduced computational costs and small weight storage requirements. Despite low hardware costs from the binarized computations, the proposed model achieves remarkable classification accuracies on the CIFAR and ImageNet datasets.

Quantifying and correcting residual azimuthal anisotropic moveout in image gathers using dynamic time warping

We have developed a novel application of dynamic time warping (DTW) for correcting residual moveout in image gathers, enhancing seismic images, and determining azimuthal anisotropic orientation and relative intensity when moveout is caused by wave propagation through a medium possessing elliptical horizontally transverse isotropy (HTI). The method functions by first using DTW to determine the sequences of integer shifts that most closely match seismic traces within an image gather to its stack and then applying those shifts to flatten the gather. Flattening shifts are fitted to an ellipse to provide an approximation for the orientation and relative strength of elliptical HTI anisotropy. We evaluated the method on synthetic and 3D field data examples to show how it is able to (1) correct for residual azimuthal anisotropic moveout, (2) accurately recover high-frequency information and improve feature resolution in seismic images, and (3) determine the anisotropic orientation while providing a measure of relative strength of elliptic anisotropy. Although the method is not intended to replace anisotropic processing techniques for moveout correction, we find that it has the ability to inexpensively approximate the effects of such operations while providing a representation of the elliptic HTI anisotropy present within a volume.