Targeting Epigenetic Regulators Using Machine Learning: Potential Sirtuin 2 Inhibitors

2021 ◽  
Vol 20 (08) ◽  
pp. 841-851
Author(s):  
Andrew Kessler ◽  
Valentina L. Kouznetsova ◽  
Igor F. Tsigelny

Sirtuin 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that has been identified as a target for many diseases, including Parkinson’s disease (PD) and leukemia. Using 234 SIRT2 inhibitors from the ZINC15 database, we generated molecular descriptors with PaDEL and constructed a machine-learning (ML) model for the binary classification of SIRT2 inhibitors. To predict compounds with novel inhibitory mechanisms, we then applied the model on the ZINC15/FDA subset, yielding 107 potential SIRT2 inhibitors. For validation of these substances, we employed the binding analysis software AutoDock Vina to perform virtual screening, with which 43 compounds were considered best inhibitors at the [Formula: see text][Formula: see text]kcal/mol binding affinity threshold. Our results demonstrate the potential of ligand-based (LB) ML techniques in conjunction with receptor-based virtual screening (RBVS) to facilitate the drug discovery or repurposing.

Sensors ◽  
2021 ◽  
Vol 21 (21) ◽  
pp. 7417
Author(s):  
Alex J. Hope ◽  
Utkarsh Vashisth ◽  
Matthew J. Parker ◽  
Andreas B. Ralston ◽  
Joshua M. Roper ◽  
...  

Concussion injuries remain a significant public health challenge. A significant unmet clinical need remains for tools that allow related physiological impairments and longer-term health risks to be identified earlier, better quantified, and more easily monitored over time. We address this challenge by combining a head-mounted wearable inertial motion unit (IMU)-based physiological vibration acceleration (“phybrata”) sensor and several candidate machine learning (ML) models. The performance of this solution is assessed for both binary classification of concussion patients and multiclass predictions of specific concussion-related neurophysiological impairments. Results are compared with previously reported approaches to ML-based concussion diagnostics. Using phybrata data from a previously reported concussion study population, four different machine learning models (Support Vector Machine, Random Forest Classifier, Extreme Gradient Boost, and Convolutional Neural Network) are first investigated for binary classification of the test population as healthy vs. concussion (Use Case 1). Results are compared for two different data preprocessing pipelines, Time-Series Averaging (TSA) and Non-Time-Series Feature Extraction (NTS). Next, the three best-performing NTS models are compared in terms of their multiclass prediction performance for specific concussion-related impairments: vestibular, neurological, both (Use Case 2). For Use Case 1, the NTS model approach outperformed the TSA approach, with the two best algorithms achieving an F1 score of 0.94. For Use Case 2, the NTS Random Forest model achieved the best performance in the testing set, with an F1 score of 0.90, and identified a wider range of relevant phybrata signal features that contributed to impairment classification compared with manual feature inspection and statistical data analysis. The overall classification performance achieved in the present work exceeds previously reported approaches to ML-based concussion diagnostics using other data sources and ML models. This study also demonstrates the first combination of a wearable IMU-based sensor and ML model that enables both binary classification of concussion patients and multiclass predictions of specific concussion-related neurophysiological impairments.


IEEE Access ◽  
2019 ◽  
Vol 7 ◽  
pp. 135703-135719
Author(s):  
Weijun Zhu ◽  
Huanmei Wu ◽  
Miaolei Deng

Author(s):  
Alexander M. Zolotarev ◽  
Brian J. Hansen ◽  
Ekaterina A. Ivanova ◽  
Katelynn M. Helfrich ◽  
Ning Li ◽  
...  

Background: Atrial fibrillation (AF) can be maintained by localized intramural reentrant drivers. However, AF driver detection by clinical surface-only multielectrode mapping (MEM) has relied on subjective interpretation of activation maps. We hypothesized that application of machine learning to electrogram frequency spectra may accurately automate driver detection by MEM and add some objectivity to the interpretation of MEM findings. Methods: Temporally and spatially stable single AF drivers were mapped simultaneously in explanted human atria (n=11) by subsurface near-infrared optical mapping (NIOM; 0.3 mm 2 resolution) and 64-electrode MEM (higher density or lower density with 3 and 9 mm 2 resolution, respectively). Unipolar MEM and NIOM recordings were processed by Fourier transform analysis into 28 407 total Fourier spectra. Thirty-five features for machine learning were extracted from each Fourier spectrum. Results: Targeted driver ablation and NIOM activation maps efficiently defined the center and periphery of AF driver preferential tracks and provided validated annotations for driver versus nondriver electrodes in MEM arrays. Compared with analysis of single electrogram frequency features, averaging the features from each of the 8 neighboring electrodes, significantly improved classification of AF driver electrograms. The classification metrics increased when less strict annotation, including driver periphery electrodes, were added to driver center annotation. Notably, f1-score for the binary classification of higher-density catheter data set was significantly higher than that of lower-density catheter (0.81±0.02 versus 0.66±0.04, P <0.05). The trained algorithm correctly highlighted 86% of driver regions with higher density but only 80% with lower-density MEM arrays (81% for lower-density+higher-density arrays together). Conclusions: The machine learning model pretrained on Fourier spectrum features allows efficient classification of electrograms recordings as AF driver or nondriver compared with the NIOM gold-standard. Future application of NIOM-validated machine learning approach may improve the accuracy of AF driver detection for targeted ablation treatment in patients.


Author(s):  
Z. Neili ◽  
M. Fezari ◽  
A. Redjati

The acquisition of Breath sounds (BS) signals from a human respiratory system with an electronic stethoscope, provide and offer prominent information which helps the doctors to diagnosis and classification of pulmonary diseases. Unfortunately, this BS signals with other biological signals have a non-stationary nature according to the variation of the lung volume, and this nature makes it difficult to analyze and classify between several diseases. In this study, we were focused on comparing the ability of the extreme learning machine (ELM) and k-nearest neighbour (K-nn) machine learning algorithms in the classification of adventitious and normal breath sounds. To do so, the empirical mode decomposition (EMD) was used in this work to analyze BS, this method is rarely used in the breath sounds analysis. After the EMD decomposition of the signals into Intrinsic Mode Functions (IMFs), the Hjorth descriptors (Activity) and Permutation Entropy (PE) features were extracted from each IMFs and combined for classification stage. The study has found that the combination of features (activity and PE) yielded an accuracy of 90.71%, 95% using ELM and K-nn respectively in binary classification (normal and abnormal breath sounds), and 83.57%, 86.42% in multiclass classification (five classes).


Sensors ◽  
2021 ◽  
Vol 21 (17) ◽  
pp. 5896
Author(s):  
Eddi Miller ◽  
Vladyslav Borysenko ◽  
Moritz Heusinger ◽  
Niklas Niedner ◽  
Bastian Engelmann ◽  
...  

Changeover times are an important element when evaluating the Overall Equipment Effectiveness (OEE) of a production machine. The article presents a machine learning (ML) approach that is based on an external sensor setup to automatically detect changeovers in a shopfloor environment. The door statuses, coolant flow, power consumption, and operator indoor GPS data of a milling machine were used in the ML approach. As ML methods, Decision Trees, Support Vector Machines, (Balanced) Random Forest algorithms, and Neural Networks were chosen, and their performance was compared. The best results were achieved with the Random Forest ML model (97% F1 score, 99.72% AUC score). It was also carried out that model performance is optimal when only a binary classification of a changeover phase and a production phase is considered and less subphases of the changeover process are applied.


2019 ◽  
Vol 2 ◽  
pp. 1-8
Author(s):  
Lukas Gokl ◽  
Marvin Mc Cutchan ◽  
Bartosz Mazurkiewicz ◽  
Paolo Fogliaroni ◽  
Ioannis Giannopoulos

Abstract. Location Based Services (LBS) are definitely very helpful for people that interact within an unfamiliar environment, but also for those that already possess a certain level of familiarity with it. In order to avoid overwhelming familiar users with unnecessary information, the level of details offered by the LBS shall be adapted to the level of familiarity with the environment: providing more details to unfamiliar users and a lighter amount of information (that would be superfluous, if not even misleading) to the users that are more familiar with the current environment. Currently, the information exchange between the service and its users is not taking into account familiarity. Within this work, we investigate the potential of machine learning for a binary classification of environment familiarity (i.e., familiar vs unfamiliar) with the surrounding environment. For this purpose, a 3D virtual environment based on a part of Vienna, Austria was designed using datasets from the municipal government. During a navigation experiment with 22 participants we collected ground truth data in order to train four machine learning algorithms. The captured data included motion and orientation of the users as well as visual interaction with the surrounding buildings during navigation. This work demonstrates the potential of machine learning for predicting the state of familiarity as an enabling step for the implementation of LBS better tailored to the user.


2021 ◽  
Author(s):  
ANKIT GHOSH ◽  
ALOK KOLE

<p>The improvement of Artificial Intelligence (AI) and Machine Learning (ML) can help radiologists in tumor diagnostics without invasive measures. Magnetic resonance imaging (MRI) is a very useful method for diagnosis of tumors in human brain. In this paper, brain MRI images have been analyzed to detect the regions containing tumors and classify these regions into three different tumor categories: meningioma, glioma, and pituitary. This paper presents the implementation and comparison of various enhanced ML algorithms for the detection and classification of brain tumors. A brain tumor is the growth of abnormal cells in the human brain. Brain tumors can be cancerous or non-cancerous. Cancerous or malignant brain tumors can be life threatening. Hence, detection and classification of brain tumors at an early stage is extremely important. In this paper, enhanced ML algorithms have been implemented to predict the presence or the absence of brain tumors using binary classification and to predict whether a patient has brain tumor or not and if he does, detect the type of brain tumor using multi-class classification. The dataset that has been used to perform the binary classification task comprises of two types of brain MRI images with tumor and without tumor. Here nine ML algorithms namely, Support Vector Machine (SVM), Logistic Regression, K-Nearest Neighbor (KNN), Naïve Bayes (NB), Decision Tree (DT) classifier, Random Forest classifier, XGBoost classifier, Stochastic Gradient Descent (SGD) classifier and Gradient Boosting classifier have been used to classify the MRI images. A comparative analysis of the ML algorithms has been performed based on a few performance metrics such as accuracy, recall, and precision, F1-score, AUC-ROC curve and AUC-PR curve. Gradient Boosting classifier has outperformed all the other algorithms with an accuracy of 92.4%, recall of 94.4%, precision of 85%, F1-score of 89.5%, AUC-ROC of 97.2% and an AUC-PR of 91.4%. To address the multi-class classification problem, four ML algorithms namely, SVM, KNN, Random Forest classifier and XGBoost classifier have been employed. In this case, the dataset that has been used consists of four types of brain MRI images with glioma tumor, meningioma tumor, and pituitary tumor and with no tumor. The performances of the ML algorithms have been compared based on accuracy, recall, precision and the F1-score. XGBoost classifier has surpassed all the other algorithms in terms of accuracy, precision, recall and F1-score. XGBoost has produced an accuracy of 90%, precision of 90%, and recall of 90% and F1-score of 90%.</p>


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