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2000
Volume 25, Issue 2
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

Background

Epilepsy remains the most common and chronic disorder demanding long-term management. The impact of epilepsy disease is a cause of great concern and has resulted in efforts to develop treatment for epilepsy. It occurs due to an increase in neuronal excitability produced by changes affecting the voltage-dependent properties of Voltage-gated Sodium Channels (VGSCs).

Materials and Methods

Weka, a popular suite for machine learning techniques, was used on a dataset comprising 1781 chemical compounds, showing inhibition activity for sodium channel protein IX alpha subunit. After the analysis of the dataset obtained from ChEMBL, molecular fingerprints were computed for the molecules by the ChemDes server. Different classifiers available in the Weka software were explored to find out the algorithm that could be more suitable for the dataset or produce the highest accuracy for the classification of molecules as active or inactive.

Results

In this work, a comprehensive comparison of different classifiers in the Weka suite for the prediction of active, inactive, and intermediate classes of molecules showing inhibition against human NaV1.7 protein was made. The prediction accuracy of these classifiers was assessed based on performance measures, including accuracy, Root Mean Squared Error (RMSE), Receiver Operating Characteristic (ROC), precision, Mathews Correlation Coefficient (MCC), recall, and F-measure. The comparison of results for model performance demonstrated that the OneR classifier performed best over others when validated using percentage split, cross-validation, and supplied test methods. J48 and Bagging also performed equally well in the prediction of different classes with an MCC value of 1, ROC area equal to 1, and RMSE close to 0.

Conclusion

Machine Learning (ML) tools provide a fast, reliable, and cost-effective approach required to identify or predict inhibitory molecules for the treatment of a disease. This study shows that the ML methods, particularly OneR, J48, and Bagging have the ability to identify active and inactive classes of compounds for the human NaV1.7 protein target. Such predictive models may provide a reliable and time-saving approach that can aid in the design of potential inhibitors for the treatment of epilepsy disease.

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