Post-translational modifications (PTMs) are fundamental to essential biological processes, exerting significant influence over gene expression, protein localization, stability, and genome replication. Sumoylation, a PTM involving the covalent addition of a chemical group to a specific protein sequence, profoundly impacts the functional diversity of proteins. Notably, identifying sumoylation sites has garnered significant attention due to their crucial roles in proteomic functions and their implications in various diseases, including Parkinson’s and Alzheimer’s. Despite the proposal of several computational models for identifying sumoylation sites, their effectiveness could be improved by the limitations associated with conventional learning methodologies. In this study, we introduce pseudo-position-specific scoring matrix (PsePSSM), a robust computational model designed for accurately predicting sumoylation sites using an optimized deep learning algorithm and efficient feature extraction techniques. Moreover, to streamline computational processes and eliminate irrelevant and noisy features, sequential forward selection using a support vector machine (SFS-SVM) is implemented to identify optimal features. The multi-layer Deep Neural Network (DNN) is a robust classifier, facilitating precise sumoylation site prediction. We meticulously assess the performance of PSSM-Sumo through a tenfold cross-validation approach, employing various statistical metrics such as the Matthews Correlation Coefficient (MCC), accuracy, sensitivity, specificity, and the Area under the ROC Curve (AUC). Comparative analyses reveal that PSSM-Sumo achieves an exceptional average prediction accuracy of 98.71%, surpassing existing models. The robustness and accuracy of the proposed model position it as a promising tool for advancing drug discovery and the diagnosis of diverse diseases linked to sumoylation sites.
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