The exponential growth of genomic and proteomic data has made computational protein–protein interaction (PPI) prediction indispensable, driving the need for a comprehensive and method-aware evaluation of supervised learning approaches. PPIs are fundamental to understanding cellular processes and disease mechanisms, yet experimental identification remains slow, costly, and difficult to scale. This survey systematically investigates ten supervised learning models—Extreme Learning Machine (ELM), Convolutional Neural Networks (CNNs), Graph Neural Networks (GNNs), Deep Neural Networks (DNNs), Naïve Bayes, Probabilistic Decision Tree, Support Vector Machine (SVM), Least Squares SVM (LS-SVM), K-Nearest Neighbor (KNN), and Weighted K-Nearest Neighbor (WKNN)—through a tri-layered framework that integrates
Comparative Quantitative Analysis, Comparative Observational Analysis,
and Experimental Evaluations. Beyond conventional accuracy summaries, this work provides
critical commentary tied to real-world use, analyzing where techniques succeed or fail in practice—for instance, when instance-based methods bottleneck during inference, when kernel choices influence SVM variance, or when deep architectures trade accuracy for computational cost. The survey also offers concrete deployment guidance, such as calibration insights for WKNN versus KNN under varying feature noise or dataset curation quality, delivering operational perspectives that typical surveys omit. Comparative Quantitative Analysis consolidates metrics such as accuracy, F1-score, and computational time from the existing literature, while Comparative Observational Analysis evaluates interpretability, scalability, dataset suitability, and efficiency. Complementing these,
Experimental Evaluations conducted by the authors empirically validate model performance on benchmark datasets. Together, these layers provide a unified and evidence-backed perspective on algorithmic strengths, weaknesses, and practical applicability. Findings show that GNNs and DNNs achieve the highest predictive accuracy due to their ability to capture structural and topological relationships, whereas ELM and Naïve Bayes offer superior efficiency. SVM and LS-SVM maintain robust stability under noisy conditions, and CNNs are well-suited for sequence-based prediction tasks. By combining empirical validation, critical insights, and deployment-focused recommendations, this survey delivers decision-grade guidance that bridges theoretical understanding with real-world implementation, thus clarifying the trade-offs among accuracy, efficiency, and scalability in PPI detection research.
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