HyperACP: A cutting-edge hybrid framework for anticancer peptide classification via scalable feature extraction and adaptive neighbor-based synthesis

Cancer remains a major contributor to global mortality, constituting a significant and escalating threat to human health. Anticancer peptides (ACPs) have emerged as promising therapeutic agents due to their specific mechanisms of action, pronounced tumor-targeting capability, and low toxicity. Nevertheless, traditional approaches for ACP identification are constrained by their reliance on shallow, hand-crafted sequence features, which fail to capture deeper semantic and structural characteristics. Moreover, such models exhibit limited robustness and interpretability when confronted with practical challenges such as severe class imbalance. To address these limitations, this study proposes HyperACP, an innovative framework for ACP recognition that integrates deep representation learning, adaptive sampling, and mechanistic interpretability. The framework leverages the ESMC protein language model to extract comprehensive sequence features and employs a novel adaptive algorithm, ANBS, to mitigate class imbalance at the decision boundary. For enhanced model transparency, SHAP-Res is incorporated to elucidate the contributions of individual residues to the final predictions. Comprehensive evaluations demonstrate that HyperACP consistently outperforms state-of-the-art methods across multiple datasets and validation protocols—including 10-fold cross-validation and independent test sets—according to metrics such as Accuracy (ACC), Sensitivity (SN), Specificity (SP), Matthews Correlation Coefficient (MCC), and Area Under the Curve (AUC). Furthermore, the model yields biologically interpretable results, pinpointing key residues (K, L, F, G) known to play pivotal roles in anticancer activity. These findings provide not only a robust predictive tool (available at www.hyperacp.com) but also novel insights into the structure-function relationships underlying ACPs.