KEMP-PIP: A Feature-Fusion Based Approach for Pro-inflammatory Peptide Prediction

Pro-inflammatory peptides (PIPs) play critical roles in immune signaling and inflammation but are difficult to identify experimentally due to costly and time-consuming assays. To address this challenge, we present KEMP-PIP, a hybrid machine learning framework that integrates deep protein embeddings with handcrafted descriptors for robust PIP prediction. Our approach combines contextual embeddings from pretrained ESM protein language models with multi-scale k-mer frequencies, physicochemical descriptors, and modlAMP sequence features. Feature pruning and class-weighted logistic regression manage high dimensionality and class imbalance, while ensemble averaging with an optimized decision threshold enhances the sensitivity–specificity balance. Through systematic ablation studies, we demonstrate that integrating complementary feature sets consistently improves predictive performance. On the standard benchmark dataset, KEMP-PIP achieves an MCC of 0.505, accuracy of 0.752, and AUC of 0.762, outperforming ProIn-fuse, MultiFeatVotPIP, and StackPIP. Relative to StackPIP, these results represent improvements of 9.5% in MCC and 4.8% in both accuracy and AUC. The KEMP-PIP web server is freely available at https://nilsparrow1920-kemp-pip.hf.space/ and the full implementation at https://github.com/S18-Niloy/KEMP-PIP.