Prediction of Chemically Modified Antimicrobial Peptides and Their Sub-functional Activities Using Hybrid Features

Antimicrobial peptides (AMPs) demonstrate a broad spectrum of activities against various pathogens, thereby offering a promising strategy to mitigate the urgent challenge of antimicrobial resistance. Recent studies indicate that chemically modified AMPs (cmAMPs), which contain chemically modified amino acids, have the potential to alleviate the adverse effects commonly associated with conventional AMPs. Nevertheless, there remains a notable deficiency in computational methods specifically designed for the analysis and prediction of cmAMPs and their sub-function predictions. In this study, we proposed a two-layer model, termed as iCMAMP, aimed for the identification of cmAMPs and their sub-functional activities. The first layer, referred to as iCMAMP-1L, integrates three categories encompassing seven distinct groups of features, in conjunction with an ensemble method designed at enhancing predictive accuracy for cmAMPs. This ensemble approach effectively extracts relevant insights from a heterogeneous array of features sets while addressing potential dimensionality challenges. On the test dataset, iCMAMP-1L achieved an ACC of 0.934 and an MCC of 0.868, representing improvements of 3.4% and 6.8%, respectively, over AntiMPmod, which is the sole existing method for predicting cmAMPs. A comparative analysis between cmAMPs and their corresponding AMPs revealed that chemical modifications can significantly reduce hemolysis and toxicity associated with AMPs, while the functional characteristics of the peptides are primarily determined by their sequences. The second layer of our model, designated as iCMAMP-2L, employed a multi-label classification approach to predict the sub-functional activities of cmAMPs, with a specific focus on the dipeptide composition-based features. On the test dataset, iCMAMP-2L achieved an Accuracy of 0.390 and an Absolute true of 0.621. The data and Python code used in the iCMAMP model are available at https://github.com/swicher123/iCMAMP/tree/master .