Machine Learning Prediction of Antimicrobial Peptides

Abstract

Antibiotic resistance constitutes a global threat and could lead to a future pandemic. One strategy is to develop a new generation of antimicrobials. Naturally occurring antimicrobial peptides (AMPs) are recognized templates and some are already in clinical use. To accelerate the discovery of new antibiotics, it is useful to predict novel AMPs from the sequenced genomes of various organisms. The antimicrobial peptide database (APD) provided the first empirical peptide prediction program. It also facilitated the testing of the first machine-learning algorithms. This chapter provides an overview of machine-learning predictions of AMPs. Most of the predictors, such as AntiBP, CAMP, and iAMPpred, involve a single-label prediction of antimicrobial activity. This type of prediction has been expanded to antifungal, antiviral, antibiofilm, anti-TB, hemolytic, and anti-inflammatory peptides. The multiple functional roles of AMPs annotated in the APD also enabled multi-label predictions (iAMP-2L, MLAMP, and AMAP), which include antibacterial, antiviral, antifungal, antiparasitic, antibiofilm, anticancer, anti-HIV, antimalarial, insecticidal, antioxidant, chemotactic, spermicidal activities, and protease inhibiting activities. Also considered in predictions are peptide posttranslational modification, 3D structure, and microbial species-specific information. We compare important amino acids of AMPs implied from machine learning with the frequently occurring residues of the major classes of natural peptides. Finally, we discuss advances, limitations, and future directions of machine-learning predictions of antimicrobial peptides. Ultimately, we may assemble a pipeline of such predictions beyond antimicrobial activity to accelerate the discovery of novel AMP-based antimicrobials.

Keywords: Antimicrobial peptides; Database; Machine learning; Multidrug resistance; Peptide prediction.

Fig. 1.

Important amino acids derived from amino acid composition profiles of classic classes of antimicrobial peptides [3]: (A) α-helical and β-sheet families and (B) amino acid-rich families, including Trp-rich, His-rich, Pro-rich, and Leu-rich AMPs. Data obtained in the APD [13] in Dec 2020.

Fig. 2.

Information-content based five methods for prediction of antimicrobial peptides [20].

Fig. 3:

Percent hemolysis results with different amounts of LL-37 peptide against human red blood cells. The data from Table 11 were plotted. The best-fit line is y=0.2142x + 8.0017. The shaded grey area represents a 95% confidence interval.