Identifying antimicrobial peptides in genomes using machine learning

Legana Fingerhut used machine learning to improve predictions of antimicrobial peptides (AMPs) from protein sequences. Her associated framework was the first to specifically address the problem of identifying AMPs from whole-genome data. Her work leads to improved workflows for identifying novel AMPs which advances our understanding of the innate immune system

Advances in Antimicrobial Peptide Discovery via Machine Learning and Delivery via Nanotechnology

Antimicrobial peptides (AMPs) have been investigated for their potential use as an alternative to antibiotics due to the increased demand for new antimicrobial agents. AMPs, widely found in nature and obtained from microorganisms, have a broad range of antimicrobial protection, allowing them to be applied in the treatment of infections caused by various pathogenic microorganisms. Since these peptides are primarily cationic, they prefer anionic bacterial membranes due to electrostatic interactions. However, the applications of AMPs are currently limited owing to their hemolytic activity, poor bioavailability, degradation from proteolytic enzymes, and high-cost production. To overcome these limitations, nanotechnology has been used to improve AMP bioavailability, permeation across barriers, and/or protection against degradation. In addition, machine learning has been investigated due to its time-saving and cost-effective algorithms to predict AMPs. There are numerous databases available to train machine learning models. In this review, we focus on nanotechnology approaches for AMP delivery and advances in AMP design via machine learning. The AMP sources, classification, structures, antimicrobial mechanisms, their role in diseases, peptide engineering technologies, currently available databases, and machine learning techniques used to predict AMPs with minimal toxicity are discussed in detail

AMAP : Hierarchical multi-label prediction of biologically active and antimicrobial peptides

Due to increase in antibiotic resistance in recent years, development of efficient and accurate techniques for discovery and design of biologically active peptides such as antimicrobial peptides (AMPs) has become essential. The screening of natural and synthetic AMPs in the wet lab is a challenge due to time and cost involved in such experiments. Bioinformatics methods can be used to speed up discovery and design of antimicrobial peptides by limiting the wet-lab search to promising peptide sequences. However, most such tools are typically limited to the prediction of whether a peptide exhibits antimicrobial activity or not and they do not identify the exact type of the biological activities of these peptides. In this work, we have designed a machine learning based model called AMAP for predicting biological activity of peptides with a specialized focus on antimicrobial activity prediction. AMAP used multi-label classification to predict 14 different types of biological functions of a given peptide sequence with improved accuracy in comparison to existing state of the art techniques. We have performed stringent performance analyses of the proposed method. In addition to cross-validation and performance comparison with existing AMP predictors, AMAP has also been benchmarked on recently published experimentally verified peptides that were not a part of our training set. We have also analyzed features used in this work and our analysis shows that the proposed predictor can generalize well in predicting biological activity of novel peptide sequences. A webserver of the proposed method is available at the URL: http://faculty.pieas.edu.pk/fayyaz/software.html#AMA

Combining genetic algorithm with machine learning strategies for designing potent antimicrobial peptides

Background Current methods in machine learning provide approaches for solving challenging, multiple constraint design problems. While deep learning and related neural networking methods have state-of-the-art performance, their vulnerability in decision making processes leading to irrational outcomes is a major concern for their implementation. With the rising antibiotic resistance, antimicrobial peptides (AMPs) have increasingly gained attention as novel therapeutic agents. This challenging design problem requires peptides which meet the multiple constraints of limiting drug-resistance in bacteria, preventing secondary infections from imbalanced microbial flora, and avoiding immune system suppression. AMPs offer a promising, bioinspired design space to targeting antimicrobial activity, but their versatility also requires the curated selection from a combinatorial sequence space. This space is too large for brute-force methods or currently known rational design approaches outside of machine learning. While there has been progress in using the design space to more effectively target AMP activity, a widely applicable approach has been elusive. The lack of transparency in machine learning has limited the advancement of scientific knowledge of how AMPs are related among each other, and the lack of general applicability for fully rational approaches has limited a broader understanding of the design space. Methods Here we combined an evolutionary method with rough set theory, a transparent machine learning approach, for designing antimicrobial peptides (AMPs). Our method achieves the customization of AMPs using supervised learning boundaries. Our system employs in vitro bacterial assays to measure fitness, codon-representation of peptides to gain flexibility of sequence selection in DNA-space with a genetic algorithm and machine learning to further accelerate the process. Results We use supervised machine learning and a genetic algorithm to find a peptide active against S. epidermidis, a common bacterial strain for implant infections, with an improved aggregation propensity average for an improved ease of synthesis. Conclusions Our results demonstrate that AMP design can be customized to maintain activity and simplify production. To our knowledge, this is the first time when codon-based genetic algorithms combined with rough set theory methods is used for computational search on peptide sequences

Prediction of Novel Antibiofilm Peptides from Diverse Habitats using Machine Learning

Multidrug resistant bacteria often lead to biofilm formation. Biofilm is a colonizedform of pathogens (fungi, bacteria) attached to surfaces like animal or plant tissues, medical devices like catheters, and artificial heart valves. Biofilm formation prolongs the survival of microorganisms in an adaptive environment, leading to the spread of infection in different organs and causing a high morbidity rate. Given the rise of chronic infection and antibiotic resistance due to biofilm, it is essential to find an alternative solution to control biofilm infections. Antibiofilm peptides can interact with these biofilm-creating pathogens to inhibit growth, virulence, and biofilm formation. We hypothesized that mining the existing peptide databases from diverse habitats could provide potential antibiofilm activities for our work. We developed a computational model to predict the antibiofilm properties by applying machine learning algorithms like support vector machine, random forest, extreme gradient boosting, and multilayer perceptron classifier. We evaluated more than 240 antibiofilm peptides and more than 570 different compositions and motif-based features to build our prediction model. We also created a regression model on top of our classifier to predict the effectiveness of peptides by curating minimum inhibitory concentration against biofilm. Our classifiers achieved greater than 98% accuracy while the harmonic mean of precision-recall (F1) and Matthews correlation coefficient (MCC) scores obtained are greater than 0.91. Using this two-tier model approach, we assessed more extensive databases of antimicrobial, anticancer, antiviral, and dairy peptides for potential antibiofilm functionality and came up with the top ten potential candidates of antibiofilm peptides

A bioinformatic study of antimicrobial peptides identified in the Black Soldier Fly (BSF) Hermetia illucens (Diptera: Stratiomyidae)

Antimicrobial peptides (AMPs) play a key role in the innate immunity, the first line of defense against bacteria, fungi, and viruses. AMPs are small molecules, ranging from 10 to 100 amino acid residues produced by all living organisms. Because of their wide biodiversity, insects are among the richest and most innovative sources for AMPs. In particular, the insect Hermetia illucens (Diptera: Stratiomyidae) shows an extraordinary ability to live in hostile environments, as it feeds on decaying substrates, which are rich in microbial colonies, and is one of the most promising sources for AMPs. The larvae and the combined adult male and female H. illucens transcriptomes were examined, and all the sequences, putatively encoding AMPs, were analysed with different machine learning-algorithms, such as the Support Vector Machine, the Discriminant Analysis, the Artificial Neural Network, and the Random Forest available on the CAMP database, in order to predict their antimicrobial activity. Moreover, the iACP tool, the AVPpred, and the Antifp servers were used to predict the anticancer, the antiviral, and the antifungal activities, respectively. The related physicochemical properties were evaluated with the Antimicrobial Peptide Database Calculator and Predictor. These analyses allowed to identify 57 putatively active peptides suitable for subsequent experimental validation studies