Antimicrobial peptide identification using multi-scale convolutional network

Background: Antibiotic resistance has become an increasingly serious problem in the past decades. As an alternative choice, antimicrobial peptides (AMPs) have attracted lots of attention. To identify new AMPs, machine learning methods have been commonly used. More recently, some deep learning methods have also been applied to this problem. Results: In this paper, we designed a deep learning model to identify AMP sequences. We employed the embedding layer and the multi-scale convolutional network in our model. The multi-scale convolutional network, which contains multiple convolutional layers of varying filter lengths, could utilize all latent features captured by the multiple convolutional layers. To further improve the performance, we also incorporated additional information into the designed model and proposed a fusion model. Results showed that our model outperforms the state-of-the-art models on two AMP datasets and the Antimicrobial Peptide Database (APD)3 benchmark dataset. The fusion model also outperforms the state-of-the-art model on an anti-inflammatory peptides (AIPs) dataset at the accuracy. Conclusions: Multi-scale convolutional network is a novel addition to existing deep neural network (DNN) models. The proposed DNN model and the modified fusion model outperform the state-of-the-art models for new AMP discovery. The source code and data are available at https://github.com/zhanglabNKU/APIN

Antimicrobial peptide identification using multi-scale convolutional network

Background: Antibiotic resistance has become an increasingly serious problem in the past decades. As an alternative choice, antimicrobial peptides (AMPs) have attracted lots of attention. To identify new AMPs, machine learning methods have been commonly used. More recently, some deep learning methods have also been applied to this problem. Results: In this paper, we designed a deep learning model to identify AMP sequences. We employed the embedding layer and the multi-scale convolutional network in our model. The multi-scale convolutional network, which contains multiple convolutional layers of varying filter lengths, could utilize all latent features captured by the multiple convolutional layers. To further improve the performance, we also incorporated additional information into the designed model and proposed a fusion model. Results showed that our model outperforms the state-of-the-art models on two AMP datasets and the Antimicrobial Peptide Database (APD)3 benchmark dataset. The fusion model also outperforms the state-of-the-art model on an anti-inflammatory peptides (AIPs) dataset at the accuracy. Conclusions: Multi-scale convolutional network is a novel addition to existing deep neural network (DNN) models. The proposed DNN model and the modified fusion model outperform the state-of-the-art models for new AMP discovery. The source code and data are available at https://github.com/zhanglabNKU/APIN

Bioactive Molecules from the Innate Immunity of Ascidians and Innovative Methods of Drug Discovery: A Computational Approach Based on Artificial Intelligence

The study of bioactive molecules of marine origin has created an important bridge between biological knowledge and its applications in biotechnology and biomedicine. Current studies in different research fields, such as biomedicine, aim to discover marine molecules characterized by biological activities that can be used to produce potential drugs for human use. In recent decades, increasing attention has been paid to a particular group of marine invertebrates, the Ascidians, as they are a source of bioactive products. We describe omics data and computational methods relevant to identifying the mechanisms and processes of innate immunity underlying the biosynthesis of bioactive molecules, focusing on innovative computational approaches based on Artificial Intelligence. Since there is increasing attention on finding new solutions for a sustainable supply of bioactive compounds, we propose that a possible improvement in the biodiscovery pipeline might also come from the study and utilization of marine invertebrates’ innate immunity

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

pLMFPPred: a novel approach for accurate prediction of functional peptides integrating embedding from pre-trained protein language model and imbalanced learning

Functional peptides have the potential to treat a variety of diseases. Their good therapeutic efficacy and low toxicity make them ideal therapeutic agents. Artificial intelligence-based computational strategies can help quickly identify new functional peptides from collections of protein sequences and discover their different functions.Using protein language model-based embeddings (ESM-2), we developed a tool called pLMFPPred (Protein Language Model-based Functional Peptide Predictor) for predicting functional peptides and identifying toxic peptides. We also introduced SMOTE-TOMEK data synthesis sampling and Shapley value-based feature selection techniques to relieve data imbalance issues and reduce computational costs. On a validated independent test set, pLMFPPred achieved accuracy, Area under the curve - Receiver Operating Characteristics, and F1-Score values of 0.974, 0.99, and 0.974, respectively. Comparative experiments show that pLMFPPred outperforms current methods for predicting functional peptides.The experimental results suggest that the proposed method (pLMFPPred) can provide better performance in terms of Accuracy, Area under the curve - Receiver Operating Characteristics, and F1-Score than existing methods. pLMFPPred has achieved good performance in predicting functional peptides and represents a new computational method for predicting functional peptides.Comment: 20 pages, 5 figures,under revie

Artificial intelligence-driven antimicrobial peptide discovery

Antimicrobial peptides (AMPs) emerge as promising agents against antimicrobial resistance, providing an alternative to conventional antibiotics. Artificial intelligence (AI) revolutionized AMP discovery through both discrimination and generation approaches. The discriminators aid the identification of promising candidates by predicting key peptide properties such as activity and toxicity, while the generators learn the distribution over peptides and enable sampling novel AMP candidates, either de novo, or as analogues of a prototype peptide. Moreover, the controlled generation of AMPs with desired properties is achieved by discriminator-guided filtering, positive-only learning, latent space sampling, as well as conditional and optimized generation. Here we review recent achievements in AI-driven AMP discovery, highlighting the most exciting directions

Role of artificial intelligence in fighting antimicrobial resistance in pediatrics

Artificial intelligence (AI) is a field of science and engineering concerned with the computational understanding of what is commonly called intelligent behavior. AI is extremely useful in many human activities including medicine. The aim of our narrative review is to show the potential role of AI in fighting antimicrobial resistance in pediatric patients. We searched for PubMed articles published from April 2010 to April 2020 containing the keywords “artificial intelligence”, “machine learning”, “antimicrobial resistance”, “antimicrobial stewardship”, “pediatric”, and “children”, and we described the different strategies for the application of AI in these fields. Literature analysis showed that the applications of AI in health care are potentially endless, contributing to a reduction in the development time of new antimicrobial agents, greater diagnostic and therapeutic appropriateness, and, simultaneously, a reduction in costs. Most of the proposed AI solutions for medicine are not intended to replace the doctor’s opinion or expertise, but to provide a useful tool for easing their work. Considering pediatric infectious diseases, AI could play a primary role in fighting antibiotic resistance. In the pediatric field, a greater willingness to invest in this field could help antimicrobial stewardship reach levels of effectiveness that were unthinkable a few years ago

Accelerating Antimicrobial Peptide Discovery with Latent Structure

Antimicrobial peptides (AMPs) are promising therapeutic approaches against drug-resistant pathogens. Recently, deep generative models are used to discover new AMPs. However, previous studies mainly focus on peptide sequence attributes and do not consider crucial structure information. In this paper, we propose a latent sequence-structure model for designing AMPs (LSSAMP). LSSAMP exploits multi-scale vector quantization in the latent space to represent secondary structures (e.g. alpha helix and beta sheet). By sampling in the latent space, LSSAMP can simultaneously generate peptides with ideal sequence attributes and secondary structures. Experimental results show that the peptides generated by LSSAMP have a high probability of antimicrobial activity. Our wet laboratory experiments verified that two of the 21 candidates exhibit strong antimicrobial activity. The code is released at https://github.com/dqwang122/LSSAMP.Comment: KDD 202