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Creators/Authors contains: "Hamid, Md Nafiz"

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  1. Abstract Motivation

    Antibiotic resistance constitutes a major public health crisis, and finding new sources of antimicrobial drugs is crucial to solving it. Bacteriocins, which are bacterially produced antimicrobial peptide products, are candidates for broadening the available choices of antimicrobials. However, the discovery of new bacteriocins by genomic mining is hampered by their sequences’ low complexity and high variance, which frustrates sequence similarity-based searches.

    Results

    Here we use word embeddings of protein sequences to represent bacteriocins, and apply a word embedding method that accounts for amino acid order in protein sequences, to predict novel bacteriocins from protein sequences without using sequence similarity. Our method predicts, with a high probability, six yet unknown putative bacteriocins in Lactobacillus. Generalized, the representation of sequences with word embeddings preserving sequence order information can be applied to peptide and protein classification problems for which sequence similarity cannot be used.

    Availability and implementation

    Data and source code for this project are freely available at: https://github.com/nafizh/NeuBI.

    Supplementary information

    Supplementary data are available at Bioinformatics online.

     
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  2. Abstract

    Bacteriocins, the ribosomally produced antimicrobial peptides of bacteria, represent an untapped source of promising antibiotic alternatives. However, bacteriocins display diverse mechanisms of action, a narrow spectrum of activity, and inherent challenges in natural product isolation making in vitro verification of putative bacteriocins difficult. A subset of bacteriocins exert their antimicrobial effects through favorable biophysical interactions with the bacterial membrane mediated by the charge, hydrophobicity, and conformation of the peptide. We have developed a pipeline for bacteriocin‐derived compound design and testing that combines sequence‐free prediction of bacteriocins using machine learning and a simple biophysical trait filter to generate 20 amino acid peptides that can be synthesized and evaluated for activity. We generated 28,895 total 20‐mer candidate peptides and scored them for charge, α‐helicity, and hydrophobic moment. Of those, we selected 16 sequences for synthesis and evaluated their antimicrobial, cytotoxicity, and hemolytic activities. Peptides with the overall highest scores for our biophysical parameters exhibited significant antimicrobial activity againstEscherichia coliandPseudomonas aeruginosa. Our combined method incorporates machine learning and biophysical‐based minimal region determination to create an original approach to swiftly discover bacteriocin candidates amenable to rapid synthesis and evaluation for therapeutic use.

     
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