AMPlify: attentive deep learning model for discovery of novel antimicrobial peptides effective against WHO priority pathogens

被引:110
作者
Li, Chenkai [1 ,2 ]
Sutherland, Darcy [1 ,3 ,4 ]
Hammond, S. Austin [1 ]
Yang, Chen [1 ,2 ]
Taho, Figali [1 ,2 ]
Bergman, Lauren [5 ]
Houston, Simon [5 ]
Warren, Rene L. [1 ]
Wong, Titus [4 ,6 ]
Hoang, Linda M. N. [3 ,4 ]
Cameron, Caroline E. [5 ,7 ]
Helbing, Caren C. [5 ]
Birol, Inanc [1 ,3 ,4 ,8 ]
机构
[1] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada
[2] Univ British Columbia, Bioinformat Grad Program, Vancouver, BC V6T 1Z4, Canada
[3] British Columbia Ctr Dis Control, Publ Hlth Lab, Vancouver, BC V5Z 4R4, Canada
[4] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 1Z4, Canada
[5] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8P 5C3, Canada
[6] Vancouver Gen Hosp, Med Microbiol Lab, Vancouver, BC V5Z 1M9, Canada
[7] Univ Washington, Dept Med, Div Infect Dis, Seattle, WA 98195 USA
[8] Univ British Columbia, Dept Med Genet, Vancouver, BC V6H 3N1, Canada
基金
美国国家卫生研究院;
关键词
Antimicrobial peptide; Deep learning; Attention mechanism; PREDICTION; RESISTANCE;
D O I
10.1186/s12864-022-08310-4
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background Antibiotic resistance is a growing global health concern prompting researchers to seek alternatives to conventional antibiotics. Antimicrobial peptides (AMPs) are attracting attention again as therapeutic agents with promising utility in this domain, and using in silico methods to discover novel AMPs is a strategy that is gaining interest. Such methods can sift through large volumes of candidate sequences and reduce lab screening costs. Results Here we introduce AMPlify, an attentive deep learning model for AMP prediction, and demonstrate its utility in prioritizing peptide sequences derived from the Rana [Lithobates] catesbeiana (bullfrog) genome. We tested the bioactivity of our predicted peptides against a panel of bacterial species, including representatives from the World Health Organization's priority pathogens list. Four of our novel AMPs were active against multiple species of bacteria, including a multi-drug resistant isolate of carbapenemase-producing Escherichia coli. Conclusions We demonstrate the utility of deep learning based tools like AMPlify in our fight against antibiotic resistance. We expect such tools to play a significant role in discovering novel candidates of peptide-based alternatives to classical antibiotics.
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页数:15
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