Neural network-based predictions of antimicrobial resistance phenotypes in multidrug-resistant Acinetobacter baumannii from whole genome sequencing and gene expression

基于全基因组测序和基因表达的神经网络预测多重耐药鲍曼不动杆菌的抗菌药物耐药表型

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作者:Huiqiong Jia #,Xinyang Li #,Yilu Zhuang,Yuye Wu,Shasha Shi,Qingyang Sun,Fang He,Shanyan Liang,Jianfeng Wang,Mohamed S Draz,Xinyou Xie,Jun Zhang,Qing Yang,Zhi Ruan

Abstract

Whole genome sequencing (WGS) potentially represents a rapid approach for antimicrobial resistance genotype-to-phenotype prediction. However, the challenge still exists to predict fully minimum inhibitory concentrations (MICs) and antimicrobial susceptibility phenotypes based on WGS data. This study aimed to establish an artificial intelligence-based computational approach in predicting antimicrobial susceptibilities of multidrug-resistant Acinetobacter baumannii from WGS and gene expression data. Antimicrobial susceptibility testing (AST) was performed using the broth microdilution method for 10 antimicrobial agents. In silico multilocus sequence typing (MLST), antimicrobial resistance genes, and phylogeny based on cgSNP and cgMLST strategies were analyzed. High-throughput qPCR was performed to measure the expression level of antimicrobial resistance (AMR) genes. Most isolates exhibited a high level of resistance to most of the tested antimicrobial agents, with the majority belonging to the IC2/CC92 lineage. Phylogenetic analysis revealed undetected transmission events or local outbreaks. The percentage agreements between AMR phenotype and genotype ranged from 70.08% to 89.96%, with the coefficient of agreement (κ) extending from 0.025 and 0.881. The prediction of AST employed by deep neural network models achieved an accuracy of up to 98.64% on the testing data set. Additionally, several linear regression models demonstrated high prediction accuracy, reaching up to 86.15% within an error range of one gradient, indicating a linear relationship between certain gene expressions and the corresponding antimicrobial MICs. In conclusion, neural network-based predictions could be used as a tool for the surveillance of antimicrobial resistance in multidrug-resistant A. baumannii.

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