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

Journal: Antimicrobial agents and chemotherapy
PMID:

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 from WGS and gene expression data. Antimicrobial susceptibility testing (AST) was performed using the broth microdilution method for 10 antimicrobial agents. 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 .

Authors

  • Huiqiong Jia
    Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Xinyang Li
    National Heart and Lung Institute, Hammersmith Campus, Imperial College London, 72 Du Cane Road, W12 0HS, London, UK.
  • Yilu Zhuang
    Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Yuye Wu
    Department of Urology, Fujian Second People's Hospital, Fuzhou, China.
  • Shasha Shi
    Department of Laboratory Medicine, Wuyi First People's Hospital, Jinhua, China.
  • Qingyang Sun
    Department of Clinical Laboratory, No. 903 Hospital of PLA Joint Logistic Support Force, Hangzhou, China.
  • Fang He
    Department of Applied Mathematics, The Hong Kong Polytechnic University, Hong Kong.
  • Shanyan Liang
    Department of Clinical Laboratory, Ningbo No.2 Hospital, Ningbo, China.
  • Jianfeng Wang
  • Mohamed S Draz
    Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Xinyou Xie
    Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Jun Zhang
    First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
  • Qing Yang
    School of Nursing, Chengdu Medical College, Chengdu, China.
  • Zhi Ruan
    Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.