Metagenomic next-generation sequencing and proteomics analysis in pediatric viral encephalitis and meningitis

Yi-Long Wang; Xiao-Tong Guo; Meng-Ying Zhu; Yu-Chen Mao; Xue-Bin Xu; Yi Hua; Lu Xu; Li-Hua Jiang; Cong-Ying Zhao; Xin Zhang; Guo-Xia Sheng; Pei-Fang Jiang; Zhe-Feng Yuan; Feng Gao

doi:10.3389/fcimb.2023.1104858

Metagenomic next-generation sequencing and proteomics analysis in pediatric viral encephalitis and meningitis

Front Cell Infect Microbiol. 2023 Apr 21:13:1104858. doi: 10.3389/fcimb.2023.1104858. eCollection 2023.

Authors

Yi-Long Wang^{1

2}, Xiao-Tong Guo^{1

2}, Meng-Ying Zhu^{1

2}, Yu-Chen Mao^{1

2}, Xue-Bin Xu^{1

2}, Yi Hua^{1

2}, Lu Xu^{1

2}, Li-Hua Jiang^{1

2}, Cong-Ying Zhao^{1

2}, Xin Zhang^{1

2}, Guo-Xia Sheng^{1

2}, Pei-Fang Jiang^{1

2}, Zhe-Feng Yuan^{1

2}, Feng Gao^{1

2}

Affiliations

¹ Department of Neurology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
² Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou, Zhejiang, China.

Abstract

Introduction: Early and accurate identification of pathogens is essential for improved outcomes in patients with viral encephalitis (VE) and/or viral meningitis (VM).

Methods: In our research, Metagenomic next-generation sequencing (mNGS) which can identify viral pathogens unbiasedly was performed on RNA and DNA to identify potential pathogens in cerebrospinal fluid (CSF) samples from 50 pediatric patients with suspected VEs and/or VMs. Then we performed proteomics analysis on the 14 HEV-positive CSF samples and another 12 CSF samples from health controls (HCs). A supervised partial least squaresdiscriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) model was performed using proteomics data.

Results: Ten viruses in 48% patients were identified and the most common pathogen was human enterovirus (HEV) Echo18. 11 proteins overlapping between the top 20 DEPs in terms of P value and FC and the top 20 proteins in PLS-DA VIP lists were acquired.

Discussion: Our result showed mNGS has certain advantages on pathogens identification in VE and VM and our research established a foundation to identify diagnosis biomarker candidates of HEV-positive meningitis based on MS-based proteomics analysis, which could also contribute toward investigating the HEV-specific host response patterns.

Keywords: MS-based proteomics; diagnostic biomarkers; human enterovirus (HEV); metagenomic next-generation sequencing (mNGS); viral encephalitis (VE); viral meningitis (VM).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Child
Encephalitis, Viral* / diagnosis
Enterovirus* / genetics
High-Throughput Nucleotide Sequencing
Humans
Meningitis, Viral* / diagnosis
Metagenomics
Proteomics
Sensitivity and Specificity
Viruses* / genetics

Grants and funding

This work was supported by the Key research and development plan of Zhejiang Province (2020C03038), Zhejiang Provincial Natural Science Foundation of China (LGF19H090020).