宏基因组高通量测序技术的临床应用：现状、挑战与前景

刁振丽; 李金明

doi:10.12290/xhyxzz.2023-0089

宏基因组高通量测序技术的临床应用：现状、挑战与前景

doi: 10.12290/xhyxzz.2023-0089

刁振丽^{1, 2},
李金明^{1, 2, ,}

1.
北京医院国家老年医学中心国家卫生健康委临床检验中心中国医学科学院老年医学研究院，北京 100730
2.
国家卫生健康委临床检验中心/北京协和医学院/中国医学科学院，北京 100730

详细信息

通讯作者:
李金明, E-mail: jmli@nccl.org.cn

中图分类号: R446.5; R51
计量
- 文章访问数: 2463
- HTML全文浏览量: 215
- PDF下载量: 498
- 被引次数: 0
出版历程
- 收稿日期: 2023-02-17
- 录用日期: 2023-03-20
- 网络出版日期: 2023-03-29
- 刊出日期: 2023-09-30

Metagenomic Next-generation Sequencing: Current Status, Challenges and Prospects of Clinical Application

DIAO Zhenli^{1, 2},
LI Jinming^{1, 2
, ,}

1.
National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing 100730, China
2.
National Center for Clinical Laboratories, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

More Information

Corresponding author: LI Jinming, E-mail: jmli@nccl.org.cn

摘要

摘要: 传统微生物学检测方法难以满足临床复杂多变的病原体检测需求。近年来，新兴的宏基因组高通量测序(metagenomic next-generation sequencing, mNGS)技术被广泛应用于各种感染性疾病诊断、新发及突发传染病病因分析、耐药基因检测和宿主免疫应答分析等领域。mNGS检测流程十分复杂，检测过程中每一步骤引入的变异均会影响检测结果的准确性。检测方法缺乏标准化、人员认知和能力不足、仪器试剂成本高昂是mNGS临床推广面临的主要障碍，因此亟需对检测方法进行标准化、规范化，快速提升检测人员的认知和综合能力。未来，整合mNGS病原体信息、转录组信息和耐药基因信息以提高对感染性疾病患者的临床管理水平是mNGS检测的重要发展方向。
- 宏基因组 /
- 高通量测序 /
- 感染 /
- 标准化
Abstract: Traditional microbial detection methods have difficulty meeting the needs of pathogen detection in the clinic. In recent years, metagenomic next-generation sequencing (mNGS) technology has emerged and been widely used in the diagnosis of various infectious diseases, the etiological analysis of emerging infectious diseases, the detection of drug resistance genes and the analysis of the host immune response. However, the mNGS workflow is complicated, and the variation introduced in each step will influence the accuracy of the detection results. In addition, the absence of standardized methods, the lack of personnel knowledge and ability, and the high cost of instruments and reagents are also creating main obstacles to the clinical application of mNGS. Therefore, standardization and normalization of methods as well as improvement of personnel knowledge and ability are urgently needed for mNGS detection. The integration of pathogen, transcriptome and antibiotic resistance genes information to comprehensively improve the clinical management of patients with infectious diseases is an important direction of mNGS detection.
- metagenomic /
- next-generation sequencing /
- infectious /
- standardized
注释:

作者贡献：刁振丽负责资料收集和论文撰写；李金明负责选题设计并审阅定稿。

利益冲突：所有作者均声明不存在利益冲突

HTML全文

参考文献(34)

[1]	Marais G, Hardie D, Brink A. A case for investment in clinical metagenomics in low-income and middle-income countries[J]. Lancet Microbe, 2023, 4: e192-e199. doi: 10.1016/S2666-5247(22)00328-7
[2]	韩东升, 马筱玲, 吴文娟. 病原体宏基因组高通量测序医院实验室本地化之路: 现状和挑战[J]. 中华检验医学杂志, 2022, 45: 100-104. https://www.cnki.com.cn/Article/CJFDTOTAL-GDGJ202305023.htm
[3]	Chiu CY, Miller SA. Clinical metagenomics[J]. Nat Rev Genet, 2019, 20: 341-355. doi: 10.1038/s41576-019-0113-7
[4]	Han D, Diao Z, Lai H, et al. Multilaboratory assessment of metagenomic next-generation sequencing for unbiased microbe detection[J]. J Adv Res, 2022, 38: 213-222. doi: 10.1016/j.jare.2021.09.011
[5]	Miller S, Naccache SN, Samayoa E, et al. Laboratory validation of a clinical metagenomic sequencing assay for pathogen detection in cerebrospinal fluid[J]. Genome Res, 2019, 29: 831-842. doi: 10.1101/gr.238170.118
[6]	Wilson MR, Sample HA, Zorn KC, et al. Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis[J]. N Engl J Med, 2019, 380: 2327-2340. doi: 10.1056/NEJMoa1803396
[7]	Diao Z, Lai H, Han D, et al. Validation of a Metagenomic Next-Generation Sequencing Assay for Lower Respiratory Pathogen Detection[J]. Microbiol Spectr, 2022: e0381222.
[8]	Diao Z, Han D, Zhang R, et al. Metagenomics next-generation sequencing tests take the stage in the diagnosis of lower respiratory tract infections[J]. J Adv Res, 2022, 38: 201-212. doi: 10.1016/j.jare.2021.09.012
[9]	Chien JY, Yu CJ, Hsueh PR. Utility of Metagenomic Next-Generation Sequencing for Etiological Diagnosis of Patients with Sepsis in Intensive Care Units[J]. Microbiol Spectr, 2022, 10: e0074622. doi: 10.1128/spectrum.00746-22
[10]	Blauwkamp TA, Thair S, Rosen MJ, et al. Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease[J]. Nat Microbiol, 2019, 4: 663-674. doi: 10.1038/s41564-018-0349-6
[11]	Velmurugan G, Dinakaran V, Rajendhran J, et al. Blood Microbiota and Circulating Microbial Metabolites in Diabetes and Cardiovascular Disease[J]. Trends Endocrinol Metab, 2020, 31: 835-847. doi: 10.1016/j.tem.2020.01.013
[12]	陶悦, 傅启华, 莫茜. 病原宏基因组测序在新型冠状病毒检测中的应用与挑战[J]. 中华检验医学杂志, 2020, 43: 217-220. doi: 10.3760/cma.j.issn.1009-9158.2020.03.004
[13]	Lin B, Hui J, Mao H. Nanopore Technology and Its Applications in Gene Sequencing[J]. Biosensors (Basel), 2021, 11: 214.
[14]	Boolchandani M, D'Souza AW, Dantas G. Sequencing-based methods and resources to study antimicrobial resistance[J]. Nat Rev Genet, 2019, 20: 356-370.
[15]	Charalampous T, Kay GL, Richardson H, et al. Nanopore metagenomics enables rapid clinical diagnosis of bacterial lower respiratory infection[J]. Nat Biotechnol, 2019, 37: 783-792. doi: 10.1038/s41587-019-0156-5
[16]	Serpa PH, Deng X, Abdelghany M, et al. Metagenomic prediction of antimicrobial resistance in critically ill patients with lower respiratory tract infections[J]. Genome Med, 2022, 14: 74. doi: 10.1186/s13073-022-01072-4
[17]	中华医学会检验医学分会临床微生物学组, 中华医学会微生物学与免疫学分会临床微生物学组, 中国医疗保健国际交流促进会临床微生物与感染分会. 宏基因组高通量测序技术应用于感染性疾病病原检测中国专家共识[J]. 中华检验医学杂志, 2021, 44: 107-120.
[18]	Langelier C, Kalantar KL, Moazed F, et al. Integrating host response and unbiased microbe detection for lower respiratory tract infection diagnosis in critically ill adults[J]. Proc Natl Acad Sci U S A, 2018, 115: e12353-e12362.
[19]	Kalantar KL, Neyton L, Abdelghany M, et al. Integrated host-microbe plasma metagenomics for sepsis diagnosis in a prospective cohort of critically ill adults[J]. Nat Microbiol, 2022, 7: 1805-1816. doi: 10.1038/s41564-022-01237-2
[20]	Ramachandran PS, Ramesh A, Creswell FV, et al. Integrating central nervous system metagenomics and host response for diagnosis of tuberculosis meningitis and its mimics[J]. Nat Commun, 2022, 13: 1675. doi: 10.1038/s41467-022-29353-x
[21]	Han D, Li Z, Li R, et al. mNGS in clinical microbiology laboratories: on the road to maturity[J]. Crit Rev Microbiol, 2019, 45: 668-685. doi: 10.1080/1040841X.2019.1681933
[22]	Di H, Thor SW, Trujillo AA, et al. Comparison of nucleic acid extraction methods for next-generation sequencing of avian influenza A virus from ferret respiratory samples[J]. J Virol Methods, 2019, 270: 95-105. doi: 10.1016/j.jviromet.2019.04.014
[23]	Gryp T, Glorieux G, Joossens M, et al. Comparison of five assays for DNA extraction from bacterial cells in human faecal samples[J]. J Appl Microbiol, 2020, 129: 378-388. doi: 10.1111/jam.14608
[24]	Scharf S, Bartels A, Kondakci M, et al. Introduction of a bead beating step improves fungal DNA extraction from selected patient specimens[J]. Int J Med Microbiol, 2020, 310: 151443. doi: 10.1016/j.ijmm.2020.151443
[25]	Hasan MR, Rawat A, Tang P, et al. Depletion of Human DNA in Spiked Clinical Specimens for Improvement of Sensitivity of Pathogen Detection by Next-Generation Sequencing[J]. J Clin Microbiol, 2016, 54: 919-927. doi: 10.1128/JCM.03050-15
[26]	Lopez-Labrador FX, Brown JR, Fischer N, et al. Recommendations for the introduction of metagenomic high-throughput sequencing in clinical virology, part Ⅰ: Wet lab procedure[J]. J Clin Virol, 2021, 134: 104691. doi: 10.1016/j.jcv.2020.104691
[27]	Diao Z, Han D, Zhang R, et al. Metagenomics next-generation sequencing tests take the stage in the diagnosis of lower respiratory tract infections[J]. J Adv Res, 2022, 38: 201-212. doi: 10.1016/j.jare.2021.09.012
[28]	Grumaz S, Stevens P, Grumaz C, et al. Next-generation sequencing diagnostics of bacteremia in septic patients[J]. Genome Med, 2016, 8: 73. doi: 10.1186/s13073-016-0326-8
[29]	中华医学会检验医学分会. 高通量宏基因组测序技术检测病原微生物的临床应用规范化专家共识[J]. 中华检验医学杂志, 2020, 43: 1181-1195.
[30]	Liu D, Zhou H, Xu T, et al. Multicenter assessment of shotgun metagenomics for pathogen detection[J]. EBioMedicine, 2021, 74: 103649. doi: 10.1016/j.ebiom.2021.103649
[31]	中华医学会检验医学分会. 宏基因组测序病原微生物检测生物信息学分析规范化管理专家共识[J]. 中华检验医学杂志, 2021, 44: 799-807.
[32]	de Vries JJC, Brown JR, Couto N, et al. Recommenda-tions for the introduction of metagenomic next-generation sequenc-ing in clinical virology, part Ⅱ: bioinformatic analysis and reporting[J]. J Clin Virol, 2021, 138: 104812.
[33]	Wilson MR, O'Donovan BD, Gelfand JM, et al. Chronic Meningitis Investigated via Metagenomic Next-Generation Sequencing[J]. JAMA Neurol, 2018, 75: 947-955.
[34]	Miao Q, Ma Y, Wang Q, et al. Microbiological Diagnostic Performance of Metagenomic Next-generation Sequencing When Applied to Clinical Practice[J]. Clin Infect Dis, 2018, 67: s231-s240.

施引文献

资源附件(0)

访问统计

点击查看大图

计量

文章访问数: 2463
HTML全文浏览量: 215
PDF下载量: 498
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

地址：	北京市东城区帅府园1号北京协和医院老楼7号楼 3层302室《协和医学杂志》编辑部
电话：	010-69154261/4262
E - mail：	medj@pumch.cn mjpumch@126.com
期刊网站版权所有：	《协和医学杂志》编辑部京ICP备 11002662

留言板

宏基因组高通量测序技术的临床应用：现状、挑战与前景

doi: 10.12290/xhyxzz.2023-0089

通讯作者:
李金明, E-mail: jmli@nccl.org.cn

计量

Metagenomic Next-generation Sequencing: Current Status, Challenges and Prospects of Clinical Application

Corresponding author: LI Jinming, E-mail: jmli@nccl.org.cn

计量

目录

留言板

宏基因组高通量测序技术的临床应用：现状、挑战与前景

doi: 10.12290/xhyxzz.2023-0089

通讯作者: 李金明, E-mail: jmli@nccl.org.cn

计量

出版历程

Metagenomic Next-generation Sequencing: Current Status, Challenges and Prospects of Clinical Application

Corresponding author: LI Jinming, E-mail: jmli@nccl.org.cn

计量

出版历程

目录

通讯作者:
李金明, E-mail: jmli@nccl.org.cn