Multicenter assessment of shotgun metagenomics for pathogen detection
| Autor: | Wanli Xing, Xi Mo, Wen Zhang, Yue Tao, Yigang Tong, Jingjia Zhang, Chuan Ouyang, Lili Ren, Shumei Xie, Yilan Wu, Youchun Wang, Xianfa Meng, Zhikun Liang, Haiqin Tan, Jinyin Zhao, Teng Xu, Donglai Liu, Qiwen Yang, Wei Gai, Yuanlin Guan, Dawei Shi, Wenjuan Wu, Wenhong Zhang, Nan Qin, Sihong Xu, Donghua Wen, Zhi Jiang, Yuan Fang, Chuntao Zhang, Haiwei Zhou, Weijun Chen, Jing-Wen Ai |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
China
Next-generation Sequencing Medicine (General) Research paper Pathogen detection Diagnostic Performance Read depth Context (language use) Multicenter Assessment Computational biology Biology Communicable Diseases General Biochemistry Genetics and Molecular Biology Workflow R5-920 Humans Reference standards Bacteria Fungi High-Throughput Nucleotide Sequencing Reproducibility of Results Sequence Analysis DNA General Medicine Benchmarking Medicine Metagenomics Laboratories Shotgun metagenomics Shotgun Metagenomics for Pathogen Detection HeLa Cells |
| Zdroj: | EBioMedicine, Vol 74, Iss, Pp 103649-(2021) EBioMedicine |
| ISSN: | 2352-3964 |
| Popis: | Background Shotgun metagenomics has been used clinically for diagnosing infectious diseases. However, most technical assessments have been limited to individual sets of reference standards, experimental workflows, and laboratories. Methods A reference panel and performance metrics were designed and used to examine the performance of shotgun metagenomics at 17 laboratories in a coordinated collaborative study. We comprehensively assessed the reliability, key performance determinants, reproducibility, and quantitative potential. Findings Assay performance varied significantly across sites and microbial classes, with a read depth of 20 millions as a generally cost-efficient assay setting. Results of mapped reads by shotgun metagenomics could indicate relative and intra-site (but not absolute or inter-site) microbial abundance. Interpretation Assay performance was significantly impacted by the microbial type, the host context, and read depth, which emphasizes the importance of these factors when designing reference reagents and benchmarking studies. Across sites, workflows and platforms, false positive reporting and considerable site/library effects were common challenges to the assay's accuracy and quantifiability. Our study also suggested that laboratory-developed shotgun metagenomics tests for pathogen detection should aim to detect microbes at 500 CFU/mL (or copies/mL) in a clinically relevant host context (10^5 human cells/mL) within a 24h turn-around time, and with an efficient read depth of 20M. Funding This work was supported by National Science and Technology Major Project of China (2018ZX10102001). |
| Databáze: | OpenAIRE |
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