Multicenter assessment of shotgun metagenomics for pathogen detection
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 an...
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Elsevier
2021
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oai:doaj.org-article:8a1eca628c2443b8ae374f71aeb796cf2021-11-22T04:27:00ZMulticenter assessment of shotgun metagenomics for pathogen detection2352-396410.1016/j.ebiom.2021.103649https://doaj.org/article/8a1eca628c2443b8ae374f71aeb796cf2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352396421004424https://doaj.org/toc/2352-3964Background: 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).Donglai LiuHaiwei ZhouTeng XuQiwen YangXi MoDawei ShiJingwen AiJingjia ZhangYue TaoDonghua WenYigang TongLili RenWen ZhangShumei XieWeijun ChenWanli XingJinyin ZhaoYilan WuXianfa MengChuan OuyangZhi JiangZhikun LiangHaiqin TanYuan FangNan QinYuanlin GuanWei GaiSihong XuWenjuan WuWenhong ZhangChuntao ZhangYouchun WangElsevierarticleShotgun Metagenomics for Pathogen DetectionNext-generation SequencingMulticenter AssessmentDiagnostic PerformanceMedicineRMedicine (General)R5-920ENEBioMedicine, Vol 74, Iss , Pp 103649- (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Shotgun Metagenomics for Pathogen Detection Next-generation Sequencing Multicenter Assessment Diagnostic Performance Medicine R Medicine (General) R5-920 |
| spellingShingle |
Shotgun Metagenomics for Pathogen Detection Next-generation Sequencing Multicenter Assessment Diagnostic Performance Medicine R Medicine (General) R5-920 Donglai Liu Haiwei Zhou Teng Xu Qiwen Yang Xi Mo Dawei Shi Jingwen Ai Jingjia Zhang Yue Tao Donghua Wen Yigang Tong Lili Ren Wen Zhang Shumei Xie Weijun Chen Wanli Xing Jinyin Zhao Yilan Wu Xianfa Meng Chuan Ouyang Zhi Jiang Zhikun Liang Haiqin Tan Yuan Fang Nan Qin Yuanlin Guan Wei Gai Sihong Xu Wenjuan Wu Wenhong Zhang Chuntao Zhang Youchun Wang Multicenter assessment of shotgun metagenomics for pathogen detection |
| description |
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). |
| format |
article |
| author |
Donglai Liu Haiwei Zhou Teng Xu Qiwen Yang Xi Mo Dawei Shi Jingwen Ai Jingjia Zhang Yue Tao Donghua Wen Yigang Tong Lili Ren Wen Zhang Shumei Xie Weijun Chen Wanli Xing Jinyin Zhao Yilan Wu Xianfa Meng Chuan Ouyang Zhi Jiang Zhikun Liang Haiqin Tan Yuan Fang Nan Qin Yuanlin Guan Wei Gai Sihong Xu Wenjuan Wu Wenhong Zhang Chuntao Zhang Youchun Wang |
| author_facet |
Donglai Liu Haiwei Zhou Teng Xu Qiwen Yang Xi Mo Dawei Shi Jingwen Ai Jingjia Zhang Yue Tao Donghua Wen Yigang Tong Lili Ren Wen Zhang Shumei Xie Weijun Chen Wanli Xing Jinyin Zhao Yilan Wu Xianfa Meng Chuan Ouyang Zhi Jiang Zhikun Liang Haiqin Tan Yuan Fang Nan Qin Yuanlin Guan Wei Gai Sihong Xu Wenjuan Wu Wenhong Zhang Chuntao Zhang Youchun Wang |
| author_sort |
Donglai Liu |
| title |
Multicenter assessment of shotgun metagenomics for pathogen detection |
| title_short |
Multicenter assessment of shotgun metagenomics for pathogen detection |
| title_full |
Multicenter assessment of shotgun metagenomics for pathogen detection |
| title_fullStr |
Multicenter assessment of shotgun metagenomics for pathogen detection |
| title_full_unstemmed |
Multicenter assessment of shotgun metagenomics for pathogen detection |
| title_sort |
multicenter assessment of shotgun metagenomics for pathogen detection |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/8a1eca628c2443b8ae374f71aeb796cf |
| work_keys_str_mv |
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