{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T15:31:10Z","timestamp":1771860670574,"version":"3.50.1"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T00:00:00Z","timestamp":1643760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072241"],"award-info":[{"award-number":["82072241"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82102436"],"award-info":[{"award-number":["82102436"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LY21H190001"],"award-info":[{"award-number":["LY21H190001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Metagenomic next-generation sequencing (mNGS) enables comprehensive pathogen detection and has become increasingly popular in clinical diagnosis. The distinct pathogenic traits between strains require mNGS to achieve a strain-level resolution, but an equivocal concept of \u2018strain\u2019 as well as the low pathogen loads in most clinical specimens hinders such strain awareness. Here we introduce a metagenomic intra-species typing (MIST) tool (https:\/\/github.com\/pandafengye\/MIST), which hierarchically organizes reference genomes based on average nucleotide identity (ANI) and performs maximum likelihood estimation to infer the strain-level compositional abundance. In silico analysis using synthetic datasets showed that MIST accurately predicted the strain composition at a 99.9% average nucleotide identity (ANI) resolution with a merely 0.001\u00d7 sequencing depth. When applying MIST on 359 culture-positive and 359 culture-negative real-world specimens of infected body fluids, we found the presence of multiple-strain reached considerable frequencies (30.39%\u201393.22%), which were otherwise underestimated by current diagnostic techniques due to their limited resolution. Several high-risk clones were identified to be prevalent across samples, including Acinetobacter baumannii sequence type (ST)208\/ST195, Staphylococcus aureus ST22\/ST398 and Klebsiella pneumoniae ST11\/ST15, indicating potential outbreak events occurring in the clinical settings. Interestingly, contaminations caused by the engineered Escherichia coli strain K-12 and BL21 throughout the mNGS datasets were also identified by MIST instead of the statistical decontamination approach. Our study systemically characterized the infected body fluids at the strain level for the first time. Extension of mNGS testing to the strain level can greatly benefit clinical diagnosis of bacterial infections, including the identification of multi-strain infection, decontamination and infection control surveillance.<\/jats:p>","DOI":"10.1093\/bib\/bbac004","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T20:10:30Z","timestamp":1641327030000},"source":"Crossref","is-referenced-by-count":11,"title":["Toward accurate diagnosis and surveillance of bacterial infections using enhanced strain-level metagenomic next-generation sequencing of infected body fluids"],"prefix":"10.1093","volume":"23","author":[{"given":"Zhi","family":"Ruan","sequence":"first","affiliation":[{"name":"Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China"}]},{"given":"Shengmei","family":"Zou","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China"}]},{"given":"Zeyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China"}]},{"given":"Luhan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China"}]},{"given":"Hangfei","family":"Chen","sequence":"additional","affiliation":[{"name":"Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China"}]},{"given":"Yuye","family":"Wu","sequence":"additional","affiliation":[{"name":"Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China"}]},{"given":"Huiqiong","family":"Jia","sequence":"additional","affiliation":[{"name":"Deparment of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"}]},{"given":"Mohamed S","family":"Draz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6551-1560","authenticated-orcid":false,"given":"Ye","family":"Feng","sequence":"additional","affiliation":[{"name":"Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China"}]}],"member":"286","published-online":{"date-parts":[[2022,2,2]]},"reference":[{"key":"2022031506321433800_ref1","doi-asserted-by":"crossref","first-page":"S231","DOI":"10.1093\/cid\/ciy693","article-title":"Microbiological diagnostic performance of metagenomic next-generation sequencing when applied to clinical practice","volume":"67","author":"Miao","year":"2018","journal-title":"Clin Infect 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