{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:59:27Z","timestamp":1792155567646,"version":"4.4.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T00:00:00Z","timestamp":1720310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T00:00:00Z","timestamp":1720310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Clinical metagenomics involves the genomic sequencing of all microorganisms in clinical samples ideally after depletion of human DNA to increase sensitivity and reduce turnaround times. Current human DNA depletion methods preferentially preserve either DNA or RNA containing microbes, but not both simultaneously. Here we describe and present data using a practical and rapid mechanical host-depletion method allowing simultaneous detection of RNA and DNA microorganisms linked with nanopore sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The human cells from respiratory samples are lysed mechanically using 1.4\u2009mm zirconium-silicate spheres and the human DNA is depleted using a nonspecific endonuclease. The RNA is converted to dsDNA to allow the simultaneous sequencing of DNA and RNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The method decreases human DNA concentration by a median of eight Ct values while detecting a broad range of RNA &amp; DNA viruses, bacteria, including atypical pathogens (\n                      <jats:italic>Legionella<\/jats:italic>\n                      ,\n                      <jats:italic>Chlamydia<\/jats:italic>\n                      ,\n                      <jats:italic>Mycoplasma<\/jats:italic>\n                      ) and fungi (\n                      <jats:italic>Candida, Pneumocystis, Aspergillus<\/jats:italic>\n                      ). The first automated reports are generated after 30\u2009min sequencing from a 7\u2009h end-to-end workflow. Sensitivity and specificity for bacterial detection are 90% and 100%, respectively, and viral detection are 92% and 100% after 2\u2009h of sequencing. Prospective validation on 33 consecutive lower respiratory tract samples from ventilated patients with suspected pneumonia shows 60% concordance with routine testing, detection of additional pathogens in 21% of samples and pathogen genomic assembly achieve for 42% of viruses and 33% of bacteria.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although further workflow refinement and validation on samples containing a broader range of pathogens is required, it holds promise as a clinically deployable workflow suitable for evaluation in routine microbiology laboratories.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s43856-024-00554-3","type":"journal-article","created":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T08:01:28Z","timestamp":1720339288000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Unified metagenomic method for rapid detection of microorganisms in clinical samples"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3145-0376","authenticated-orcid":false,"given":"Adela","family":"Alcolea-Medina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Alder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke B.","family":"Snell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Themoula","family":"Charalampous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alp","family":"Aydin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7524-1947","authenticated-orcid":false,"given":"Gaia","family":"Nebbia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Goldenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Douthwaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Batra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6558-6039","authenticated-orcid":false,"given":"Penelope R.","family":"Cliff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-2578","authenticated-orcid":false,"given":"Hannah","family":"Mischo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3306-5831","authenticated-orcid":false,"given":"Stuart","family":"Neil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Wilks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Edgeworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,7]]},"reference":[{"key":"554_CR1","doi-asserted-by":"crossref","unstructured":"Chiu C. 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How and when to manage respiratory infections out of hospital. Eur. Respir. Rev. 31, 31 (2022).","journal-title":"Eur. Respir. Rev."},{"key":"554_CR5","doi-asserted-by":"crossref","unstructured":"Bailey, A. L., Ledeboer N. & Burnham C. A. D. Clinical microbiology is growing up: the total laboratory automation revolution. Clinical Chemistry. (American Association for Clinical Chemistry Inc., 2019). vol 65, pp. 634\u2013643.","DOI":"10.1373\/clinchem.2017.274522"},{"key":"554_CR6","doi-asserted-by":"crossref","unstructured":"Shi, Y. Wang, G. Lau, H. C. & Yu, J. Metagenomic sequencing for microbial DNA in human samples: emerging technological advances. Int. J. Mol. Sci. 23, 2181 (2022).","DOI":"10.3390\/ijms23042181"},{"key":"554_CR7","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.mimet.2016.05.022","volume":"127","author":"M Thoendel","year":"2016","unstructured":"Thoendel, M. et al. 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Heliyon 9, e19854 (2023).","journal-title":"Heliyon"}],"updated-by":[{"DOI":"10.1038\/s43856-024-00579-8","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000}}],"container-title":["Communications Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s43856-024-00554-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43856-024-00554-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43856-024-00554-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T02:06:16Z","timestamp":1722045976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s43856-024-00554-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,7]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["554"],"URL":"https:\/\/doi.org\/10.1038\/s43856-024-00554-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3148464\/v1","asserted-by":"object"}]},"ISSN":["2730-664X"],"issn-type":[{"value":"2730-664X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,7]]},"assertion":[{"value":"29 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2024","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s43856-024-00579-8","URL":"https:\/\/doi.org\/10.1038\/s43856-024-00579-8","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare the following competing interests: J.D.E. is employed as VP of Medical Affairs at Oxford Nanopore Technologies. Guy\u2019s & St Thomas\u2019 NHS Foundation Trust signed a commercial collaboration agreement with Oxford Nanopore Technology in September 2022. This mechanical human DNA depletion method (Fig.\u00a0\n                      \n                      ) is patent pending (PCT\/GB2023\/051417)","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"135"}}