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This limits the identification of viruses exclusively found outside the gastrointestinal tract and impairs analyses requiring high-quality genomes. To address these issues, we created the Updateable Human Virome Database (UHVDB), an expandable database of high-quality, clustered, and annotated virus genomes integrated from pre-existing human virome databases and diverse human sample metagenome assemblies. We developed an associated toolkit that enables users to 1) update by UHVDB mining, clustering, and annotating virus sequences, 2) taxonomically profile viruses in metagenomes and metatranscriptomes, 3) estimate phage replication activity using phage-to-host ratios, and 4) identify putatively uninducible prophages from bulk metagenomes. To illustrate the utility of UHVDB and its associated toolkit, we analyzed 1,983 oral\/airway samples from people with Cystic Fibrosis, finding that over 25% of viruses present were likely uninducible prophages and that many others had low replication activity, suggesting far less viral activity than estimated from previous studies. UHVDB is a novel framework for virome analysis that expands the capacity to define virus contributions to health and disease.<\/jats:p>\n                <jats:sec>\n                  <jats:title>GRAPHICAL ABSTRACT<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"722327v3_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.01.722327","type":"posted-content","created":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T03:25:17Z","timestamp":1777778717000},"source":"Crossref","is-referenced-by-count":0,"title":["The Updateable Human Virome Database and toolkit: A novel framework for human virome analysis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9861-4884","authenticated-orcid":false,"given":"Carson J.","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Washington School of Medicine, Seattle, WA, 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Pope","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Washington School of Medicine, Seattle, WA, 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot H.","family":"Lavitt","sequence":"additional","affiliation":[{"name":"Department of Earth and Planetary Science, University of California Berkeley, Berkeley, CA, 94720, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay J.","family":"Caverly","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, 48109,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"LiPuma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, 48109,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsi","family":"Penewit","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janessa D.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Salipante","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas R.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Department of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Washington School of Medicine, Seattle, WA, 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026082816200823000_2026.05.01.722327v3.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04160"},{"key":"2026082816200823000_2026.05.01.722327v3.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00637-7"},{"key":"2026082816200823000_2026.05.01.722327v3.3","doi-asserted-by":"crossref","unstructured":"Koonin, E.V. , Dolja, V.V. , Krupovic, M. , Varsani, A. , Wolf, Y.I. , Yutin, N. , Zerbini, F.M. and Kuhn, J.H . 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