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Although metagenomic datasets are increasingly available, identifying viruses in them is challenging due to poor representation and annotation of viral sequences in databases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Here, we establish efam, an expanded collection of Hidden Markov Model (HMM) profiles that represent viral protein families conservatively identified from the Global Ocean Virome 2.0 dataset. This resulted in 240 311 HMM profiles, each with at least 2 protein sequences, making efam &amp;gt;7-fold larger than the next largest, pan-ecosystem viral HMM profile database. Adjusting the criteria for viral contig confidence from \u2018conservative\u2019 to \u2018eXtremely Conservative\u2019 resulted in 37 841 HMM profiles in our efam-XC database. To assess the value of this resource, we integrated efam-XC into VirSorter viral discovery software to discover viruses from less-studied, ecologically distinct oxygen minimum zone (OMZ) marine habitats. This expanded database led to an increase in viruses recovered from every tested OMZ virome by \u223c24% on average (up to \u223c42%) and especially improved the recovery of often-missed shorter contigs (&amp;lt;5\u2009kb). Additionally, to help elucidate lesser-known viral protein functions, we annotated the profiles using multiple databases from the DRAM pipeline and virion-associated metaproteomic data, which doubled the number of annotations obtainable by standard, single-database annotation approaches. Together, these marine resources (efam and efam-XC) are provided as searchable, compressed HMM databases that will be updated bi-annually to help maximize viral sequence discovery and study from any ecosystem.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The resources are available on the iVirus platform at (doi.org\/10.25739\/9vze-4143).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab451","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T11:12:37Z","timestamp":1623841957000},"page":"4202-4208","source":"Crossref","is-referenced-by-count":30,"title":["efam: an <i>e<\/i>xpanded, metaproteome-supported HMM profile database of viral protein <i>fam<\/i>ilies"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2793-2679","authenticated-orcid":false,"given":"Ahmed A","family":"Zayed","sequence":"first","affiliation":[{"name":"Department of Microbiology, The Ohio State University , Columbus, OH 43210, USA"},{"name":"Center of Microbiome Science, The Ohio State University , Columbus, OH 43210, USA"}]},{"given":"Dominik","family":"L\u00fccking","sequence":"additional","affiliation":[{"name":"Max-Planck-Institut fuer Marine Mikrobiologie , Bremen 28359, Germany"}]},{"given":"Mohamed","family":"Mohssen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The Ohio State University , Columbus, OH 43210, USA"},{"name":"Center of Microbiome Science, The Ohio State University , Columbus, OH 43210, USA"},{"name":"The Interdisciplinary Biophysics Graduate Program, The Ohio State University , Columbus, OH 43210, USA"}]},{"given":"Dylan","family":"Cronin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The Ohio State University , Columbus, OH 43210, USA"}]},{"given":"Ben","family":"Bolduc","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The Ohio State University , Columbus, OH 43210, USA"}]},{"given":"Ann C","family":"Gregory","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Rega Institute, KU Leuven , Leuven 3000, Belgium"},{"name":"VIB-KU Leuven Center for Microbiology , Leuven, Belgium"}]},{"given":"Katherine R","family":"Hargreaves","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The Ohio State University , Columbus, OH 43210, USA"},{"name":"Department of Life Sciences, Manchester Metropolitan University , Manchester M1 5GD, UK"}]},{"given":"Paul D","family":"Piehowski","sequence":"additional","affiliation":[{"name":"Earth and Biological Sciences Directorate, PNNL , Richland, WA 99354, USA"}]},{"given":"Richard A","family":"White III","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Genomics, The University of North Carolina at Charlotte 9201 University City Boulevard , Charlotte, NC 28223, USA"},{"name":"Department of Bioinformatics and Genomics, The University of North Carolina at Charlotte 150 Research Campus Drive , Kannapolis, NC 28081, USA"},{"name":"Australian Centre for Astrobiology, University of New South Wales , Sydney, NSW 2052, Australia"},{"name":"RAW Molecular Systems (RAW), INC , Concord, NC 28025, USA"}]},{"given":"Eric L","family":"Huang","sequence":"additional","affiliation":[{"name":"Earth and Biological Sciences Directorate, PNNL , Richland, WA 99354, USA"}]},{"given":"Joshua N","family":"Adkins","sequence":"additional","affiliation":[{"name":"Earth and Biological Sciences Directorate, PNNL , Richland, WA 99354, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-5895","authenticated-orcid":false,"given":"Simon","family":"Roux","sequence":"additional","affiliation":[{"name":"DOE Joint Genome Institute, Lawrence Berkeley National Laboratory , Berkeley, CA 94720, USA"}]},{"given":"Cristina","family":"Moraru","sequence":"additional","affiliation":[{"name":"The Institute for Chemistry and Biology of the Marine Environment (ICBM), University of Oldenburg , Oldenburg 26111, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8398-8234","authenticated-orcid":false,"given":"Matthew B","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The Ohio State University , Columbus, OH 43210, USA"},{"name":"Center of Microbiome Science, The Ohio State University , Columbus, OH 43210, USA"},{"name":"The Interdisciplinary Biophysics Graduate Program, The Ohio State University , Columbus, OH 43210, USA"},{"name":"Department of Civil, Environmental and Geodetic 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