{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T23:36:42Z","timestamp":1783121802813,"version":"3.54.6"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U54AI150472"],"award-info":[{"award-number":["U54AI150472"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P30AI036214-26"],"award-info":[{"award-number":["P30AI036214-26"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["R01HG009622"],"award-info":[{"award-number":["R01HG009622"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scripps Translational Science Institute","award":["UL1TR001114-03"],"award-info":[{"award-number":["UL1TR001114-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Technical challenges remain in the sequencing of RNA viruses due to their high intra-host diversity. This bottleneck is particularly pronounced when interrogating long-range co-evolved genetic interactions given the read-length limitations of next-generation sequencing platforms. This has hampered the direct observation of these genetic interactions that code for protein-protein interfaces with relevance in both drug and vaccine development. Here we overcome these technical limitations by developing a nanopore-based long-range viral sequencing pipeline that yields accurate single molecule sequences of circulating virions from clinical samples. We demonstrate its utility in observing the evolution of individual HIV Gag-Pol genomes in response to antiviral pressure. Our pipeline, called Multi-read Hairpin Mediated Error-correction Reaction (MrHAMER), yields &amp;gt;1000s of viral genomes per sample at 99.9% accuracy, maintains the original proportion of sequenced virions present in a complex mixture, and allows the detection of rare viral genomes with their associated mutations present at &amp;lt;1% frequency. This method facilitates scalable investigation of genetic correlates of resistance to both antiviral therapy and immune pressure and enables the identification of novel host-viral and viral-viral interfaces that can be modulated for therapeutic benefit.<\/jats:p>","DOI":"10.1093\/nar\/gkab231","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T23:14:17Z","timestamp":1617232457000},"page":"e70-e70","source":"Crossref","is-referenced-by-count":18,"title":["MrHAMER yields highly accurate single molecule viral sequences enabling analysis of intra-host evolution"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5702-0852","authenticated-orcid":false,"given":"Christian M","family":"Gallardo","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1459-8221","authenticated-orcid":false,"given":"Shiyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Montiel-Garcia","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J","family":"Little","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davey\u00a0M","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA, USA"},{"name":"Veterans Affairs San Diego Healthcare System, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2874-5990","authenticated-orcid":false,"given":"Andrew L","family":"Routh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA"},{"name":"Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4995-1694","authenticated-orcid":false,"given":"Bruce E","family":"Torbett","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA"},{"name":"Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,4,13]]},"reference":[{"key":"2021070901244168100_B1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jcv.2016.03.005","article-title":"Next generation sequencing for whole genome analysis and surveillance of influenza A viruses","volume":"79","author":"McGinnis","year":"2016","journal-title":"J. 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