{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T17:16:44Z","timestamp":1783358204350,"version":"3.54.6"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":169,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI087520"],"award-info":[{"award-number":["R01AI087520"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Los Alamos National Laboratory","award":["20230873PRD4"],"award-info":[{"award-number":["20230873PRD4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Understanding how virus sequences are shaped by selection can inform vaccine design and transmission inference. Modeling within-host evolution to interrogate these questions requires a detailed mechanistic framework that accurately captures sequence diversification. The CD8+ cytotoxic T-lymphocyte (CTL) response plays an important role in immune-mediated selection and can leave strong signatures in virus sequences; however, existing sequence-based within-host virus modeling frameworks do not explicitly include a human leukocyte antigen (HLA)-aware CTL response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We extended our previously published within-host sequence evolution simulator, wavess, to include an explicit CTL response, and share a method for identifying HLA-specific CTL epitopes given a founder virus sequence. We also updated the model to permit a variable recombination rate, which allows for modeling non-adjacent genes, segmented genomes, and recombination hotspots. These extensions to wavess allow for more accurate simulation of viruses and virus genes, particularly in regions of the genome where the immune response is dominated by CTLs (rather than antibodies). It also provides the foundation for investigations of how these newly-added biological mechanisms influence within-host evolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The core of wavess is written in Python 3, with helper functions written in R. It is available at https:\/\/github.com\/MolEvolEpid\/wavess.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioadv\/vbag174","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T16:37:52Z","timestamp":1781627872000},"source":"Crossref","is-referenced-by-count":0,"title":["wavess 1.2: presenting an HLA-aware within-host virus sequence simulation framework"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4674-2176","authenticated-orcid":false,"given":"Zena","family":"Lapp","sequence":"first","affiliation":[{"name":"Theoretical Biology and Biophysics, Los Alamos National Laboratory , Los Alamos, NM,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8160-2588","authenticated-orcid":false,"given":"Thomas","family":"Leitner","sequence":"additional","affiliation":[{"name":"Theoretical Biology and Biophysics, Los Alamos National Laboratory , Los Alamos, NM,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"2026070612361500800_vbag174-B1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fgene.2013.00009","article-title":"Computer programs and methodologies for the simulation of DNA sequence data with recombination","volume":"4","author":"Arenas","year":"2013","journal-title":"Front Genet"},{"key":"2026070612361500800_vbag174-B2","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.tim.2014.12.008","article-title":"HIV-1 adaptation to HLA: a window into virus\u2013host immune interactions","volume":"23","author":"Carlson","year":"2015","journal-title":"Trends Microbiol"},{"key":"2026070612361500800_vbag174-B3","doi-asserted-by":"crossref","first-page":"e12303","DOI":"10.1371\/journal.pone.0012303","article-title":"Transmission of single HIV-1 genomes and dynamics of early immune escape revealed by ultra-deep sequencing","volume":"5","author":"Fischer","year":"2010","journal-title":"PLoS One"},{"key":"2026070612361500800_vbag174-B4","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1084\/jem.20090365","article-title":"The first T cell response to transmitted\/founder virus contributes to the control of acute viremia in HIV-1 infection","volume":"206","author":"Goonetilleke","year":"2009","journal-title":"J Exp Med"},{"key":"2026070612361500800_vbag174-B5","doi-asserted-by":"crossref","first-page":"vez003","DOI":"10.1093\/ve\/vez003","article-title":"SANTA-SIM: simulating viral sequence evolution dynamics under selection and recombination","volume":"5","author":"Jariani","year":"2019","journal-title":"Virus Evol"},{"key":"2026070612361500800_vbag174-B6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1128\/JVI.01231-06","article-title":"Rapid reversion of sequence polymorphisms dominates early human immunodeficiency virus type 1 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epitope","volume":"78","author":"Peyerl","year":"2004","journal-title":"J Virol"},{"key":"2026070612361500800_vbag174-B10","doi-asserted-by":"crossref","first-page":"W449","DOI":"10.1093\/nar\/gkaa379","article-title":"NetMHCpan-4.1 and NetMHCiipan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data","volume":"48","author":"Reynisson","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2026070612361500800_vbag174-B11","doi-asserted-by":"crossref","first-page":"e1013437","DOI":"10.1371\/journal.pcbi.1013437","article-title":"Wavess: an R package for simulation of adaptive within-host virus sequence evolution","volume":"21","author":"Sambaturu","year":"2025","journal-title":"PLoS Comput Biol"},{"key":"2026070612361500800_vbag174-B12","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jim.2014.01.004","article-title":"Development of a contemporary globally diverse HIV viral panel by the 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