{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T04:22:45Z","timestamp":1775708565275,"version":"3.50.1"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["ZK20240061"],"award-info":[{"award-number":["ZK20240061"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continuously circulates and the Omicron variants have mutated into over 2,500 lineages, predicting ensuing prevalent lineages and inflections of dominant lineages is of public health significance and study interest. Previous study has integrated genome to forecast lineage prevalence, yet overlooked the functional aspects of mutations; efforts to evaluate the functional effects of individual mutations have not extended to the lineage level. Here, we propose CoVPF, a model integrating both genomic epidemiology and deep mutational scanning (DMS) data for the receptor binding domain (RBD) of SARS-CoV-2 spike protein, to predict the prevalence of Omicron lineages. Retrospective validation demonstrated that CoVPF achieved 20.7% higher accuracy compared to previous study. Furthermore, we found that accounting for epistasis was critical, as ignoring epistasis led to a 43% decrease in forecasting accuracy. Case studies showed that CoVPF delivered more accurate and timely forecasts for lineage expansions and inflections such as EG.5.1 and XBB.1.5. CoVPF provides a paradigm for integrating\n                    <jats:italic>\n                      <jats:italic>in vitro<\/jats:italic>\n                    <\/jats:italic>\n                    functional readouts of the virus and accounting for combinatorial effects of mutations in support of public health efforts in lineage prevalence forecasting.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0335520","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T18:29:37Z","timestamp":1762194577000},"page":"e0335520","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrating genomic epidemiology and deep mutational scanning data for prevalence forecasting of SARS-CoV-2 Omicron lineages"],"prefix":"10.1371","volume":"20","author":[{"given":"Zhong-yi","family":"Lei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-min","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-lu","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-guo","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-yi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi-lin","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-gang","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-chen","family":"Bo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9465-2787","authenticated-orcid":true,"given":"Ming","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"issue":"8","key":"pone.0335520.ref001","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1001\/jama.2020.1097","article-title":"The Novel Coronavirus Originating in Wuhan, China","volume":"323","author":"AL Phelan","year":"2020","journal-title":"JAMA"},{"key":"pone.0335520.ref002","unstructured":"World Health Organization. Coronavirus disease. 2019 [cited 6 May 2023]. Available from: https:\/\/covid19.who.int\/"},{"issue":"6","key":"pone.0335520.ref003","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41579-023-00878-2","article-title":"The evolution of SARS-CoV-2","volume":"21","author":"PV Markov","year":"2023","journal-title":"Nat Rev Microbiol"},{"issue":"11","key":"pone.0335520.ref004","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1038\/s41564-020-0770-5","article-title":"A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology","volume":"5","author":"A Rambaut","year":"2020","journal-title":"Nat Microbiol"},{"key":"pone.0335520.ref005","unstructured":"World Health Organization. WHO announces simple, easy-to-say labels for SARS-CoV-2 Variants of Interest and Concern. Available from: https:\/\/www.who.int\/news\/item\/31-05-2021-who-announces-simple-easy-to-say-labels-for-sars-cov-2-variants-of-interest-and-concern"},{"issue":"2","key":"pone.0335520.ref006","doi-asserted-by":"crossref","DOI":"10.1128\/spectrum.02732-21","article-title":"Update on SARS-CoV-2 Omicron Variant of Concern and Its Peculiar Mutational Profile","volume":"10","author":"M Alkhatib","year":"2022","journal-title":"Microbiol Spectr"},{"key":"pone.0335520.ref007","unstructured":"Centers for Disease Control and Prevention. SARS-CoV-2 Variant Classifications and Definitions Updated Sept. 1, 2023. Available from: https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/variants\/variant-classifications.html"},{"key":"pone.0335520.ref008","unstructured":"WIKIPEDIA. SARS-CoV-2 Omicron variant. 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Han","year":"2022","journal-title":"Cell"},{"issue":"7935","key":"pone.0335520.ref012","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/d41586-022-03445-6","article-title":"COVID \u201cvariant soup\u201d is making winter surges hard to predict","volume":"611","author":"E Callaway","year":"2022","journal-title":"Nature"},{"issue":"6584","key":"pone.0335520.ref013","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1126\/science.abn8863","article-title":"Structures of the Omicron spike trimer with ACE2 and an anti-Omicron antibody","volume":"375","author":"W Yin","year":"2022","journal-title":"Science"},{"issue":"9","key":"pone.0335520.ref014","doi-asserted-by":"crossref","DOI":"10.1002\/iid3.683","article-title":"Missense mutations in spike protein of SARS-CoV-2 delta variant contribute to the alteration in viral structure and interaction with hACE2 receptor","volume":"10","author":"TB Mahmood","year":"2022","journal-title":"Immun Inflamm 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Thadani","year":"2023","journal-title":"Nature"},{"issue":"1","key":"pone.0335520.ref024","doi-asserted-by":"crossref","first-page":"7011","DOI":"10.1038\/s41467-022-34506-z","article-title":"Compensatory epistasis maintains ACE2 affinity in SARS-CoV-2 Omicron BA.1","volume":"13","author":"A Moulana","year":"2022","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0335520.ref025","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41467-023-35927-0","article-title":"Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape","volume":"14","author":"L Witte","year":"2023","journal-title":"Nat Commun"},{"issue":"6604","key":"pone.0335520.ref026","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1126\/science.abo7896","article-title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","volume":"377","author":"TN 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EG.5 initial risk evaluation. 9 Aug 2023. Available from: https:\/\/www.who.int\/docs\/default-source\/coronaviruse\/09082023eg.5_ire_final.pdf"},{"key":"pone.0335520.ref036","unstructured":"World Health Organization. Initial Risk Evaluation of JN.1. 19 Dec 2023. 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