{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:56:58Z","timestamp":1753883818675,"version":"3.37.3"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Wake Forest University Health Sciences"},{"name":"Wake Forest Baptist Comprehensive Cancer Center Bioinformatics Shared Resource","award":["P30CA012197"],"award-info":[{"award-number":["P30CA012197"]}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Summary<\/jats:title><jats:p>Mutation is the key for a variant of concern (VOC) to overcome selective pressures, but this process is still unclear. Understanding the association of the mutational process with VOCs is an unmet need. Motivation: Here, we developed VOC-alarm, a method to predict VOCs and their caused COVID surges, using mutations of about 5.7 million SARS-CoV-2 complete sequences. We found that VOCs rely on lineage-level entropy value of mutation numbers to compete with other variants, suggestive of the importance of population-level mutations in the virus evolution. Thus, we hypothesized that VOCs are a result of a mutational process across the globe. Results: Analyzing the mutations from January 2020 to December 2021, we simulated the mutational process by estimating the pace of evolution, and thus divided the time period, January 2020\u2014March 2022, into eight stages. We predicted Alpha, Delta, Delta Plus (AY.4.2) and Omicron (B.1.1.529) by their mutational entropy values in the Stages I, III, V and VII with accelerated paces, respectively. In late November 2021, VOC-alarm alerted that Omicron strongly competed with Delta and Delta plus to become a highly transmissible variant. Using simulated data, VOC-alarm also predicted that Omicron could lead to another COVID surge from January 2022 to March 2022.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>Our software implementation is available at https:\/\/github.com\/guangxujin\/VOC-alarm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btac370","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:43:12Z","timestamp":1654044192000},"page":"3549-3556","source":"Crossref","is-referenced-by-count":5,"title":["VOC-alarm: mutation-based prediction of SARS-CoV-2 variants of concern"],"prefix":"10.1093","volume":"38","author":[{"given":"Hongyu","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Cancer Biology, Wake Forest School of Medicine , Winston-Salem, NC 27157, USA"}]},{"given":"Kun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine , Winston-Salem, NC 27101, USA"}]},{"given":"Chao","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital , Tianjin, China"},{"name":"Tianjin Key Laboratory of Female Reproductive Health and Eugenics , Tianjin 300052, China"}]},{"given":"Vithal","family":"Madhira","sequence":"additional","affiliation":[{"name":"Palila Software LLC , Reno, NV 89521, USA"}]},{"given":"Umit","family":"Topaloglu","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Wake Forest School of Medicine , Winston-Salem, NC 27157, USA"},{"name":"Wake Forest Baptist Comprehensive Cancer Center , Winston-Salem, NC 27157, USA"},{"name":"Wake Forest School of Medicine, Center for Biomedical Informatics , NC 27101, USA"}]},{"given":"Yong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine , Winston-Salem, NC 27101, USA"},{"name":"Wake Forest Baptist Comprehensive Cancer Center , Winston-Salem, NC 27157, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9451-4886","authenticated-orcid":false,"given":"Guangxu","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Wake Forest School of Medicine , Winston-Salem, NC 27157, USA"},{"name":"Wake Forest Baptist Comprehensive Cancer Center , Winston-Salem, NC 27157, USA"}]}],"member":"286","published-online":{"date-parts":[[2022,5,31]]},"reference":[{"key":"2023041405364097100_","doi-asserted-by":"crossref","first-page":"104654","DOI":"10.1016\/j.compbiomed.2021.104654","article-title":"Investigation of nonsynonymous mutations in the spike protein of SARS-CoV-2 and its interaction with the ACE2 receptor by molecular docking and MM\/GBSA approach","volume":"135","author":"Aljindan","year":"2021","journal-title":"Comput. 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