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In general, computational vaccine design includes three major stages: (i) identification and annotation of experimentally verified gold standard protective antigens through literature mining, (ii) rational vaccine design using reverse vaccinology (RV) and structural vaccinology (SV) and (iii) post-licensure vaccine success and adverse event surveillance and its usage for vaccine design. Protegen is a database of experimentally verified protective antigens, which can be used as gold standard data for rational vaccine design. RV predicts protective antigen targets primarily from genome sequence analysis. SV refines antigens through structural engineering. Recently, RV and SV approaches, with the support of various machine learning methods, have been applied to COVID-19 vaccine design. The analysis of post-licensure vaccine adverse event report data also provides valuable results in terms of vaccine safety and how vaccines should be used or paused. Ontology standardizes and incorporates heterogeneous data and knowledge in a human- and computer-interpretable manner, further supporting machine learning and vaccine design. Future directions on rational vaccine design are discussed.<\/jats:p>","DOI":"10.1093\/bib\/bbac190","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T22:21:32Z","timestamp":1654122092000},"source":"Crossref","is-referenced-by-count":20,"title":["COVID-19 vaccine design using reverse and structural vaccinology, ontology-based literature mining and machine learning"],"prefix":"10.1093","volume":"23","author":[{"given":"Anthony","family":"Huffman","sequence":"first","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan Medical School , Ann Arbor, Michigan 48109 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edison","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan Medical School , Ann Arbor, Michigan 48109 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junguk","family":"Hur","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks , North Dakota 58202 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adonis","family":"D\u2019Mello","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine , Baltimore, MD 21201 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herv\u00e9","family":"Tettelin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine , Baltimore, MD 21201 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9189-9661","authenticated-orcid":false,"given":"Yongqun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan Medical School , Ann Arbor, Michigan 48109 , USA"},{"name":"Unit for Laboratory Animal Medicine, Department of Microbiology and Immunology, Center for Computational Medicine and Bioinformatics, University of Michigan Medical School , Ann Arbor, Michigan 48109 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"2022071905583412200_ref1","article-title":"Cov19VaxKB: a web-based integrative COVID-19 vaccine knowledge base","volume":"10","author":"Huang","journal-title":"Vaccine"},{"key":"2022071905583412200_ref2","volume-title":"Roitt's Essential 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