{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T06:50:07Z","timestamp":1772866207027,"version":"3.50.1"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["440685\/2016-8"],"award-info":[{"award-number":["440685\/2016-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["440856\/2016-7"],"award-info":[{"award-number":["440856\/2016-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88887.130716\/2016-00"],"award-info":[{"award-number":["88887.130716\/2016-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88881.130825\/2016-00"],"award-info":[{"award-number":["88881.130825\/2016-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88887.130823\/2016-00"],"award-info":[{"award-number":["88887.130823\/2016-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ZIKAlliance","award":["734548"],"award-info":[{"award-number":["734548"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Yellow fever virus (YFV) is the agent of the most severe mosquito-borne disease in the tropics. Recently, Brazil suffered major YFV outbreaks with a high fatality rate affecting areas where the virus has not been reported for decades, consisting of urban areas where a large number of unvaccinated people live. We developed a machine learning framework combining three different algorithms (XGBoost, random forest and regularized logistic regression) to analyze YFV genomic sequences. This method was applied to 56 YFV sequences from human infections and 27 from non-human primate (NHPs) infections to investigate the presence of genetic signatures possibly related to disease severity (in human related sequences) and differences in PCR cycle threshold (Ct) values (in NHP related sequences). Our analyses reveal four non-synonymous single nucleotide variations (SNVs) on sequences from human infections, in proteins NS3 (E614D), NS4a (I69V), NS5 (R727G, V643A) and six non-synonymous SNVs on NHP sequences, in proteins E (L385F), NS1 (A171V), NS3 (I184V) and NS5 (N11S, I374V, E641D). We performed comparative protein structural analysis on these SNVs, describing possible impacts on protein function. Despite the fact that the dataset is limited in size and that this study does not consider virus-host interactions, our work highlights the use of machine learning as a versatile and fast initial approach to genomic data exploration.<\/jats:p>","DOI":"10.1371\/journal.pone.0278982","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T18:28:16Z","timestamp":1670869696000},"page":"e0278982","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Machine learning models exploring characteristic single-nucleotide signatures in yellow fever virus"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7579-144X","authenticated-orcid":true,"given":"\u00c1lvaro","family":"Salgado","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel C. de","family":"Melo-Minardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Giovanetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriano","family":"Veloso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francielly","family":"Morais-Rodrigues","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Talita","family":"Adelino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronaldo","family":"de Jesus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephane","family":"Tosta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasco","family":"Azevedo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Lourenco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz Carlos J.","family":"Alcantara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,12,12]]},"reference":[{"issue":"1","key":"pone.0278982.ref001","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1146\/annurev.mi.44.100190.003245","article-title":"\u201cFlavivirus genome organization, expression, and replication,\u201d Annu","volume":"44","author":"T. J. Chambers","year":"1990","journal-title":"Rev. Microbiol."},{"issue":"1","key":"pone.0278982.ref002","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S1473-3099(01)00016-0","article-title":"\u201cYellow fever: an update,\u201d","volume":"1","author":"T. P. Monath","year":"2001","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"pone.0278982.ref003","first-page":"237","article-title":"\u201cYellow Fever: A Reemerging Threat,\u201d Clinics in Laboratory Medicine,","volume":"30","author":"C. L. Gardner","year":"2010"},{"issue":"1","key":"pone.0278982.ref004","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.antiviral.2007.10.009","article-title":"\u201cTreatment of yellow fever,\u201d","volume":"78","author":"T. P. Monath","year":"2008","journal-title":"Antiviral Research"},{"key":"pone.0278982.ref005","first-page":"2020","article-title":"\u201cWHO Report on Global Surveillance of Epidemic-prone Infectious Diseases\u2014Yellow fever,\u201d","volume":"02","year":"2015","journal-title":"World Health Organization"},{"key":"pone.0278982.ref006","unstructured":"\u201cYellow Fever,\u201d Pan American Health Organization \/ World Health Organization, Accessed 2020. https:\/\/www.paho.org\/hq\/index.php?option=com_topics&view=article&id=69&Itemid=40784&lang=en (accessed Jun. 29, 2020)."},{"issue":"15","key":"pone.0278982.ref007","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1056\/NEJMp1702172","article-title":"\u201cYellow Fever\u2014Once Again on the Radar Screen in the Americas,\u201d","volume":"376","author":"C. I. 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Noske","journal-title":"Biochim Biophys Acta Gen Subj"},{"key":"pone.0278982.ref039","doi-asserted-by":"crossref","first-page":"104536","DOI":"10.1016\/j.antiviral.2019.104536","article-title":"\u201cStructure of the yellow fever NS5 protein reveals conserved drug targets shared among flaviviruses,\u201d","volume":"169","author":"A. Dubankova","year":"2019","journal-title":"Antiviral Research"},{"issue":"1","key":"pone.0278982.ref040","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s13073-016-0356-2","article-title":"\u201cMobile real-time surveillance of Zika virus in Brazil,\u201d","volume":"8","author":"N. R. Faria","year":"2016","journal-title":"Genome Medicine"},{"issue":"7658","key":"pone.0278982.ref041","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/nature22401","article-title":"\u201cEstablishment and cryptic transmission of Zika virus in Brazil and the Americas,\u201d","volume":"546","author":"N. R. Faria","year":"2017","journal-title":"Nature"},{"issue":"8","key":"pone.0278982.ref042","doi-asserted-by":"crossref","first-page":"4448","DOI":"10.1021\/acs.chemrev.7b00719","article-title":"\u201cBiochemistry and Molecular Biology of Flaviviruses,\u201d","volume":"118","author":"N. J. Barrows","year":"2018","journal-title":"Chemical Reviews"},{"issue":"2","key":"pone.0278982.ref043","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.celrep.2018.12.065","article-title":"\u201cDouble Lock of a Human Neutralizing and Protective Monoclonal Antibody Targeting the Yellow Fever Virus Envelope,\u201d","volume":"26","author":"X. Lu","year":"2019","journal-title":"Cell Reports"},{"issue":"10","key":"pone.0278982.ref044","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/j.bbagen.2019.05.012","article-title":"\u201cExploitation of glycosylation in enveloped virus pathobiology,\u201d","volume":"1863","author":"Y. Watanabe","year":"2019","journal-title":"Biochimica et Biophysica Acta (BBA)\u2014General Subjects"},{"issue":"7","key":"pone.0278982.ref045","doi-asserted-by":"crossref","first-page":"e1005738","DOI":"10.1371\/journal.ppat.1005738","article-title":"\u201cDengue Virus NS1 Disrupts the Endothelial Glycocalyx, Leading to Hyperpermeability,\u201d","volume":"12","author":"H. Puerta-Guardo","year":"2016","journal-title":"PLOS Pathogens"},{"issue":"1","key":"pone.0278982.ref046","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1128\/JVI.01788-07","article-title":"\u201cCrystal Structure of the NS3 Protease-Helicase from Dengue Virus,\u201d","volume":"82","author":"D. Luo","year":"2008","journal-title":"Journal of Virology"},{"issue":"7","key":"pone.0278982.ref047","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1128\/JVI.03453-14","article-title":"\u201cCharacterization of Dengue Virus NS4A and NS4B Protein Interaction,\u201d","volume":"89","author":"J. Zou","year":"2015","journal-title":"Journal of Virology"},{"issue":"12","key":"pone.0278982.ref048","doi-asserted-by":"crossref","first-page":"8873","DOI":"10.1074\/jbc.M609919200","article-title":"\u201cThe non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner,\u201d","volume":"282","author":"S. Miller","year":"2007","journal-title":"J. Biol. Chem."},{"issue":"10","key":"pone.0278982.ref049","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1080\/07391102.2013.826599","article-title":"\u201cMembrane undulation induced by NS4A of Dengue virus: a molecular dynamics simulation study,\u201d","volume":"32","author":"M.-H. Lin","year":"2014","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"issue":"4","key":"pone.0278982.ref050","doi-asserted-by":"crossref","DOI":"10.3390\/v9040091","article-title":"\u201cDengue Virus Non-Structural Protein 5,\u201d","volume":"9","author":"A. El Sahili","year":"2017","journal-title":"Viruses"},{"key":"pone.0278982.ref051","first-page":"247255522094212","article-title":", \u201cRNA-Dependent RNA Polymerase as a Target for COVID-19 Drug Discovery,\u201d","author":"W. Zhu","year":"2020","journal-title":"SLAS DISCOVERY: Advancing the Science of Drug Discovery"},{"issue":"11","key":"pone.0278982.ref052","doi-asserted-by":"crossref","first-page":"5408","DOI":"10.1128\/JVI.02188-08","article-title":"\u201cNS5 of Dengue Virus Mediates STAT2 Binding and Degradation,\u201d","volume":"83","author":"J. Ashour","year":"2009","journal-title":"J Virol"},{"issue":"4","key":"pone.0278982.ref053","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1093\/bib\/bbx108","article-title":"\u201cMAFFT online service: multiple sequence alignment, interactive sequence choice and visualization,\u201d","volume":"20","author":"K. Katoh","year":"2019","journal-title":"Briefings in Bioinformatics"},{"issue":"5","key":"pone.0278982.ref054","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1214\/aos\/1013203451","article-title":"\u201cGreedy Function Approximation: A Gradient Boosting Machine,\u201d","volume":"29","author":"J. H. Friedman","year":"2001","journal-title":"The Annals of Statistics"},{"key":"pone.0278982.ref055","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/978-0-387-21579-2_9","volume-title":"Nonlinear Estimation and Classification","author":"R. E. Schapire","year":"2003"},{"issue":"1","key":"pone.0278982.ref056","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random forests,\u201d","volume":"45","author":"L. Breiman","year":"2001","journal-title":"Machine learning"},{"key":"pone.0278982.ref057","doi-asserted-by":"crossref","first-page":"144168","DOI":"10.1016\/j.gene.2019.144168","article-title":"Analysis of the microarray gene expression for breast cancer progression after the application modified logistic regression,\u201d","volume":"726","author":"F. Morais-Rodrigues","year":"2020","journal-title":"Gene"},{"issue":"1","key":"pone.0278982.ref058","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/pro.3730","article-title":"\u201cRCSB Protein Data Bank: Enabling biomedical research and drug discovery,\u201d","volume":"29","author":"D. S. Goodsell","year":"2020","journal-title":"Protein Sci."},{"issue":"13","key":"pone.0278982.ref059","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1093\/nar\/gkg520","article-title":"\u201cSWISS-MODEL: an automated protein homology-modeling server,\u201d","volume":"31","author":"T. Schwede","year":"2003","journal-title":"Nucleic Acids Res"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0278982","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T21:26:47Z","timestamp":1701552407000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0278982"}},"subtitle":[],"editor":[{"given":"Rakesh Kumar","family":"Verma","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,12,12]]},"references-count":59,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0278982","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,12]]}}}