{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T15:41:28Z","timestamp":1774539688009,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012188","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000}}],"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["213494\/Z\/18\/Z"],"award-info":[{"award-number":["213494\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X020258\/1"],"award-info":[{"award-number":["MR\/X020258\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X020258\/1"],"award-info":[{"award-number":["MR\/X020258\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AI175941"],"award-info":[{"award-number":["1R01AI175941"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI175495"],"award-info":[{"award-number":["R01AI175495"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 A1034533"],"award-info":[{"award-number":["P01 A1034533"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>The development of a safe and efficacious vaccine that provides immunity against all four dengue virus serotypes is a priority, and a significant challenge for vaccine development has been defining and measuring serotype-specific outcomes and correlates of protection. The plaque reduction neutralisation test (PRNT) is the gold standard assay for measuring serotype-specific antibodies, but this test cannot differentiate homotypic and heterotypic antibodies and characterising the infection history is challenging. To address this, we present an analysis of pre- and post-infection antibody titres measured using the PRNT, collected from a prospective cohort of Thai children. We applied four machine learning classifiers and multinomial logistic regression to the titre data to predict the infecting serotype. The models were validated against the true infecting serotype, identified using RT-PCR. Model performance was calculated using 100 bootstrap samples of the train and out-of-sample test sets. Our analysis showed that, on average, the greatest change in titre was against the infecting serotype. However, in 53.4% (109\/204) of the subjects, the highest titre change did not correspond to the infecting serotype, including in 34.3% (11\/35) of dengue-na\u00efve individuals (although 8\/11 of these seronegative individuals were seropositive to Japanese encephalitis virus prior to their infection). The highest post-infection titres of seropositive cases were more likely to match the serotype of the highest pre-infection titre than the infecting serotype, consistent with antigenic seniority or cross-reactive boosting of pre-infection titres. Despite these challenges, the best performing machine learning algorithm achieved 76.3% (95% CI 57.9\u201389.5%) accuracy on the out-of-sample test set in predicting the infecting serotype from PRNT data. Incorporating additional spatiotemporal data improved accuracy to 80.6% (95% CI 63.2\u201394.7%), while using only post-infection titres as predictor variables yielded an accuracy of 71.7% (95% CI 57.9\u201384.2%). These results show that machine learning classifiers can be used to overcome challenges in interpreting PRNT titres, making them useful tools in investigating dengue immune dynamics, infection history and identifying serotype-specific correlates of protection, which in turn can support the evaluation of clinical trial endpoints and vaccine development.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012188","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T18:43:42Z","timestamp":1734979422000},"page":"e1012188","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Predicting the infecting dengue serotype from antibody titre data using machine learning"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3707-5706","authenticated-orcid":true,"given":"Bethan","family":"Cracknell Daniels","sequence":"first","affiliation":[]},{"given":"Darunee","family":"Buddhari","sequence":"additional","affiliation":[]},{"given":"Taweewun","family":"Hunsawong","sequence":"additional","affiliation":[]},{"given":"Sopon","family":"Iamsirithaworn","sequence":"additional","affiliation":[]},{"given":"Aaron R.","family":"Farmer","sequence":"additional","affiliation":[]},{"given":"Derek A. 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