{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T17:43:12Z","timestamp":1733334192821,"version":"3.30.1"},"update-to":[{"updated":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"DOI":"10.1371\/journal.pcbi.1012131","type":"new_version","source":"publisher","label":"New version"}],"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Machine Learning - New Perspectives for Science","award":["EXC 2064\/1 - 390727645"]},{"name":"BMBF","award":["FKZ: 01IS18039A"]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"Immunization through repeated direct venous inoculation of Plasmodium falciparum<\/jats:italic> (Pf) sporozoites (PfSPZ) under chloroquine chemoprophylaxis, using the PfSPZ Chemoprophylaxis Vaccine (PfSPZ-CVac), induces high-level protection against controlled human malaria infection (CHMI). Humoral and cellular immunity contribute to vaccine efficacy but only limited information about the implicated Pf-specific antigens is available. Here, we examined Pf-specific antibody profiles, measured by protein arrays representing the full Pf proteome, of 40 placebo- and PfSPZ-immunized malaria-na\u00efve volunteers from an earlier published PfSPZ-CVac dose-escalation trial. For this purpose, we both utilized and adapted supervised machine learning methods to identify predictive antibody profiles at two different time points: after immunization and before CHMI. We developed an adapted multitask support vector machine (SVM) approach and compared it to standard methods, i.e. single-task SVM, regularized logistic regression and random forests. Our results show, that the multitask SVM approach improved the classification performance to discriminate the protection status based on the underlying antibody-profiles while combining time- and dose-dependent data in the prediction model. Additionally, we developed the new fE<\/jats:underline><\/jats:italic>ature diS<\/jats:underline><\/jats:italic>tance exP<\/jats:underline><\/jats:italic>lainabilitY<\/jats:underline><\/jats:italic> (ESPY) method to quantify the impact of single antigens on the non-linear multitask SVM model and make it more interpretable. In conclusion, our multitask SVM model outperforms the studied standard approaches in regard of classification performance. Moreover, with our new explanation method ESPY, we were able to interpret the impact of Pf-specific antigen antibody responses that predict sterile protective immunity against CHMI after immunization. The identified Pf-specific antigens may contribute to a better understanding of immunity against human malaria and may foster vaccine development.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012131","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T18:20:29Z","timestamp":1717784429000},"page":"e1012131","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Machine learning prediction of malaria vaccine efficacy based on antibody 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G.","family":"Kremsner","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9101-2768","authenticated-orcid":true,"given":"Benjamin","family":"Mordm\u00fcller","sequence":"additional","affiliation":[]},{"given":"Nico","family":"Pfeifer","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"volume-title":"World malaria report 2023","year":"2023","author":"WHO","key":"pcbi.1012131.ref001"},{"issue":"3","key":"pcbi.1012131.ref002","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nm0398-358","article-title":"Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria","volume":"4","author":"PC Bull","year":"1998","journal-title":"Nature medicine"},{"issue":"1","key":"pcbi.1012131.ref003","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1128\/CMR.00025-08","article-title":"Acquired immunity to malaria","volume":"22","author":"DL Doolan","year":"2009","journal-title":"Clinical microbiology reviews"},{"key":"pcbi.1012131.ref004","first-page":"197","volume-title":"Seminars in diagnostic pathology","author":"HM Wu","year":"2019"},{"issue":"3","key":"pcbi.1012131.ref005","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1097\/00000441-197309000-00002","article-title":"Immunization of man against sporozoite-induced falciparum malaria","volume":"266","author":"DF CLYDE","year":"1973","journal-title":"American journal of medical sciences"},{"issue":"1","key":"pcbi.1012131.ref006","doi-asserted-by":"crossref","first-page":"e00027","DOI":"10.1128\/mSphereDirect.00027-19","article-title":"Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis","volume":"4","author":"JM Obiero","year":"2019","journal-title":"Msphere"},{"issue":"6152","key":"pcbi.1012131.ref007","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1126\/science.1241800","article-title":"Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine","volume":"341","author":"RA Seder","year":"2013","journal-title":"Science"},{"issue":"7642","key":"pcbi.1012131.ref008","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature21060","article-title":"Sterile protection against human malaria by chemoattenuated PfSPZ vaccine","volume":"542","author":"B Mordm\u00fcller","year":"2017","journal-title":"Nature"},{"issue":"7866","key":"pcbi.1012131.ref009","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41586-021-03684-z","article-title":"Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity","volume":"595","author":"A Mwakingwe-Omari","year":"2021","journal-title":"Nature"},{"issue":"1","key":"pcbi.1012131.ref010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-021-22740-w","article-title":"Heterologous protection against malaria by a simple chemoattenuated PfSPZ vaccine regimen in a randomized trial","volume":"12","author":"Z Sulyok","year":"2021","journal-title":"Nature communications"},{"issue":"2","key":"pcbi.1012131.ref011","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1467-9868.2005.00503.x","article-title":"Regularization and variable selection via the elastic net","volume":"67","author":"H Zou","year":"2005","journal-title":"Journal of the Royal Statistical Society: Series B (Statistical Methodology)"},{"issue":"10","key":"pcbi.1012131.ref012","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1074\/mcp.M113.036632","article-title":"Predicting antidisease immunity using proteome arrays and sera from children naturally exposed to 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A survey on multi-task learning. arXiv preprint arXiv:170708114. 2017;."},{"issue":"2","key":"pcbi.1012131.ref015","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1084\/jem.20121970","article-title":"Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies","volume":"210","author":"MF Muellenbeck","year":"2013","journal-title":"Journal of Experimental Medicine"},{"key":"pcbi.1012131.ref016","doi-asserted-by":"crossref","unstructured":"Bol\u00f3n-Canedo V, S\u00e1nchez-Maro\u00f1o N, Alonso-Betanzos A. On the effectiveness of discretization on gene selection of microarray data. In: The 2010 International Joint Conference on Neural Networks (IJCNN). 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Available from: https:\/\/github.com\/slundberg\/shap."}],"updated-by":[{"updated":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"DOI":"10.1371\/journal.pcbi.1012131","type":"new_version","source":"publisher","label":"New version"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012131","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T17:50:03Z","timestamp":1718905803000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012131"}},"subtitle":[],"editor":[{"given":"Andrew J.","family":"Yates","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2024,6,7]]},"references-count":50,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1012131","relation":{},"ISSN":["1553-7358"],"issn-type":[{"type":"electronic","value":"1553-7358"}],"subject":[],"published":{"date-parts":[[2024,6,7]]}}}