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As a result, understanding immunologic variation across individuals in response to vaccination is important for developing next-generation efficacious vaccines. Accurate outcome prediction and identification of predictive biomarkers would represent a significant step towards this goal. Moreover, in early phase vaccine clinical trials, small datasets are prevalent, raising the need and challenge of building a robust and explainable prediction model that can reveal heterogeneity in small datasets. We propose a new model named Generative Mixture of Logistic Regression (GeM-LR), which combines characteristics of both a generative and a discriminative model. In addition, we propose a set of model selection strategies to enhance the robustness and interpretability of the model. GeM-LR extends a linear classifier to a non-linear classifier without losing interpretability and empowers the notion of predictive clustering for characterizing data heterogeneity in connection with the outcome variable. We demonstrate the strengths and utility of GeM-LR by applying it to data from several studies. GeM-LR achieves better prediction results than other popular methods while providing interpretations at different levels.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012581","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T13:47:12Z","timestamp":1731592032000},"page":"e1012581","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["GeM-LR: Discovering predictive biomarkers for small datasets in vaccine studies"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7464-1172","authenticated-orcid":true,"given":"Lin","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel L.","family":"Spreng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2009-3270","authenticated-orcid":true,"given":"Kelly E.","family":"Seaton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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