{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:47:14Z","timestamp":1785836834287,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2026R716"],"award-info":[{"award-number":["PNURSP2026R716"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PNURSP2026R716"],"award-info":[{"award-number":["PNURSP2026R716"]}],"id":[{"id":"https:\/\/ror.org\/05b0cyh02","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) has two principal molecular subtypes\u2014classical and basal-like\u2014with divergent prognosis and chemotherapy response, yet transcriptomic classifiers rarely generalize across cohorts or quantify per-patient uncertainty. We trained a classical-versus-basal-like classifier on CPTAC-PDAC (n = 140) and externally validated it on histology-filtered TCGA-PAAD (n = 150). Twelve algorithms were benchmarked under stratified nested cross-validation with four-method consensus feature selection; domain adaptation (naive transfer, CORAL, and ComBat), four conformal procedures (split, weighted, CV+, and Conformal Risk Control), and a four-method consensus explainable-AI framework (SHAP, LIME, permutation importance, and decision-curve ablation) with pathway enrichment were then evaluated. Top models reached a cross-validated AUROC \u2248 0.96 and external AUROC 0.913\u20130.938 (top-3 ensemble 0.961); batch correction did not improve transfer, indicating minimal residual batch effect. Consensus explainability recovered keratinization biology and nominated five candidate genes (GSDMC, A2ML1, PIP5K1B, IL20RB, and AKR7L) beyond the Moffitt signature. All four conformal procedures plateaued near 0.85 coverage at \u03b1 = 0.05 under zero-shot transfer, whereas local recalibration on a small target sample restored nominal coverage. We present a transparent, externally validated, uncertainty-aware and TRIPOD+AI-compliant PDAC subtype classifier, best deployed as a calibrated decision-support tool with site-specific recalibration.<\/jats:p>","DOI":"10.3390\/ijms27156989","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:15:22Z","timestamp":1785834922000},"page":"6989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Generalizable and Interpretable Framework for Molecular Subtype Classification of Pancreatic Ductal Adenocarcinoma Integrating Conformal Uncertainty Quantification and Consensus-Based Explainable Artificial Intelligence Across Multiple Cohorts"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1300-3393","authenticated-orcid":false,"given":"Seyma","family":"Yasar","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Medical Informatics, Faculty of Medicine, \u0130n\u00f6n\u00fc University, Malatya 44280, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9848-7958","authenticated-orcid":false,"given":"Fatma Hilal","family":"Yagin","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Faculty of Medicine, Malatya Turgut Ozal University, Malatya 44210, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Alzakari","sequence":"additional","affiliation":[{"name":"Department of Computer Sciences, College of Computer and Information Sciences, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7273-4041","authenticated-orcid":false,"given":"Amal K.","family":"Alkhalifa","sequence":"additional","affiliation":[{"name":"Department of Computer Sciences, College of Computer and Information Sciences, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5795-9966","authenticated-orcid":false,"given":"Fahaid","family":"Al-Hashem","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8263-4944","authenticated-orcid":false,"given":"Abedelmalek Kalefh","family":"Tabnjh","sequence":"additional","affiliation":[{"name":"Department of Cariology, Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden"},{"name":"Department of Applied Dental Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan"},{"name":"Department of Pathology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai 602105, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA A Cancer J. 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