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Addressing the limitations of opaque deep learning architectures and the noise inherent in electronic health records, we introduce the sequential pattern transformer (SPT), a novel framework that synergizes sequential pattern mining with generative transformer modeling. Using four years of inpatient data from 258,460 type 2 diabetes patients, we applied the PrefixSpan algorithm to distill noisy diagnostic histories into a curated vocabulary of 95,630 statistically validated disease progression patterns. A decoder-only transformer was trained exclusively on these evidence-based sequences to learn the temporal dynamics of disease evolution. This pattern-guided approach shifts the modeling paradigm from classification to probabilistic trajectory generation. The model achieved a robust 85.78% Top-5 accuracy, significantly outperforming a standard LSTM baseline (71.47%). Beyond predictive accuracy, the framework constructs a dynamic Disease Atlas, a branching tree structure that visualizes likely future pathways, augmented by multi-level explainable AI (XAI) including learned clinical clusters, SHAP-based feature attribution, and counterfactual simulations. Crucially, this methodology is domain-agnostic and capable of efficient fine-tuning, making it a transferable solution for adapting to diverse clinical conditions and local hospital settings. SPT thus offers a transparent, robust, and scalable framework for mapping the complex temporal dynamics of disease, bridging the gap between high-performance AI and interpretable clinical application.<\/jats:p>","DOI":"10.1007\/s00521-025-11695-4","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T01:18:35Z","timestamp":1770081515000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sequential pattern transformer (SPT): a generative and interpretable framework for predicting disease trajectories"],"prefix":"10.1007","volume":"38","author":[{"given":"Mohammad","family":"Assadi Shalmani","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3131-0661","authenticated-orcid":false,"given":"Masoud","family":"Khani","sequence":"additional","affiliation":[]},{"given":"Amirsajjad","family":"Taleban","sequence":"additional","affiliation":[]},{"given":"Zihao","family":"Yi","sequence":"additional","affiliation":[]},{"given":"Jennifer T.","family":"Fink","sequence":"additional","affiliation":[]},{"given":"Christopher E.","family":"Weber","sequence":"additional","affiliation":[]},{"given":"Qiang","family":"Lu","sequence":"additional","affiliation":[]},{"given":"Jake","family":"Luo","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"11695_CR1","doi-asserted-by":"publisher","unstructured":"Fikri M, Hammerich A (2018) Scaling up action on the prevention and control of noncommunicable diseases in the who eastern mediterranean region. https:\/\/doi.org\/10.26719\/2018.24.1.3","DOI":"10.26719\/2018.24.1.3"},{"issue":"1","key":"11695_CR2","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.mayocpiqo.2023.08.005","volume":"8","author":"K Hacker","year":"2024","unstructured":"Hacker K (2024) The burden of chronic disease. 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Each author has thoroughly examined the manuscript\u2019s content and confirmed that any affiliations, financial involvement, or personal connections do not present a conflict of interest in the design, execution, interpretation, or reporting of the research findings. The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study involved the use of de-identified, publicly available data from the State Inpatient Database (SID) and did not involve any direct interaction with human or animal subjects. The study was approved by the Institutional Review Board of Medical College of Wisconsin and University of Wisconsin Milwaukee (IRB Approval No. MIL121118). 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