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We performed an integrative analysis of transcriptomic, genomic, and microenvironmental profiles of IPMNs to define multi-omic phenotypes. Using transfer learning, we projected IPMN-derived transcriptional programs onto spatial transcriptomic datasets from IPMNs and pancreatic intraepithelial neoplasias (PanINs). We identified two major phenotypes: one associated with cancer-associated fibroblasts and epithelial-to-mesenchymal transition, shared across IPMN, PanIN, and PDAC; and a second, glycolysis-enriched phenotype with a unique somatic mutation profile specific to IPMN. Spatial mapping further revealed grade-specific enrichment of transcriptional programs and distinct interactions with stromal and immune subtypes, underscoring the role of the precancer microenvironment in progression. These findings establish multi-omic phenotypes that unify genetic, transcriptional, and microenvironmental heterogeneity, providing a framework for distinguishing progressive from indolent precancers and a web-based public atlas for future exploration of these data and transcriptional phenotypes.<\/jats:p>","DOI":"10.1101\/2025.11.03.686234","type":"posted-content","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T16:25:20Z","timestamp":1762273520000},"source":"Crossref","is-referenced-by-count":1,"title":["Integrative analysis of genomic and transcriptomic data informs precancer progression in the 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