{"id":"doi:10.64898/2026.06.11.731518","kind":"preprint","title":"A multimodal foundation model linking histopathology and DNA methylation","authors":["Wang D","Zhang J","Chen C","Zhang W","Wang S","Meng Y","Sonpavde G","Horbinski C","Tian Y"],"author_count":9,"year":2026,"published":"2026-06-14","venue":"bioRxiv","cited_by":0,"doi":"10.64898/2026.06.11.731518","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.64898/2026.06.11.731518","archive_url":"https://space-kitty.com/papers/doi:10.64898/2026.06.11.731518","updated":null,"pmid":null,"pmcid":null,"openalex_id":null,"pdf_url":null,"abstract":"Hematoxylin and eosin (H&E) slides are routinely available in cancer care, but molecular profiling often requires additional tissue processing and turnaround time. We introduce HistoMethyl, a DNA methylation-aware pathology foundation model that aligns whole-slide histopathology with matched genome-scale methylation beta-value profiles during pre-training while requiring only an H&E slide at inference. We evaluated HistoMethyl across four task groups: gene mutation prediction, morphology-associated classification, overall survival prediction, and direct DNA methylation beta-value recovery. Evaluation spanned TCGA cross-validation, a disease-held-out lower-grade glioma cohort, and external cohort validation in CPTAC glioblastoma and SurGen rectal adenocarcinoma, totaling 14 cancer cohorts and 81 gene mutation tasks. The best-performing configuration improved mean mutation AUROC by 5.03 percentage points. By converting DNA methylation supervision into an H&E-only representation, His-toMethyl could support an early molecular triage layer that helps prioritize cases for confirmatory sequencing, methylation profiling, immunohistochemistry, and molecular tumor board review. These image-only predictions are intended to accelerate downstream molecular testing and tissue allocation while leaving final diagnosis and treatment selection anchored in validated molecular assays.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":false,"retracted":false,"peer_reviewed":false,"categories":[],"details":{"peer_reviewed":false,"note":"Preprint: not peer reviewed."},"provenance":"europepmc","attribution":"Abstract of \"A multimodal foundation model linking histopathology and DNA methylation\" by Wang D, Zhang J, Chen C et al., https://doi.org/10.64898/2026.06.11.731518, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"ai-medicine","name":"AI in Clinical Medicine","domain_slug":"medicine"}],"cited_in_dossiers":[]}