biostudies-literatureUnknownMULTI consortiumNIA NIH HHSDisease heterogeneity and commonality pose significant challenges to precision medicine, as traditional approaches frequently focus on single disease entities and overlook shared mechanisms across conditions¹. Inspired by pan-cancer² and multi-organ research³, we introduce the concept of "pan-disease" to investigate the heterogeneity and shared etiology in brain, eye, and heart diseases. Leveraging individual-level data from 129,340 participants, as well as summary-level data from the MULTI consortium, we applied a weakly-supervised deep learning model (Surreal-GAN^4,5) to multi-organ imaging, genetic, proteomic, and RNA-seq data, identifying 11 AI-derived biomarkers - called Multi-organ AI Endophenotypes (MAEs) - for the brain (Brain 1-6), eye (EmedRxiv : the preprint server for health sciences2025.08.09.25333350https://www.ebi.ac.uk/biostudies/studies/S-EPMC12363687biostudies-literatureMulti-organ AI Endophenotypes Chart the Heterogeneity of Pan-disease in the Brain, Eye, and Heart.PMC12363687RF1 AG092412RF1 AG054409Zalesky ADuggan MRErus GTian YESrinivasan DBai WWalker KAAnagnostakis FBoquet-Pujadas AYang ZDavatzikos CWen JJoynes CMPatel PJMULTI consortiumfalseMulti-organ AI Endophenotypes Chart the Heterogeneity of Pan-disease in the Brain, Eye, and Heart.Disease heterogeneity and commonality pose significant challenges to precision medicine, as traditional approaches frequently focus on single disease entities and overlook shared mechanisms across conditions¹. Inspired by pan-cancer² and multi-organ research³, we introduce the concept of "pan-disease" to investigate the heterogeneity and shared etiology in brain, eye, and heart diseases. Leveraging individual-level data from 129,340 participants, as well as summary-level data from the MULTI consortium, we applied a weakly-supervised deep learning model (Surreal-GAN^4,5) to multi-organ imaging, genetic, proteomic, and RNA-seq data, identifying 11 AI-derived biomarkers - called Multi-organ AI Endophenotypes (MAEs) - for the brain (Brain 1-6), eye (E2025-01-01T00:00:00Z2025 Aug2026-06-19T03:16:49.51Z2026-06-19T03:07:39.208ZS-EPMC123636874083243210.1101/2025.08.09.25333350