ArticleNature. Mental health2026
Multi-organ AI endophenotypes chart the heterogeneity of brain, eye and heart pan-disease.
Article in Nature. Mental health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Article
- Integrating Artificial Intelligence with Global Genomic Resources: A Narrative Review of Implications for Precision Medicine.Journal of multidisciplinary healthcare · 2026Review
- MegaEye: Applying multiple machine learning approaches to identify oral compounds with ocular bioactivity.Artificial intelligence in the life sciences · 2025Article
- Sleep chart of biological aging clocks across organs and omics.medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Disease heterogeneity and commonality pose significant challenges to precision medicine, as traditional approaches frequently focus on single disease entities and overlook shared mechanisms across conditions. Inspired by pan-cancer and multi-organ research, 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, curated from the MULTI consortium, we applied a weakly-supervised deep learning model (Surreal-GAN) 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 (Eye 1-3), and heart (Heart 1-2), respectively. We found Brain 3 to be a risk factor for Alzheimer's disease (AD) progression and mortality, whereas Brain 5 was protective against AD progression. Crucially, in data from an anti-amyloid AD drug (solanezumab), heterogeneity in cognitive decline trajectories was observed across treatment groups. At week 240, patients with lower brain 1-3 expression had slower cognitive decline, whereas patients with higher expression had faster cognitive decline. A multi-layer causal pathway pinpointed Brain 1 as a mediational endophenotype linking the FLRT2 protein to migraine, exemplifying novel therapeutic targets and pathways. Additionally, genes associated with Eye 1 and Eye 3 were enriched in cancer drug-related gene sets with causal links to specific cancer types and proteins. Finally, Heart 1 and Heart 2 had the highest mortality risk and unique medication history profiles, with Heart 1 showing favorable responses to antihypertensive medications and Heart 2 to digoxin treatment. The 11 MAEs provide novel AI dimensional representations for precision medicine and highlight the potential of AI-driven patient stratification for disease risk monitoring, clinical trials, and drug discovery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.