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Record W4414623171 · doi:10.1038/s41551-025-01506-5

Brain–heart–eye axis revealed by multi-organ imaging genetics and proteomics

2025· article· en· W4414623171 on OpenAlexaff
Andrew Zalesky, Ye Tian, Luigi Ferrucci, Wenjia Bai, Michael S. Rafii, Paul Aisen, Jian Zeng, Aleix Boquet-Pujadas, Filippos Anagnostakis, Michael R. Duggan, Cassandra M Joynes, Arthur W. Toga, Zhijian Yang, Keenan A. Walker, Christos Davatzikos, Junhao Wen

Bibliographic record

VenueNature Biomedical Engineering · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsArtificial Intelligence in Medicine (Canada)
FundersNational Institute on Aging
KeywordsProteomicsRepurposingDiseasePhenotypeDrug repositioningHuman diseaseSelection (genetic algorithm)Human geneticsEpistasis

Abstract

fetched live from OpenAlex

Multi-organ research investigates interconnections among multiple human organ systems, enhancing our understanding of human aging and disease mechanisms. Here we use multi-organ imaging, individual- and summary-level genetics, and proteomics data consolidated via the MULTI Consortium to delineate a brain-heart-eye axis using brain patterns of structural covariance (PSCs), heart imaging-derived phenotypes (IDPs) and eye IDPs. We find that proteome-wide associations of the PSCs and IDPs show within-organ specificity and cross-organ interconnections. Pleiotropic effects of common single-nucleotide polymorphisms are observed across multiple organs, and key genetic parameters are estimated for single-nucleotide polymorphism-based heritability, polygenicity and selection signatures across the three organs. A gene-drug-disease network shows the potential of drug repurposing for cross-organ diseases. Co-localization and causal analyses reveal cross-organ causal relationships between PSC/IDP and chronic diseases, such as Alzheimer's disease, heart failure and glaucoma. Finally, integrating multi-organ/omics features improves prediction for systemic disease categories and cognition compared with single-organ/omics features, providing future avenues for modelling human aging and disease.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0020.001
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.002
GPT teacher head0.247
Teacher spread0.245 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations6
Published2025
Admission routes1
Has abstractyes

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