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Record W4409411157 · doi:10.1038/s41467-025-57636-6

A genetically informed brain atlas for enhancing brain imaging genomics

2025· article· en· W4409411157 on OpenAlexfundno aff
Jingxuan Bao, Junhao Wen, Changgee Chang, Shizhuo Mu, Jiong Chen, Manu Shivakumar, Yuhan Cui, Güray Erus, Zhijian Yang, Shu Yang, Zixuan Wen

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGene expression and cancer classification
Canadian institutionsnot available
FundersNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchGenentechIXICOH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationUniversity of Southern CaliforniaBiogenBioClinicaU.S. Department of DefenseMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeNovartis Pharmaceuticals CorporationPfizerEli Lilly and CompanyBristol-Myers SquibbNational Institute on AgingAlzheimer's AssociationNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsHeritabilityBiologyNeuroimagingBrain atlasGenomicsImaging geneticsGenetic architectureEvolutionary biologyEndophenotypeNeuroscienceComputational biologyQuantitative trait locusGeneticsGenomeCognitionGene

Abstract

fetched live from OpenAlex

Brain imaging genomics has manifested considerable potential in illuminating the genetic determinants of human brain structure and function. This has propelled us to develop the GIANT (Genetically Informed brAiN aTlas) that accounts for genetic and neuroanatomical variations simultaneously. Integrating voxel-wise heritability and spatial proximity, GIANT clusters brain voxels into genetically informed regions, while retaining fundamental anatomical knowledge. Compared to conventional (non-genetics) brain atlases, GIANT exhibits smaller intra-region variations and larger inter-region variations in terms of voxel-wise heritability. As a result, GIANT yields increased regional SNP heritability, enhanced polygenicity, and its polygenic risk score explains more brain volumetric variation than traditional neuroanatomical brain atlases. We provide extensive validation to GIANT and demonstrate its neuroanatomical validity, confirming its generalizability across populations with diverse genetic ancestries and various brain conditions. Furthermore, we present a comprehensive genetic architecture of the GIANT regions, covering their functional annotation at the molecular levels, their associations with other complex traits/diseases, and the genetic and phenotypic correlations among GIANT-defined imaging endophenotypes. In summary, GIANT constitutes a brain atlas that captures the complexity of genetic and neuroanatomical heterogeneity, thereby enhancing the discovery power and applicability of imaging genomics investigations in biomedical science.

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)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.010
Threshold uncertainty score0.035

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.003
Science and technology studies0.0010.001
Scholarly communication0.0020.001
Open science0.0010.002
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0100.003

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 head0.011
GPT teacher head0.326
Teacher spread0.315 · 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 designSimulation or modeling
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

Citations4
Published2025
Admission routes1
Has abstractyes

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