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Record W2794167820 · doi:10.1073/pnas.1706100115

Susceptibility of brain atrophy to <i>TRIB3</i> in Alzheimer’s disease, evidence from functional prioritization in imaging genetics

2018· article· en· W2794167820 on OpenAlexfundno aff
Marco Lorenzi, André Altmann, Boris A. Gutman, Selina Wray, Charles Arber, Derrek P. Hibar, Neda Jahanshad, Jonathan M. Schott, Daniel C. Alexander, Paul M. Thompson, Sébastien Ourselin

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEndoplasmic Reticulum Stress and Disease
Canadian institutionsnot available
FundersNational Institute of Biomedical Imaging and BioengineeringNational Institute on AgingSeventh Framework ProgrammeMedical Research CouncilHorizon 2020 Framework ProgrammeNational Institutes of HealthAlzheimer’s Research UKEuropean CommissionBrain Research UKResearch Councils UKBrain Research TrustEngineering and Physical Sciences Research CouncilCanadian Institutes of Health ResearchNational Institute for Health and Care Research
KeywordsDiseasePrioritizationImaging geneticsAtrophyNeuroscienceAlzheimer's diseaseNeuroimagingMedicineBiologyPathology

Abstract

fetched live from OpenAlex

Significance In this study, we use an experimental imaging–genetics approach for investigating the genetic underpinnings of brain atrophy in Alzheimer’s disease. We successfully combined state-of-the-art imaging–genetics methods and experimental gene expression data to uncover biology in brain atrophy. The experimental paradigm highlighted a significant role of tribbles pseudokinase 3 ( TRIB3 ) in modulating the typical pattern of Alzheimer’s brain pathology. This result corroborates through rigorous data-driven statistical methods evidence emerging from previous studies about the role of TRIB3 in modulating known mechanisms of neurodegeneration, such as neuronal death, cellular homeostasis, and interaction with established genes causing autosomal dominant Alzheimer’s disease: APP and PSEN1 . The developed integrated statistical–experimental methodology could serve as a roadmap for investigations in other disorders.

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)0.005
metaresearch head score (Gemma)0.006
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.029

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0050.006
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.002
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.036
GPT teacher head0.316
Teacher spread0.280 · 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 designBench or experimental
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

Citations53
Published2018
Admission routes1
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicEndoplasmic Reticulum Stress and DiseaseFrench-language works237,207