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Record W2988958689 · doi:10.1126/science.aay0793

Brain cell type–specific enhancer–promoter interactome maps and disease <b>-</b> risk association

2019· article· en· W2988958689 on OpenAlexafffund
Alexi Nott, Inge R. Holtman, Nicole G. Coufal, Johannes C. M. Schlachetzki, Miao Yu, Rong Hu, Claudia Z. Han, Monique Pena, Jiayang Xiao, Yin Wu, Zahara Keulen, Martina P. Pasillas, Carolyn O’Connor, Christian K. Nickl, Simon T. Schafer, Zeyang Shen, Robert A. Rissman, James B. Brewer, David Gosselin, David Gonda, Michael L. Levy, Michael G. Rosenfeld, Graham McVicker, Fred H. Gage, Bing Ren, Christopher K. Glass

Bibliographic record

VenueScience · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBioinformatics and Genomic Networks
Canadian institutionsCentre hospitalier de l'Université Laval
FundersNational Institute of Neurological Disorders and StrokeNational Institute of Diabetes and Digestive and Kidney DiseasesNational Cancer InstituteVeterans Affairs San Diego Healthcare SystemUniversity of California, San DiegoUniversitair Medisch Centrum GroningenCentre Hospitalier Universitaire de QuébecNational Center for Advancing Translational SciencesNederlandse Organisatie voor Wetenschappelijk OnderzoekNational Institutes of HealthRijksuniversiteit GroningenLudwig Institute for Cancer ResearchUniversité LavalU.S. Department of Veterans AffairsCancer Research InstituteJPB FoundationNational Institute on AgingAlzheimer's AssociationCure Alzheimer's Fund
KeywordsEnhancerInteractomeBiologyMicrogliaPhenotypePromoterGeneCell typeGeneticsGenetic associationComputational biologyCellGene expressionSingle-nucleotide polymorphismGenotypeImmunology

Abstract

fetched live from OpenAlex

Linking enhancers to disease Enhancers are genomic regions that regulate gene expression, sometimes in a cell-dependent manner. However, most of our knowledge of human brain cell–type enhancers derives from studies of bulk human brain tissue. Nott et al. examined chromatin and promoter activity in cell nuclei isolated from human brains. Genetic variants associated with brain traits and disease showed cell-specific patterns of enhancer enrichment. These data indicate that Alzheimer's disease is regulated by genetic variants within microglial cells, whereas psychiatric diseases tend to affect neurons. Science , this issue p. 1134

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)0.000
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: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.021

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0060.001

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 head0.003
GPT teacher head0.210
Teacher spread0.207 · 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

Citations793
Published2019
Admission routes2
Has abstractyes

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