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Record W3215996938 · doi:10.1038/s41467-021-27204-9

Atlas of RNA editing events affecting protein expression in aged and Alzheimer’s disease human brain tissue

2021· article· en· W3215996938 on OpenAlexaff
Yiyi Ma, Eric B. Dammer, Daniel Felsky, Duc M. Duong, Hans‐Ulrich Klein, Charles C. White, Maotian Zhou, Benjamin A. Logsdon, Cristin McCabe, Jishu Xu, Minghui Wang, Thomas S. Wingo, James J. Lah, Bin Zhang, Julie A. Schneider, Mariet Allen, Xue Wang, Nilüfer Ertekin‐Taner, Nicholas T. Seyfried, Allan I. Levey, David A. Bennett, Philip L. De Jager

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA regulation and disease
Canadian institutionsUniversity of TorontoCentre for Addiction and Mental Health
FundersNational Institute of Environmental Health SciencesNational Center for Research ResourcesNational Institute of Neurological Disorders and StrokeNational Institute on Drug AbuseNational Institute on AgingU.S. Department of Health and Human ServicesNational Institutes of HealthMayo Clinic
KeywordsAtlas (anatomy)Protein expressionHuman brainRNADiseaseBrain tissueHuman Protein AtlasComputational biologyNeuroscienceBiologyMedicineBioinformaticsPathologyGeneticsAnatomyGene

Abstract

fetched live from OpenAlex

RNA editing is a feature of RNA maturation resulting in the formation of transcripts whose sequence differs from the genome template. Brain RNA editing may be altered in Alzheimer's disease (AD). Here, we analyzed data from 1,865 brain samples covering 9 brain regions from 1,074 unrelated subjects on a transcriptome-wide scale to identify inter-regional differences in RNA editing. We expand the list of known brain editing events by identifying 58,761 previously unreported events. We note that only a small proportion of these editing events are found at the protein level in our proteome-wide validation effort. We also identified the occurrence of editing events associated with AD dementia, neuropathological measures and longitudinal cognitive decline in: SYT11, MCUR1, SOD2, ORAI2, HSDL2, PFKP, and GPRC5B. Thus, we present an extended reference set of brain RNA editing events, identify a subset that are found to be expressed at the protein level, and extend the narrative of transcriptomic perturbation in AD to RNA editing.

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)0.000
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0020.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

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 head0.019
GPT teacher head0.336
Teacher spread0.317 · 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

Citations61
Published2021
Admission routes1
Has abstractyes

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