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Record W2948545994 · doi:10.1101/666339

Nuclear genetic regulation of human mitochondrial RNA modification

2019· preprint· en· W2948545994 on OpenAlexfundno aff
Aminah T. Ali, Youssef Idaghdour, Alan Hodgkinson

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2019
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA modifications and cancer
Canadian institutionsnot available
FundersCommon FundNational Cancer InstituteNational Institute of Mental HealthNew York University Abu DhabiNational Heart, Lung, and Blood InstituteMedical Research CouncilNational Institutes of HealthStanford Bio-XUniversité de GenèveKing's College LondonNational Institute for Health and Care ResearchEuropean CommissionBroad InstituteUniversity of PennsylvaniaNational Institute on Drug AbuseUniversity of MiamiYork UniversityNational Human Genome Research InstituteWellcome TrustNorth Carolina State UniversityUniversity of ChicagoHarvard UniversityNIH Office of the DirectorVan Andel Research InstituteNational Institute of Neurological Disorders and StrokeLeidos
KeywordsBiologyMissense mutationRNAMitochondrial DNAGeneticsPhenotypeMitochondrionGenomeMitochondrial diseaseGene

Abstract

fetched live from OpenAlex

Abstract RNA modifications affect the stability and function of RNA species, regulating important downstream processes. Modification levels are often dynamic, varying between tissues and individuals, although it is not always clear what modulates this variation or what impact it has on biological systems. Here, we quantify variation in RNA modification levels at functionally important positions in the mitochondrial genome across 11,552 samples from 39 tissue/cell types and find evidence that modification levels impact mitochondrial transcript processing. We identify novel links between mitochondrial RNA modification levels in whole blood and genetic variants in the nuclear genome, including missense mutations in LONP1 and PNPT1 , as well as missense mutations in MRPP3 , SLC25A26 and MTPAP that associate with RNA modification levels across multiple tissue types. Genetic variants linked to modification levels are associated with multiple disease phenotypes, including blood pressure, breast cancer and Moyamoya disease, suggesting a role for these processes in complex 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)0.000
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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

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

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 head0.014
GPT teacher head0.235
Teacher spread0.220 · 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

Citations1
Published2019
Admission routes1
Has abstractyes

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