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Record W3013862190 · doi:10.1038/s42003-020-0879-3

Analysis of mitochondrial m1A/G RNA modification reveals links to nuclear genetic variants and associated disease processes

2020· article· en· W3013862190 on OpenAlexfundno aff
Aminah T. Ali, Youssef Idaghdour, Alan Hodgkinson

Bibliographic record

VenueCommunications Biology · 2020
Typearticle
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
KeywordsMitochondrial DNAGeneticsMitochondrial diseaseBiologyRNAComputational biologyEvolutionary biologyGene

Abstract

fetched live from OpenAlex

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 or what impact it has on biological systems. Here, we quantify variation in m1A/G RNA modification levels at functionally important positions in the human mitochondrial genome across 11,552 samples from 39 tissue/cell types and find that modification levels are associated with mitochondrial transcript processing. We identify links between mitochondrial RNA modification levels and genetic variants in the nuclear genome, including a missense mutation in LONP1, and find that genetic variants within MRPP3 and TRMT61B are associated with RNA modification levels across a large number of tissues. Genetic variants linked to RNA modification levels are associated with multiple disease/disease-related phenotypes, including blood pressure, breast cancer and psoriasis, suggesting a role for mitochondrial RNA modification 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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation 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 score0.955
Threshold uncertainty score0.418

Codex and Gemma teacher scores by category

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

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 head0.039
GPT teacher head0.307
Teacher spread0.268 · 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 teacher head, 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

Citations38
Published2020
Admission routes1
Has abstractyes

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