Effect of predicted protein-truncating genetic variants on the human transcriptome
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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.
- Teacher spread
- 0.238 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
Accurate prediction of the functional effect of genetic variation is critical for clinical genome interpretation. We systematically characterized the transcriptome effects of protein-truncating variants, a class of variants expected to have profound effects on gene function, using data from the Genotype-Tissue Expression (GTEx) and Geuvadis projects. We quantitated tissue-specific and positional effects on nonsense-mediated transcript decay and present an improved predictive model for this decay. We directly measured the effect of variants both proximal and distal to splice junctions. Furthermore, we found that robustness to heterozygous gene inactivation is not due to dosage compensation. Our results illustrate the value of transcriptome data in the functional interpretation of genetic variants.
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.
The record
- Venue
- Science
- Topic
- Genomics and Chromatin Dynamics
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- —
- Funders
- U.S. National Library of MedicineNational Institute of General Medical SciencesNational Cancer InstituteNational Institute on Drug AbuseNational Institute of Diabetes and Digestive and Kidney DiseasesBiotechnology and Biological Sciences Research CouncilNatural Sciences and Engineering Research Council of CanadaSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNational Institutes of HealthNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteU.S. Department of DefenseLouis-Jeantet FoundationAcademy of FinlandH2020 European Research CouncilUniversity of OxfordNational Human Genome Research InstituteWellcome TrustWellcome
- Keywords
- BiologyGenetic variationGeneGeneticsTranscriptomeGene expressionExpression quantitative trait lociGenotypeRegulation of gene expressionProtein expressionPhenotypeSingle-nucleotide polymorphism
- Has abstract in OpenAlex
- yes