ArticleGenome medicine2014
Choice of transcripts and software has a large effect on variant annotation.
Article in Genome medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 2 of them syntheses that pooled it.
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Who cites it
116 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Transformers meets neoantigen detection: a systematic literature review.Journal of integrative bioinformatics · 2024Pooled it
- A Systematic Literature Review of Whole Exome and Genome Sequencing Population Studies of Genetic Susceptibility to Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Pooled it
- Model Context Protocol: The unexpected catalyst of a bioinformatics interoperability revolution.PLoS computational biology · 2026Article
- A Comprehensive Analysis of the Agreement and Performance of Variant Annotation Programs in Equine Genomes.Genes · 2026Article
- SNPWay: streamlined SNP-to-function and pathway over-representation analysis.bioRxiv : the preprint server for biology · 2026Article
- From SNPs to pathways: a genome-wide benchmark of annotation discrepancies and their impact on protein- and pathway-level inference.BMC genomics · 2026Article
- From SNPs to Pathways: A genome-wide benchmark of annotation discrepancies and their impact on protein- and pathway-level inference.bioRxiv : the preprint server for biology · 2026Article
- Mapping rare protein-coding variants on multi-organ imaging traits.Nature communications · 2025Article
- Genome annotations matter: characterizing Ensembl hg38 annotations from 2014 to 2023.BMC genomics · 2025Article
- To be or not to be a protein coding mutation, that's the question!NAR genomics and bioinformatics · 2025Review
- The promises and pitfalls of automated variant interpretation: a comprehensive review.Briefings in bioinformatics · 2025Review
- Pathway polygenic risk scores (pPRS) for the analysis of gene-environment interaction.PLoS genetics · 2025Article
- Toward streamline variant classification: discrepancies in variant nomenclature and syntax for ClinVar pathogenic variants across annotation tools.Human genomics · 2025Article
- PathVar: A Customisable NGS Variant Calling Algorithm Implicates Novel Candidate Genes and Pathways in Hemiplegic Migraine.Clinical genetics · 2025Article
- VAREANT: a bioinformatics application for gene variant reduction and annotation.Bioinformatics advances · 2025Article
- Genome-wide functional annotation of variants: a systematic review of state-of-the-art tools, techniques and resources.Frontiers in pharmacology · 2025Review
- Best practices for germline variant and DNA methylation analysis of second- and third-generation sequencing data.Human genomics · 2024Review
- Review
- A loss-of-function variant in ZCWPW1 causes human male infertility with sperm head defect and high DNA fragmentation.Reproductive health · 2024Article
- Bioinformatics of germline variant discovery for rare disease diagnostics: current approaches and remaining challenges.Briefings in bioinformatics · 2024Review
56 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
backgroundVariant annotation is a crucial step in the analysis of genome sequencing data. Functional annotation results can have a strong influence on the ultimate conclusions of disease studies. Incorrect or incomplete annotations can cause researchers both to overlook potentially disease-relevant DNA variants and to dilute interesting variants in a pool of false positives. Researchers are aware of these issues in general, but the extent of the dependency of final results on the choice of transcripts and software used for annotation has not been quantified in detail.
methodsThis paper quantifies the extent of differences in annotation of 80 million variants from a whole-genome sequencing study. We compare results using the RefSeq and Ensembl transcript sets as the basis for variant annotation with the software Annovar, and also compare the results from two annotation software packages, Annovar and VEP (Ensembl's Variant Effect Predictor), when using Ensembl transcripts.
resultsWe found only 44% agreement in annotations for putative loss-of-function variants when using the RefSeq and Ensembl transcript sets as the basis for annotation with Annovar. The rate of matching annotations for loss-of-function and nonsynonymous variants combined was 79% and for all exonic variants it was 83%. When comparing results from Annovar and VEP using Ensembl transcripts, matching annotations were seen for only 65% of loss-of-function variants and 87% of all exonic variants, with splicing variants revealed as the category with the greatest discrepancy. Using these comparisons, we characterised the types of apparent errors made by Annovar and VEP and discuss their impact on the analysis of DNA variants in genome sequencing studies.
conclusionsVariant annotation is not yet a solved problem. Choice of transcript set can have a large effect on the ultimate variant annotations obtained in a whole-genome sequencing study. Choice of annotation software can also have a substantial effect. The annotation step in the analysis of a genome sequencing study must therefore be considered carefully, and a conscious choice made as to which transcript set and software are used for annotation.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.