ArticleGenetics in medicine : official journal of the American College of Medical Genetics2018
Catching hidden variation: systematic correction of reference minor allele annotation in clinical variant calling.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Pangenome analysis of nine soybean cyst nematode genomes reveals hidden variation contributing to diversity and adaptation.BMC genomics · 2026Article
- Mango pangenome reveals dramatic impacts of reference bias on population genomic analyses.Horticulture research · 2025Article
- Bioinformatics of germline variant discovery for rare disease diagnostics: current approaches and remaining challenges.Briefings in bioinformatics · 2024Review
- Human Exome Sequencing and Prospects for Predictive Medicine: Analysis of International Data and Own Experience.Journal of personalized medicine · 2023Review
- Haplotype sequence collection of ABO blood group alleles by long-read sequencing reveals putative A1-diagnostic variants.Blood advances · 2023Article
- Quality control of large genome datasets.HGG advances · 2022Article
- Pan-human consensus genome significantly improves the accuracy of RNA-seq analyses.Genome research · 2022Article
- Systematic benchmark of state-of-the-art variant calling pipelines identifies major factors affecting accuracy of coding sequence variant discovery.BMC genomics · 2022Article
- Testing assembly strategies of Francisella tularensis genomes to infer an evolutionary conservation analysis of genomic structures.BMC genomics · 2021Article
- Assembly and annotation of an Ashkenazi human reference genome.Genome biology · 2020Article
- Whole‑exome sequencing in Russian children with non‑type 1 diabetes mellitus reveals a wide spectrum of genetic variants in MODY‑related and unrelated genes.Molecular medicine reports · 2019Article
- Whole-exome sequencing provides insights into monogenic disease prevalence in Northwest Russia.Molecular genetics & genomic medicine · 2019Article
- Is it time to change the reference genome?Genome biology · 2019Article
- Opening up new horizons for psychiatric genetics in the Russian Federation: moving toward a national consortium.Molecular psychiatry · 2019Article
- hg19KIndel: ethnicity normalized human reference genome.BMC genomics · 2019Article
- Article
- De novo human genome assemblies reveal spectrum of alternative haplotypes in diverse populations.Nature communications · 2018Article
- Interpretation of genomic sequencing: variants should be considered uncertain until proven guilty.Genetics in medicine : official journal of the American College of Medical Genetics · 2018Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PurposeWe comprehensively assessed the influence of reference minor alleles (RMAs), one of the inherent problems of the human reference genome sequence.MethodsThe variant call format (VCF) files provided by the 1000 Genomes and Exome Aggregation Consortium (ExAC) consortia were used to identify RMA sites. All coding RMA sites were checked for concordance with UniProt and the presence of same codon variants. RMA-corrected predictions of functional effect were obtained with SIFT, PolyPhen-2, and PROVEAN standalone tools and compared with dbNSFP v2.9 for consistency.ResultsWe systematically characterized the problem of RMAs and identified several possible ways in which RMA could interfere with accurate variant discovery and annotation. We have discovered a systematic bias in the automated variant effect prediction at the RMA loci, as well as widespread switching of functional consequences for variants located in the same codon as the RMA. As a convenient way to address the problem of RMAs we have developed a simple bioinformatic tool that identifies variation at RMA sites and provides correct annotations for all such substitutions. The tool is available free of charge at http://rmahunter.bioinf.me.ConclusionCorrection of RMA annotation enhances the accuracy of next-generation sequencing-based methods in clinical practice.
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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.