An efficient algorithm for the extraction of HGVS variant descriptions from sequences

Vis, Jonathan K.; Vermaat, Martijn; Taschner, Peter E.M.; Kok, Joost N.; Laros, Jeroen F. J.

doi:10.1093/bioinformatics/btv443

Cited by 28 publications

(21 citation statements)

References 11 publications

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“…Allelic sequences of PKD1 and PKD2 were aligned to the human reference genome GRCh37.p13 using BLASR (Chaisson & Tesler, ), and reporting a single best‐scoring alignment. Variants were extracted by comparison between the reconstructed alleles and the human reference sequence with the Variant Description Extractor from the Mutalyzer Suite 2.0.21 (Vis, Vermaat, Taschner, Kok, & Laros, ).…”

Section: Methodsmentioning

confidence: 99%

DetectingPKD1variants in polycystic kidney disease patients by single-molecule long-read sequencing

et al. 2017

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A genetic diagnosis of autosomal‐dominant polycystic kidney disease (ADPKD) is challenging due to allelic heterogeneity, high GC content, and homology of the PKD1 gene with six pseudogenes. Short‐read next‐generation sequencing approaches, such as whole‐genome sequencing and whole‐exome sequencing, often fail at reliably characterizing complex regions such as PKD1. However, long‐read single‐molecule sequencing has been shown to be an alternative strategy that could overcome PKD1 complexities and discriminate between homologous regions of PKD1 and its pseudogenes. In this study, we present the increased power of resolution for complex regions using long‐read sequencing to characterize a cohort of 19 patients with ADPKD. Our approach provided high sensitivity in identifying PKD1 pathogenic variants, diagnosing 94.7% of the patients. We show that reliable screening of ADPKD patients in a single test without interference of PKD1 homologous sequences, commonly introduced by residual amplification of PKD1 pseudogenes, by direct long‐read sequencing is now possible. This strategy can be implemented in diagnostics and is highly suitable to sequence and resolve complex genomic regions that are of clinical relevance.

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Section: Methodsmentioning

confidence: 99%

DetectingPKD1variants in polycystic kidney disease patients by single-molecule long-read sequencing

et al. 2017

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“…A recent addition to the Mutalyzer tool suite is the HGVS variant Description Extractor [19]. This tool automatically generates HGVS variant descriptions given a reference sequence and an observed sequence.…”

Section: Description Extractormentioning

confidence: 99%

Mutalyzer 2: Next Generation HGVS Nomenclature Checker

Lefter

Vis

Vermaat

et al. 2020

Preprint

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Unambiguous variant descriptions are of utmost importance in clinical genetic diagnostics, scientific literature, and genetic databases. The Human Genome Variation Society (HGVS) publishes a comprehensive set of guidelines on how variants should be correctly and unambiguously described. We present the implementation of the Mutalyzer 2 tool suite, designed to automatically apply the HGVS guidelines so users do not have to deal with the HGVS intricacies explicitly to check and correct their variant descriptions. Mutalyzer is profusely used by the community, having processed over 133 million descriptions since its launch. Over a five year period, Mutalyzer reported a correct input in approximately 50% of cases. In 41% of the cases either a syntactic or semantic error was identified and for approximately 7% of cases, Mutalyzer was able to automatically correct the description.

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“…For each locus of interest, FASTA format sequences were generated for each allele of each individual by applying the variants in each locus to the reference sequence by using Mutalyzer. 42,43 The VCF files were then used to create a coverage track in BED format for each individual for each locus of interest. A haplotype quality of at least 20 is required to be considered "covered."…”

Section: Variant Callingmentioning

confidence: 99%

Repurposing of Diagnostic Whole Exome Sequencing Data of 1,583 Individuals for Clinical Pharmacogenetics

Lee

Allard

Bollen

et al. 2019

Clin Pharma and Therapeutics

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For ~ 80 drugs, widely recognized pharmacogenetics dosing guidelines are available. However, the use of these guidelines in clinical practice remains limited as only a fraction of patients is subjected to pharmacogenetic screening. We investigated the feasibility of repurposing whole exome sequencing (WES) data for a panel of 42 variants in 11 pharmacogenes to provide a pharmacogenomic profile. Existing diagnostic WES‐data from child‐parent trios totaling 1,583 individuals were used. Results were successfully extracted for 39 variants. No information could be extracted for three variants, located in CYP2C19, UGT1A1, and CYP3A5, and for CYP2D6 copy number. At least one actionable phenotype was present in 86% of the individuals. Haplotype phasing proved relevant for CYP2B6 assignments as 1.5% of the phenotypes were corrected after phasing. In conclusion, repurposing WES‐data can yield meaningful pharmacogenetic profiles for 7 of 11 important pharmacogenes, which can be used to guide drug treatment.

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An efficient algorithm for the extraction of HGVS variant descriptions from sequences

Abstract: j.k.vis@lumc.nl.

Cited by 28 publications

References 11 publications

DetectingPKD1variants in polycystic kidney disease patients by single-molecule long-read sequencing

DetectingPKD1variants in polycystic kidney disease patients by single-molecule long-read sequencing

Mutalyzer 2: Next Generation HGVS Nomenclature Checker

Repurposing of Diagnostic Whole Exome Sequencing Data of 1,583 Individuals for Clinical Pharmacogenetics

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