Short-read aligner performance in germline variant identification

Wilton, Richard; Szalay, Alexander S

doi:10.1093/bioinformatics/btad480

Cited by 3 publications

References 54 publications

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Bioinformatics of germline variant discovery for rare disease diagnostics: current approaches and remaining challenges

Barbitoff,

Ushakov,

Lazareva

et al. 2024

Briefings in Bioinformatics

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Next-generation sequencing (NGS) has revolutionized the field of rare disease diagnostics. Whole exome and whole genome sequencing are now routinely used for diagnostic purposes; however, the overall diagnosis rate remains lower than expected. In this work, we review current approaches used for calling and interpretation of germline genetic variants in the human genome, and discuss the most important challenges that persist in the bioinformatic analysis of NGS data in medical genetics. We describe and attempt to quantitatively assess the remaining problems, such as the quality of the reference genome sequence, reproducible coverage biases, or variant calling accuracy in complex regions of the genome. We also discuss the prospects of switching to the complete human genome assembly or the human pan-genome and important caveats associated with such a switch. We touch on arguably the hardest problem of NGS data analysis for medical genomics, namely, the annotation of genetic variants and their subsequent interpretation. We highlight the most challenging aspects of annotation and prioritization of both coding and non-coding variants. Finally, we demonstrate the persistent prevalence of pathogenic variants in the coding genome, and outline research directions that may enhance the efficiency of NGS-based disease diagnostics.

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Bioinformatics of germline variant discovery for rare disease diagnostics: current approaches and remaining challenges

Barbitoff,

Ushakov,

Lazareva

et al. 2024

Briefings in Bioinformatics

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Use of the “quick brown fox jumps over the lazy dog” pangram in academic papers

Teixeira da Silva

2024

Journal of Electrical Systems and Inf Technol

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In the English language, when a sentence contains all letters of the alphabet, such as “The/A quick brown fox jumps over the lazy dog”, this is known as a pangram. Curiously, despite its odd meaning, this fox-dog pangram has found practical usage in some applications, mainly in text typography related to computer graphics, in linguistics, as a writing tutorial, or for testing computer keyboards. Even more curiously, it has been detected as a residual of template text in some academic papers. This unique linguistic curiosity was examined by screening Scopus and Web of Science, as well as Google Scholar from 2019–2023, to appreciate its practical use, as well as to assess whether there were any cases of residual template text, the main target of this exercise. In the latter case, this letter advocates for the removal of this residual text, in the form of a literary correction.

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Development and validation of a minimal SNP genotyping panel for the differentiation of Cannabis sativa chemovars

Cull,

Joly

2024

Preprint

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Background Due to its previously illicit nature, cannabis had not fully reaped the benefits of recent innovations in genomic plant science. However, Canada’s legalization of cannabis in 2018 triggered significant new demand for robust genotyping tools to assist breeders in meeting consumer demands. While most molecular marker-based research on cannabis has focused on screening for traits of agronomic value, more recent research has sought to use molecular markers to differentiate between cannabis cultivars. Results In this study, we have conducted whole genome sequencing of 32 cannabis chemovars, mined the sequencing data for SNPs, developed a reduced SNP genotyping panel to discriminate between sequenced chemovars, then validated the 20-SNP panel using DNA from the sequenced varieties and tested the assays on commercially available cannabis products. The assay conversion rate was high in DNA extracted from fresh plant material and middling in DNA extracted from commercial samples. However, called genotypes were internally consistent, highlighting discrepancies between genotypes predicted using sequencing data and observed using genotyping assays. The primary contributions of this work are to clearly document the process used to develop this genotyping panel and outline improvements and goals for future iterations of PCR-based, minimal SNP panels to enable efficient development genotyping tools to identify and screen cannabis varieties. Conclusions Our key recommendations are to leverage higher read length paired-end short-read technology; conduct in-depth pre- and post-processing of reads, mapping, and variant calling data; integrate trait-associated loci to develop multi-purpose panels; use iterative approaches for in vitro validation; and integrate redundancy to account for errors throughout the pipeline and the effects of irradiation sterilization on cannabis DNA extracted from commercially available dried flower samples.

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Short-read aligner performance in germline variant identification

Cited by 3 publications

References 54 publications

Bioinformatics of germline variant discovery for rare disease diagnostics: current approaches and remaining challenges

Bioinformatics of germline variant discovery for rare disease diagnostics: current approaches and remaining challenges

Use of the “quick brown fox jumps over the lazy dog” pangram in academic papers

Development and validation of a minimal SNP genotyping panel for the differentiation of Cannabis sativa chemovars

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