webGQT: A Shiny Server for Genotype Query Tools for Model-Based Variant Filtering

Software to call single-nucleotide polymorphisms or related genetic variants has converged on the variant call format (VCF) as the output format of choice. This has created a need for tools to work with VCF files. While an increasing number of software exists to read VCF data, many only extract the genotypes without including the data associated with each genotype that describes its quality. We created the r package vcfr to address this issue. We developed a VCF file exploration tool implemented in the r language because r provides an interactive experience and an environment that is commonly used for genetic data analysis. Functions to read and write VCF files into r as well as functions to extract portions of the data and to plot summary statistics of the data are implemented. vcfr further provides the ability to visualize how various parameterizations of the data affect the results. Additional tools are included to integrate sequence (fasta) and annotation data (GFF) for visualization of genomic regions such as chromosomes. Conversion functions translate data from the vcfr data structure to formats used by other r genetics packages. Computationally intensive functions are implemented in C++ to improve performance. Use of these tools is intended to facilitate VCF data exploration, including intuitive methods for data quality control and easy export to other r packages for further analysis. vcfr thus provides essential, novel tools currently not available in r.

Genotype Query Tools (GQT) is a new indexing strategy that expedites analyses of genome variation datasets in VCF format based on sample genotypes, phenotypes and relationships. GQT’s compressed genotype index minimizes decompression for analysis, and performance relative to existing methods improves with cohort size. We show substantial (up to 443 fold) performance gains over existing methods and demonstrate GQT’s utility for exploring massive datasets involving thousands to millions of genomes.

The UK’s 100,000 Genomes Project has the aim of sequencing 100,000 genomes from UK National Health Service (NHS) patients while concomitantly transforming clinical care such that whole genome sequencing becomes routine clinical practice in the UK. Policymakers claim that the project will revolutionize NHS care. We wished to explore the 100,000 Genomes Project, and in particular, the extent to which policymaker claims have helped or hindered the work of those associated with Genomics England – the company established by the Department of Health to deliver the project. We interviewed 20 individuals linked to, or working for Genomics England. Interviewees had double-edged views about the context within which they were working. On the one hand, policymakers’ expectations attached to the venture were considered vacuous “genohype”; on the other hand, they were considered the impetus needed for those trying to advance genomic research into clinical practice. Findings should be considered for future genomes projects.