Software & Tools

GLIMPSE2 is a state-of-the-art software in low-coverage WGS imputation. It scales sublinearly to reference panels containing millions of haplotypes and with millions of rare variants. Achieves highly accurate genotype calls even at rare variants (MAF < 0.1%) and ultra-low sequencing coverages (0.1× to 0.5×).

Applied to impute the UK Biobank's 150,119-genome WGS release, using a reference panel of 280,238 haplotypes and over 580 million markers. Compute cost: under $0.1 per genome. Also handles ancient DNA genotyping from degraded low-coverage samples.

SHAPEIT5 is a haplotype phasing method for large WGS datasets. Applied to the complete UK Biobank WGS and WES data, it phases rare variants with switch error rates below 5% even for variants found in a single individual among 100,000 — achiving non-random phasing of singletons without family information. The phased UK Biobank reference panel built with SHAPEIT5 also improved downstream imputation accuracy.

IMPUTE5 is a genotype imputation method built for reference panels with millions of samples. Using the Positional Burrows-Wheeler Transform (PBWT), it identifies optimal subsets of reference haplotypes per individual. Computational cost increases only marginally as reference panel size grows.