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UK Biobank imputation pipelines

About

Genotype imputation is a computational technique for estimating missing genotypes in SNP array data, using a reference panel of haplotypes. This approach extends to low-coverage whole genome sequencing data, aiding in filling missing genotypes or enhancing uncertain genotype calls from sequencing reads.

For both SNP array and low-coverage whole genome sequencing data, we've created two distinct pipelines using the UK Biobank reference panel (>200,000 samples; 700M variants) for genotype imputation. To ensure cost-effective implementation, we leverage efficient state-of-the-art tools, including IMPUTE5 (Rubinacci et al., 2020) for SNP array imputation and GLIMPSE2 (Rubinacci et al., 2023) for low-coverage WGS imputation.

Our pipelines can take input from a multi-sample VCF/BCF file with SNP array genotypes or a set of low-coverage BAM/CRAM files. Using the UK Biobank reference panel, the pipeline executes imputation through applets and dx command jobs, tailor-made for the UKB RAP. At the end of each imputation pipeline, a single multi-sample BCF file is generated per chromosome, encompassing genotype posteriors, dosages, and phased best-guess genotypes. Further outputs like haploid dosages can be acquired by specifying appropriate options in the imputation software.

Website and tutorials

Tutorials on how to use the pipelines can be found at:

https://srubinacci.gitbook.io/uk-biobank-imputation-pipelines/

Citation

If you use the pipelines in your research work, please cite the following papers:

Reference panel

Hofmeister RJ, Ribeiro DM, Rubinacci S, Delaneau O. 2023. Accurate rare variant phasing of whole-genome and whole-exome sequencing data in the UK Biobank. Nat Genet 55, 1243–1249 (2023).

Low-coverage WGS imputation

Rubinacci et al., Imputation of low-coverage sequencing data from 150,119 UK Biobank genomes. Nat Genet 55, 1088–1090 (2023).

SNP array imputation

Rubinacci et al., Genotype imputation using the Positional Burrows Wheeler Transform. PLoS Genet. 16, e1009049 (2020).

About the project

The UK Biobank imputation pipelines are developed by Simone Rubinacci & Olivier Delaneau.

License

The UK Biobank imputation pipelines are distributed with an MIT license.

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