Genotype imputation using the Positional Burrows Wheeler Transform.

PLoS Genetics
Simone RubinacciJonathan Marchini

Abstract

Genotype imputation is the process of predicting unobserved genotypes in a sample of individuals using a reference panel of haplotypes. In the last 10 years reference panels have increased in size by more than 100 fold. Increasing reference panel size improves accuracy of markers with low minor allele frequencies but poses ever increasing computational challenges for imputation methods. Here we present IMPUTE5, a genotype imputation method that can scale to reference panels with millions of samples. This method continues to refine the observation made in the IMPUTE2 method, that accuracy is optimized via use of a custom subset of haplotypes when imputing each individual. It achieves fast, accurate, and memory-efficient imputation by selecting haplotypes using the Positional Burrows Wheeler Transform (PBWT). By using the PBWT data structure at genotyped markers, IMPUTE5 identifies locally best matching haplotypes and long identical by state segments. The method then uses the selected haplotypes as conditioning states within the IMPUTE model. Using the HRC reference panel, which has ∼65,000 haplotypes, we show that IMPUTE5 is up to 30x faster than MINIMAC4 and up to 3x faster than BEAGLE5.1, and uses less memory than both these m...Continue Reading

References

Oct 19, 2007·Nature·UNKNOWN International HapMap ConsortiumJohn Stewart
Feb 12, 2009·Pharmacogenomics·Eleftheria Zeggini, John P A Ioannidis
Jun 3, 2010·Nature Reviews. Genetics·Jonathan Marchini, Bryan Howie
Mar 3, 2012·G3 : Genes - Genomes - Genetics·Bryan HowieMatthew Stephens
Dec 28, 2012·Nature Methods·Olivier DelaneauJonathan Marchini
Oct 4, 2015·Nature·UNKNOWN 1000 Genomes Project ConsortiumGonçalo R Abecasis
Jan 11, 2016·American Journal of Human Genetics·Brian L Browning, Sharon R Browning
May 6, 2016·PLoS Computational Biology·Jerome KelleherGilean McVean
Aug 23, 2016·Nature Genetics·Shane McCarthyUNKNOWN Haplotype Reference Consortium
Aug 30, 2016·Nature Genetics·Sayantan DasChristian Fuchsberger
Oct 28, 2016·Nature Genetics·Po-Ru LohAlkes L Price
Oct 28, 2017·Nature Genetics·Jennifer A BrodyL Adrienne Cupples
Aug 14, 2018·American Journal of Human Genetics·Brian L BrowningSharon R Browning
Oct 12, 2018·Nature·Clare BycroftJonathan Marchini
Nov 30, 2019·Nature Communications·Olivier DelaneauEmmanouil T Dermitzakis

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Citations

Apr 7, 2021·Nature Genetics·Sahin NaqviPeter Claes
Sep 4, 2021·American Journal of Human Genetics·Brian L BrowningSharon R Browning
Oct 12, 2021·Frontiers in Genetics·Katharina StahlInke R König
Oct 19, 2021·Nature·Joshua D BackmanManuel A R Ferreira

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Methods Mentioned

BETA
chip
genotyping

Software Mentioned

MINIMAC4
IMPUTE5
MINIMAC
bgenix
m3vcf
MSPRIME
Omics for Precision Medicine ( TOPMed )
IMPUTE
cat
imp5

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