Dekeyser, T.; Génin, E.; Herzig, A.F. Opening the Black Box of Imputation Software to Study the Impact of Reference Panel Composition on Performance. Genes2023, 14, 410.
Dekeyser, T.; Génin, E.; Herzig, A.F. Opening the Black Box of Imputation Software to Study the Impact of Reference Panel Composition on Performance. Genes 2023, 14, 410.
Dekeyser, T.; Génin, E.; Herzig, A.F. Opening the Black Box of Imputation Software to Study the Impact of Reference Panel Composition on Performance. Genes2023, 14, 410.
Dekeyser, T.; Génin, E.; Herzig, A.F. Opening the Black Box of Imputation Software to Study the Impact of Reference Panel Composition on Performance. Genes 2023, 14, 410.
Abstract
Genotype imputation is widely used to enrich genetic datasets. The operation relies of panels of known reference haplotypes with typically whole-genome sequencing data. How to choose a reference panel has been widely studied and it is essential to have a panel that is well matched to the individuals who require imputation of missing genotypes. However, it is broadly accepted that such an imputation panel will have an enhanced performance with the inclusion of diversity; haplotypes from many different populations. We investigate this observation in this work by examining in fine detail exactly which reference haplotypes are contributing at different regions of the genome. This is achieved using a novel method of inserting synthetic genetic variation into the reference panel in order to track the performance of leading imputation algorithms. We show that while diversity may globally improve imputation accuracy, there can be occasions where incorrect genotypes are imputed following the inclusion of more diverse haplotypes in the reference panel. We however demonstrate a technique for retaining and benefitting from the diversity in the reference panel whilst avoiding the occasional adverse effects on imputation accuracy. What is more, our results elucidate more clearly the role of the diversity in a reference panel than has been shown in previous studies.
Keywords
genotype imputation; population genetics; rare-variants; reference panel; admixture
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
