Cargando…
Efficiency and Power as a Function of Sequence Coverage, SNP Array Density, and Imputation
High coverage whole genome sequencing provides near complete information about genetic variation. However, other technologies can be more efficient in some settings by (a) reducing redundant coverage within samples and (b) exploiting patterns of genetic variation across samples. To characterize as m...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395607/ https://www.ncbi.nlm.nih.gov/pubmed/22807667 http://dx.doi.org/10.1371/journal.pcbi.1002604 |
_version_ | 1782238000124526592 |
---|---|
author | Flannick, Jason Korn, Joshua M. Fontanillas, Pierre Grant, George B. Banks, Eric Depristo, Mark A. Altshuler, David |
author_facet | Flannick, Jason Korn, Joshua M. Fontanillas, Pierre Grant, George B. Banks, Eric Depristo, Mark A. Altshuler, David |
author_sort | Flannick, Jason |
collection | PubMed |
description | High coverage whole genome sequencing provides near complete information about genetic variation. However, other technologies can be more efficient in some settings by (a) reducing redundant coverage within samples and (b) exploiting patterns of genetic variation across samples. To characterize as many samples as possible, many genetic studies therefore employ lower coverage sequencing or SNP array genotyping coupled to statistical imputation. To compare these approaches individually and in conjunction, we developed a statistical framework to estimate genotypes jointly from sequence reads, array intensities, and imputation. In European samples, we find similar sensitivity (89%) and specificity (99.6%) from imputation with either 1× sequencing or 1 M SNP arrays. Sensitivity is increased, particularly for low-frequency polymorphisms ([Image: see text]), when low coverage sequence reads are added to dense genome-wide SNP arrays — the converse, however, is not true. At sites where sequence reads and array intensities produce different sample genotypes, joint analysis reduces genotype errors and identifies novel error modes. Our joint framework informs the use of next-generation sequencing in genome wide association studies and supports development of improved methods for genotype calling. |
format | Online Article Text |
id | pubmed-3395607 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33956072012-07-17 Efficiency and Power as a Function of Sequence Coverage, SNP Array Density, and Imputation Flannick, Jason Korn, Joshua M. Fontanillas, Pierre Grant, George B. Banks, Eric Depristo, Mark A. Altshuler, David PLoS Comput Biol Research Article High coverage whole genome sequencing provides near complete information about genetic variation. However, other technologies can be more efficient in some settings by (a) reducing redundant coverage within samples and (b) exploiting patterns of genetic variation across samples. To characterize as many samples as possible, many genetic studies therefore employ lower coverage sequencing or SNP array genotyping coupled to statistical imputation. To compare these approaches individually and in conjunction, we developed a statistical framework to estimate genotypes jointly from sequence reads, array intensities, and imputation. In European samples, we find similar sensitivity (89%) and specificity (99.6%) from imputation with either 1× sequencing or 1 M SNP arrays. Sensitivity is increased, particularly for low-frequency polymorphisms ([Image: see text]), when low coverage sequence reads are added to dense genome-wide SNP arrays — the converse, however, is not true. At sites where sequence reads and array intensities produce different sample genotypes, joint analysis reduces genotype errors and identifies novel error modes. Our joint framework informs the use of next-generation sequencing in genome wide association studies and supports development of improved methods for genotype calling. Public Library of Science 2012-07-12 /pmc/articles/PMC3395607/ /pubmed/22807667 http://dx.doi.org/10.1371/journal.pcbi.1002604 Text en Flannick et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Flannick, Jason Korn, Joshua M. Fontanillas, Pierre Grant, George B. Banks, Eric Depristo, Mark A. Altshuler, David Efficiency and Power as a Function of Sequence Coverage, SNP Array Density, and Imputation |
title | Efficiency and Power as a Function of Sequence Coverage, SNP Array Density, and Imputation |
title_full | Efficiency and Power as a Function of Sequence Coverage, SNP Array Density, and Imputation |
title_fullStr | Efficiency and Power as a Function of Sequence Coverage, SNP Array Density, and Imputation |
title_full_unstemmed | Efficiency and Power as a Function of Sequence Coverage, SNP Array Density, and Imputation |
title_short | Efficiency and Power as a Function of Sequence Coverage, SNP Array Density, and Imputation |
title_sort | efficiency and power as a function of sequence coverage, snp array density, and imputation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395607/ https://www.ncbi.nlm.nih.gov/pubmed/22807667 http://dx.doi.org/10.1371/journal.pcbi.1002604 |
work_keys_str_mv | AT flannickjason efficiencyandpowerasafunctionofsequencecoveragesnparraydensityandimputation AT kornjoshuam efficiencyandpowerasafunctionofsequencecoveragesnparraydensityandimputation AT fontanillaspierre efficiencyandpowerasafunctionofsequencecoveragesnparraydensityandimputation AT grantgeorgeb efficiencyandpowerasafunctionofsequencecoveragesnparraydensityandimputation AT bankseric efficiencyandpowerasafunctionofsequencecoveragesnparraydensityandimputation AT depristomarka efficiencyandpowerasafunctionofsequencecoveragesnparraydensityandimputation AT altshulerdavid efficiencyandpowerasafunctionofsequencecoveragesnparraydensityandimputation |