Scientific Publications

Efficiency and power as a function of sequence coverage, SNP array density, and imputation.

Publication TypeJournal Article
AuthorsFlannick, J., Korn JM, Fontanillas P., Grant GB, Banks E., DePristo MA, and Altshuler D.
AbstractHigh 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 ([Formula: 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.
Year of Publication2012
JournalPLoS computational biology
Volume8
Issue7
Pagese1002604
Date Published (YYYY/MM/DD)2012/07/01
ISSN Number1553-734X
DOI10.1371/journal.pcbi.1002604
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/22807667?dopt=Abstract