Benchmarking Twist Genotyping-by-Sequencing Against Whole-Genome Sequencing in Nuclear Families
TL;DR
GxS performs slightly better than GSA by key concordance metrics, while slightly faltering behind GSA in inheritance analyses, indicating that GxS performs slightly better than GSA by key concordance metrics.
Abstract
Genome-wide genotyping is widely used in human genetics research, and targeted sequencing-based approaches such as the Twist Bioscience genome-wide SNP capture platform (GxS) have emerged as alternatives to conventional SNP arrays. Here, we evaluated GxS genotype calls from 555 individuals in 184 nuclear families against matched whole-genome sequencing (WGS) calls and compared platform performance with that of the Illumina Infinium Global Screening Array-24 (GSA), which was evaluated in 987 individuals from 279 nuclear families. Genotype data were harmonized across platforms, and analyses were restricted to overlapping SNP loci. Across all callable positions, mean per-SNP call rates were 98.31% for GxS and 98.77% for GSA. Overall SNP concordance with WGS was 99.78% for GxS and 99.66% for GSA. Mean per-individual concordance rates for GxS and GSA were matching their counterpart overall concordance rates when rounded to the nearest hundredth. Per-trio Mendelian violation rates of GxS are about 32 times those of WGS, while those of GSA are about 3.6 times those of WGS on average. These results indicate that GxS performs slightly better than GSA by key concordance metrics, while slightly faltering behind GSA in inheritance analyses.