Benchmarking Twist Genotyping-by-Sequencing Against Whole-Genome Sequencing in Nuclear Families
- 1Albert Einstein College of Medicine
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 98.26% for GxS and 98.67% for GSA. Overall SNP concordance with WGS was 99.79% for GxS and 99.87% for GSA, and mean per-individual concordance was also 99.79% and 99.87%, respectively. Per-trio Mendelian violation rates of GxS are about 10 times those of WGS, while those of GSA are about 4 times those of WGS on average. These results indicate that GxS performs slightly worse than GSA by key concordance and inheritance metrics, while still showing strong overall agreement with WGS.
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BibTeX
@misc{klugerman2026benchmarking,
title = {{Benchmarking Twist Genotyping-by-Sequencing Against Whole-Genome Sequencing in Nuclear Families}},
author = {J. Klugerman and I. Iossifov and K. Ye},
howpublished = {bioRxiv},
year = {2026},
month = jul,
doi = {10.64898/2026.07.31.742127},
url = {https://www.biorxiv.org/content/10.64898/2026.07.31.742127v3},
note = {CC BY},
}
RIS
TY - UNPB
TI - Benchmarking Twist Genotyping-by-Sequencing Against Whole-Genome Sequencing in Nuclear Families
AU - J. Klugerman
AU - I. Iossifov
AU - K. Ye
PY - 2026
DA - 2026/07/31
PB - bioRxiv
DO - 10.64898/2026.07.31.742127
UR - https://www.biorxiv.org/content/10.64898/2026.07.31.742127v3
AB - 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 98.26% for GxS and 98.67% for GSA. Overall SNP concordance with WGS was 99.79% for GxS and 99.87% for GSA, and mean per-individual concordance was also 99.79% and 99.87%, respectively. Per-trio Mendelian violation rates of GxS are about 10 times those of WGS, while those of GSA are about 4 times those of WGS on average. These results indicate that GxS performs slightly worse than GSA by key concordance and inheritance metrics, while still showing strong overall agreement with WGS.
ER -