Atlas Biomed Group Limited, Tintagel House, 92 Albert Embankment, Lambeth, London, SE1 7TY, UK.
Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, bld. 1, 121205, Moscow, Russia.
BMC Genomics. 2020 Sep 10;21(Suppl 7):528. doi: 10.1186/s12864-020-06919-x.
Head-to-head comparison of BeadChip and WGS/WES genotyping techniques for their precision is far from straightforward. A tool for validation of high-throughput genotyping calls such as Sanger sequencing is neither scalable nor practical for large-scale DNA processing. Here we report a cross-validation analysis of genotyping calls obtained via Illumina GSA BeadChip and WGS (Illumina HiSeq X Ten) techniques.
When compared to each other, the average precision and accuracy of BeadChip and WGS genotyping techniques exceeded 0.991 and 0.997, respectively. The average fraction of discordant variants for both platforms was found to be 0.639%. A sliding window approach was utilized to explore genomic regions not exceeding 500 bp encompassing a maximal amount of discordant variants for further validation by Sanger sequencing. Notably, 12 variants out of 26 located within eight identified regions were consistently discordant in related calls made by WGS and BeadChip. When Sanger sequenced, a total of 16 of these genotypes were successfully resolved, indicating that a precision of WGS and BeadChip genotyping for this genotype subset was at 0.81 and 0.5, respectively, with accuracy values of 0.87 and 0.61.
We conclude that WGS genotype calling exhibits higher overall precision within the selected variety of discordantly genotyped variants, though the amount of validated variants remained insufficient.
BeadChip 和 WGS/WES 两种基因分型技术在精确性方面的直接比较远非易事。对于高通量基因分型调用（如 Sanger 测序）的验证工具，既不可扩展也不适合大规模 DNA 处理。在这里，我们报告了通过 Illumina GSA BeadChip 和 WGS（Illumina HiSeq X Ten）技术获得的基因分型调用的交叉验证分析。
相互比较时，BeadChip 和 WGS 基因分型技术的平均精度和准确性分别超过 0.991 和 0.997。发现两个平台的不一致变异体比例的平均值为 0.639%。采用滑动窗口方法探索不超过 500 bp 的基因组区域，以通过 Sanger 测序进一步验证，这些区域包含最多数量的不一致变异体。值得注意的是，26 个位于 8 个已识别区域内的变异体中有 12 个在 WGS 和 BeadChip 的相关调用中始终不一致。当对这些进行 Sanger 测序时，总共成功解决了 16 种基因型，表明 WGS 和 BeadChip 对该基因型子集的基因分型精度分别为 0.81 和 0.5，准确率分别为 0.87 和 0.61。
我们得出结论，WGS 基因型调用在所选不一致基因型的变异体中表现出更高的总体精度，尽管验证的变异体数量仍然不足。
