半面阳光 (2026-01-31 22:47):
#paper doi: https://doi.org/10.1038/s41467-025-67218-1. Nature Communications. 2025. Flexible read-aware genotype imputation from sequence using biobank sized reference panels. 这篇文章在先前的QUILT的基因型填充(Genotype Imputation)方法基础上开发了一个新的QUILT2方法。这个方法能够基于大规模单倍型参考panel数据,对低深度全基因组测序reads及游离DNA进行快速的单体型推断与基因型填充。此外,QUILT2还包含一个方法学上的创新,旨在通过NIPT数据实现对母体的和胎儿的基因组填充。
Flexible read-aware genotype imputation from sequence using biobank sized reference panels
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Abstract:
Abstract Inexpensive and accurate genotyping methods are essential to modern genomics and health risk prediction. Here we introduce QUILT2, a scalable and read-aware imputation method that can efficiently use biobank scale haplotype reference panels. This allows for fast and accurate imputation using short reads, as well as long reads (e.g. Oxford Nanopore Technologies (ONT) 1X, r2 = 0.937 at common SNPs), linked-reads and ancient DNA. In addition, QUILT2 contains a methodological innovation that is designed to enable imputation of the maternal and fetal genome using cell free non-invasive prenatal testing (NIPT) data. Using a UK Biobank reference panel and simulated NIPT data, we see accurate imputation of the mother (0.25X, r2 = 0.966, common SNPs) and modest imputation of the fetus (0.25X, r2 = 0.465, fetal fraction of 10%) at low coverage, with fetal imputation accuracy rising with coverage (4.0X, fetal r2 = 0.894). We show using simulated data that this could enable both GWAS and PRS for the mother and fetus, which could create clinical opportunities, and if phenotypes can be collected alongside clinical NIPT, the potential for large GWAS.
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