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科学家开发出基因分型的新方法
2021-06-06 15:37

英国牛津大学Robert W. Davies团队开发出基因分型的新方法。相关论文于2021年6月3日在线发表于国际学术期刊《自然—遗传学》。

研究人员报道了QUILT,它使用低覆盖率的全基因组序列数据执行二倍体基因型填充。QUILT采用吉布斯采样将读数划分为母本和父本集,并使用大型参考面板促进快速单倍体填充。研究人员证明了这种划分在许多兆碱基上是准确的,能够实现接近理论极限的高精度插补,并且优于现有方法。此外,QUILT可以使用多种技术进行准确估算,包括来自Oxford Nanopore Technologies的长读数,以及一种称为haplotagging的低成本条形码Illumina测序新形式,后者在低覆盖率下显示出更高的准确性。

相对于DNA基因分型微阵列,QUILT以更低的成本提供更高的准确性,特别是对于传统上在现代基因组分析中应用不足的不同人群,并且在稀有SNP上的准确性几乎翻了一番。最后,QUILT可以准确地推断(四位数)人类白细胞抗原类型,这是第一个从低覆盖率序列数据中提取的此类方法。

据了解,廉价的基因分型方法对现代基因组学至关重要。

附:英文原文

Title: Rapid genotype imputation from sequence with reference panels

Author: Robert W. Davies, Marek Kucka, Dingwen Su, Sinan Shi, Maeve Flanagan, Christopher M. Cunniff, Yingguang Frank Chan, Simon Myers

Issue&Volume: 2021-06-03

Abstract: Inexpensive genotyping methods are essential to modern genomics. Here we present QUILT, which performs diploid genotype imputation using low-coverage whole-genome sequence data. QUILT employs Gibbs sampling to partition reads into maternal and paternal sets, facilitating rapid haploid imputation using large reference panels. We show this partitioning to be accurate over many megabases, enabling highly accurate imputation close to theoretical limits and outperforming existing methods. Moreover, QUILT can impute accurately using diverse technologies, including long reads from Oxford Nanopore Technologies, and a new form of low-cost barcoded Illumina sequencing called haplotagging, with the latter showing improved accuracy at low coverages. Relative to DNA genotyping microarrays, QUILT offers improved accuracy at reduced cost, particularly for diverse populations that are traditionally underserved in modern genomic analyses, with accuracy nearly doubling at rare SNPs. Finally, QUILT can accurately impute (four-digit) human leukocyte antigen types, the first such method from low-coverage sequence data. QUILT is a method for rapid genotype imputation and phasing from low-coverage whole-genome sequence data using a large haplotype reference panel. QUILT enables highly accurate imputation across a range of coverages and data types.

DOI: 10.1038/s41588-021-00877-0

Source: https://www.nature.com/articles/s41588-021-00877-0

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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