Rare variant phasing and haplotypic expression from RNA sequencing with phASER
Rare variant phasing and haplotypic expression from RNA sequencing with phASER
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DOI：
10.1038/ncomms12817
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发表时间：
2016-09-01
影响因子：
16.6
通讯作者：
Lappalainen, Tuuli
中科院分区：
文献类型：
--
作者：
Castel, Stephane E.;Mohammadi, Pejman;Lappalainen, Tuuli
遗传变体的单倍型定相对于基因组的临床解释、群体遗传分析和等位基因活性的功能基因组分析是重要的。在这里，我们提出了phASER，这是一种精确的方法，用于对测序读数重叠的变体进行定相，包括来自RNA测序（RNA-seq）的变体，由于剪接，这些变体通常跨越多个外显子。使用不同的RNA-seq数据，我们证明，与基于群体的定相相比，这提供了更准确的罕见变体定相，并允许在同一基因中的变体定相高达数百个不能从DNA测序（DNA-seq）读取获得的碱基序列。我们表明，在医学遗传学研究的背景下，这提高了复合杂合子的分辨率。此外，phASER提供了单倍型表达的测量，增加了等位基因表达研究的能力和准确性。总之，使用RNA-seq和phASER进行定相是准确的，并且改善了需要罕见变异单倍型或等位基因表达的研究。
Haplotype phasing of genetic variants is important for clinical interpretation of the genome, population genetic analysis and functional genomic analysis of allelic activity. Here we present phASER, an accurate approach for phasing variants that are overlapped by sequencing reads, including those from RNA sequencing (RNA-seq), which often span multiple exons due to splicing. Using diverse RNA-seq data we demonstrate that this provides more accurate phasing of rare variants compared with population-based phasing and allows phasing of variants in the same gene up to hundreds of kilobases away that cannot be obtained from DNA sequencing (DNA-seq) reads. We show that in the context of medical genetic studies this improves the resolution of compound heterozygotes. Additionally, phASER provides measures of haplotypic expression that increase power and accuracy in studies of allelic expression. In summary, phasing using RNA-seq and phASER is accurate and improves studies where rare variant haplotypes or allelic expression is needed.