Identification of somatic mutations in single cell DNA-seq using a spatial model of allelic imbalance.,Nature Communications

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Identification of somatic mutations in single cell DNA-seq using a spatial model of allelic imbalance.
Nature Communications ( IF 14.7 ) Pub Date : 2019-08-29 , DOI: 10.1038/s41467-019-11857-8
Lovelace J Luquette ₁ , Craig L Bohrson ₁ , Max A Sherman ₁ , Peter J Park _{1,

2}

Affiliation

Recent advances in single cell technology have enabled dissection of cellular heterogeneity in great detail. However, analysis of single cell DNA sequencing data remains challenging due to bias and artifacts that arise during DNA extraction and whole-genome amplification, including allelic imbalance and dropout. Here, we present a framework for statistical estimation of allele-specific amplification imbalance at any given position in single cell whole-genome sequencing data by utilizing the allele frequencies of heterozygous single nucleotide polymorphisms in the neighborhood. The resulting allelic imbalance profile is critical for determining whether the variant allele fraction of an observed mutation is consistent with the expected fraction for a true variant. This method, implemented in SCAN-SNV (Single Cell ANalysis of SNVs), substantially improves the identification of somatic variants in single cells. Our allele balance framework is broadly applicable to genotype analysis of any variant type in any data that might exhibit allelic imbalance.

中文翻译：

使用等位基因不平衡的空间模型鉴定单细胞DNA-seq中的体细胞突变。

单细胞技术的最新进展使得能够对细胞异质性进行详细的剖析。但是，由于DNA提取和全基因组扩增过程中出现的偏倚和伪影，包括等位基因失衡和缺失，对单细胞DNA测序数据的分析仍然具有挑战性。在这里，我们提出了一个框架，通过利用附近杂合单核苷酸多态性的等位基因频率，对单细胞全基因组测序数据中任意给定位置的等位基因特异性扩增不平衡进行统计估计。所得的等位基因失衡图谱对于确定观察到的突变的变异等位基因部分是否与真实变异的预期部分一致是至关重要的。此方法在SCAN-SNV（SNV的单细胞分析）中实现，大大改善了单细胞体细胞变异的鉴定。我们的等位基因平衡框架广泛适用于可能显示等位基因失衡的任何数据中任何变异类型的基因型分析。

更新日期：2019-08-29

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