Genome measures used for quality control are dependent on gene function and ancestry
Genome measures used for quality control are dependent on gene function and ancestry
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DOI：
10.1093/bioinformatics/btu668
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发表时间：
2015-02-01
期刊：
影响因子：
5.8
通讯作者：
Guo, Yan
中科院分区：
文献类型：
--
作者：
Wang, Jing;Raskin, Leon;Guo, Yan
动机：转换/颠换 (Ti/Tv) 比率和杂合/非参考纯合 (het/nonref-hom) 比率在遗传研究中通常被计算为质量控制 (QC) 测量。此外，这两个比率有助于我们理解 DNA 序列进化的模式。 结果：为了彻底了解这两个基因组测量值，我们使用 1000 个基因组计划 (1000G) 发布的基因型数据 (N = 1092) 进行了一项研究。另外两个数据集（N = 581 和 N = 6）用于验证我们在 1000G 数据集中的发现。我们比较了大陆血统、基因组区域和基因功能之间的两个比率。我们发现Ti/Tv比值可以作为从高通量测序数据推断单核苷酸多态性的质量指标。 Ti/Tv 比率因基因组区域和功能而异，但不因血统而异。 het/nonref-hom 比率因祖先而异，但不因基因组区域和功能而异。此外，鸟嘌呤 + 胞嘧啶的极端含量（无论高还是低）与 Ti/Tv 比值负相关。因此，当使用这两种方法进行质量控制评估时，必须注意根据血统和基因组区域应用正确的阈值。如果在质量控制阶段未能考虑到这些因素，任何后续分析都会产生偏差。
Motivation: The transition/transversion (Ti/Tv) ratio and heterozygous/nonreference-homozygous (het/nonref-hom) ratio have been commonly computed in genetic studies as a quality control (QC) measurement. Additionally, these two ratios are helpful in our understanding of the patterns of DNA sequence evolution.Results: To thoroughly understand these two genomic measures, we performed a study using 1000 Genomes Project (1000G) released genotype data (N = 1092). An additional two datasets (N = 581 and N = 6) were used to validate our findings from the 1000G dataset. We compared the two ratios among continental ancestry, genome regions and gene functionality. We found that the Ti/Tv ratio can be used as a quality indicator for single nucleotide polymorphisms inferred from high-throughput sequencing data. The Ti/Tv ratio varies greatly by genome region and functionality, but not by ancestry. The het/nonref-hom ratio varies greatly by ancestry, but not by genome regions and functionality. Furthermore, extreme guanine + cytosine content (either high or low) is negatively associated with the Ti/Tv ratio magnitude. Thus, when performing QC assessment using these two measures, care must be taken to apply the correct thresholds based on ancestry and genome region. Failure to take these considerations into account at the QC stage will bias any following analysis.