A reference data set of 5.4 million phased human variants validated by genetic inheritance from sequencing a three-generation 17-member pedigree
A reference data set of 5.4 million phased human variants validated by genetic inheritance from sequencing a three-generation 17-member pedigree
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DOI：
10.1101/gr.210500.116
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发表时间：
2017-01-01
期刊：
影响因子：
7
通讯作者：
Bentley, David R.
中科院分区：
文献类型：
--
作者：
Eberle, Michael A.;Fritzilas, Epameinondas;Bentley, David R.
要改进下一代序列数据中的变体调用，需要在一组基因组中调用一个全面的、全基因组范围的高置信度变体目录，作为基准使用。我们生成了三代谱系中17个个体的深层全基因组序列数据，并使用一系列当前可用的算法称为每个基因组中的变种。我们使用单倍型传递信息创建了一个阶段性的“白金”变异目录，包括470万个单核苷酸变异(SNV)和70万个小的(1-50bp)插入和缺失(INDel)，这些插入和缺失符合该家系父母和11个子女的遗传模式。白金基因与美国国家标准与技术研究所目前的SNV(99.99%)和INDELS(99.92%)目录高度一致，并增加了一个经过验证的TRUE目录，SNV增加了26%，INDELS增加了45%。对334,652个在信息学管道之间一致但与单倍型传递不一致的SNV进行的分析表明，这些变体中的大多数是从头开始的和细胞系突变，或者存在于以前未发现的复制和缺失中。这项研究的参考材料是客观评估整个基因组中变异呼叫的准确性的资源。
Improvement of variant calling in next-generation sequence data requires a comprehensive, genome-wide catalog of high confidence variants called in a set of genomes for use as a benchmark. We generated deep, whole-genome sequence data of 17 individuals in a three-generation pedigree and called variants in each genome using a range of currently available algorithms. We used haplotype transmission information to create a phased "Platinum" variant catalog of 4.7 million single nucleotide variants (SNVs) plus 0.7 million small (1-50 bp) insertions and deletions (indels) that are consistent with the pattern of inheritance in the parents and 11 children of this pedigree. Platinum genotypes are highly concordant with the current catalog of the National Institute of Standards and Technology for both SNVs (>99.99%) and indels (99.92%) and add a validated truth catalog that has 26% more SNVs and 45% more indels. Analysis of 334,652 SNVs that were consistent between informatics pipelines yet inconsistent with haplotype transmission ("nonpiatinum") revealed that the majority of these variants are de novo and cell-line mutations or reside within previously unidentified duplications and deletions. The reference materials from this study are a resource for objective assessment of the accuracy of variant calls throughout genomes.