Systematic comparison of variant calling pipelines using gold standard personal exome variants.
Systematic comparison of variant calling pipelines using gold standard personal exome variants.
复制标题
DOI：
10.1038/srep17875
复制
发表时间：
2015-12-07
影响因子：
4.6
通讯作者：
Marcotte EM
中科院分区：
文献类型：
--
作者：
Hwang S;Kim E;Lee I;Marcotte EM
使用下一代测序（NGS）的临床基因组学的成功需要准确和一致地识别个人基因组变异。已经开发了各种变体调用方法，这些方法在它们的调用之间显示出低一致性。因此，系统地比较变异呼叫者可以为基于NGS的临床基因组学提供重要指导。最近，瓶内基因组（GIAB）联盟发布了一组针对一个个体（NA 12878）的高置信度变体调用，从而实现了不同变体调用管道的性能基准测试。基于来自GIAB的金标准参考变体调用，我们比较了13个变体调用管道的性能，测试了三个读取比对器-BWA-MEM、Bowtie 2和Novofiler-和四个变体调用器-基因组分析工具包HaplotypeCaller（GATK-HC）、Samtools mpileup、Freebayes和Ion Proton Variant Caller（TVC）的组合，通过包括Illumina 2000、Illumina 2500和Ion Proton的不同平台测序的NA 12878基因组的12个数据集，具有各种外显子组捕获系统和外显子组覆盖率。我们观察到不同的变异呼叫者对特定类型的SNP基因分型错误的不同偏倚。我们的研究结果为从个人基因组的深度测序中进行可靠的变体鉴定提供了有用的指导。
The success of clinical genomics using next generation sequencing (NGS) requires the accurate and consistent identification of personal genome variants. Assorted variant calling methods have been developed, which show low concordance between their calls. Hence, a systematic comparison of the variant callers could give important guidance to NGS-based clinical genomics. Recently, a set of high-confident variant calls for one individual (NA12878) has been published by the Genome in a Bottle (GIAB) consortium, enabling performance benchmarking of different variant calling pipelines. Based on the gold standard reference variant calls from GIAB, we compared the performance of thirteen variant calling pipelines, testing combinations of three read aligners—BWA-MEM, Bowtie2, and Novoalign—and four variant callers—Genome Analysis Tool Kit HaplotypeCaller (GATK-HC), Samtools mpileup, Freebayes and Ion Proton Variant Caller (TVC), for twelve data sets for the NA12878 genome sequenced by different platforms including Illumina2000, Illumina2500, and Ion Proton, with various exome capture systems and exome coverage. We observed different biases toward specific types of SNP genotyping errors by the different variant callers. The results of our study provide useful guidelines for reliable variant identification from deep sequencing of personal genomes.