Abstract：
Rapid advances in high-throughput DNA sequencing technologies have enabled the conduct of whole genome sequencing (WGS) studies, and several bioinformatics pipelines have become available. The aim of this study was the comparison of 6 WGS data pre-processing pipelines, involving two mapping and alignment approaches (GATK utilizing BWA-MEM2 2.2.1, and DRAGEN 3.8.4) and three variant calling pipelines (GATK 4.2.4.1, DRAGEN 3.8.4 and DeepVariant 1.1.0). We sequenced one genome in a bottle (GIAB) sample 70 times in different runs, and one GIAB trio in triplicate. The truth set of the GIABs was used for comparison, and performance was assessed by computation time, F1 score, precision, and recall. In the mapping and alignment step, the DRAGEN pipeline was faster than the GATK with BWA-MEM2 pipeline. DRAGEN showed systematically higher F1 score, precision, and recall values than GATK for single nucleotide variations (SNVs) and Indels in simple-to-map, complex-to-map, coding and non-coding regions. In the variant calling step, DRAGEN was fastest. In terms of accuracy, DRAGEN and DeepVariant performed similarly and both superior to GATK, with slight advantages for DRAGEN for Indels and for DeepVariant for SNVs. The DRAGEN pipeline showed the lowest Mendelian inheritance error fraction for the GIAB trios. Mapping and alignment played a key role in variant calling of WGS, with the DRAGEN outperforming GATK.
摘要：
高通量DNA测序技术的快速发展使得全基因组测序(WGS)研究得以开展。和几个生物信息学管道已经成为可用。本研究的目的是比较6个WGS数据预处理管道，涉及两种映射和对齐方法(利用BWA-MEM22.2.1和DRAGEN3.8.4的GATK)和三种变体调用管道(GATK4.2.4.1、DRAGEN3.8.4和DeepVariant1.1.0)。我们在不同的运行中对瓶（GIAB）样品中的一个基因组进行了70次测序，和一个GIAB三重奏一式三份。GIAB的真值集用于比较，性能是通过计算时间来评估的，F1得分,精度,和回忆。在映射和对齐步骤中，DRAGEN管道比使用BWA-MEM2管道的GATK快。DRAGEN表现出系统性较高的F1得分，精度,对于简单映射中的单核苷酸变异（SNV）和Indels，复杂的地图，编码区和非编码区。在变体调用步骤中，DRAGEN是最快的。在准确性方面,DRAGEN和DeepVariant的表现相似，都优于GATK，对于Indels的DRAGEN和SNV的DeepVariant具有轻微的优势。DRAGEN管道显示GIAB三重奏的最低孟德尔继承错误分数。映射和对齐在WGS的变体调用中起着关键作用，DRAGEN胜过GATK。
