Comparison of calling pipelines for whole genome sequencing: an empirical study demonstrating the importance of mapping and alignment
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Comparison of calling pipelines for whole genome sequencing: an empirical study demonstrating the importance of mapping and alignment. / Betschart, Raphael O; Thiéry, Alexandre; Aguilera-Garcia, Domingo; Zoche, Martin; Moch, Holger; Twerenbold, Raphael; Zeller, Tanja; Blankenberg, Stefan; Ziegler, Andreas.
In: SCI REP-UK, Vol. 12, No. 1, 21502, 13.12.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Comparison of calling pipelines for whole genome sequencing: an empirical study demonstrating the importance of mapping and alignment
AU - Betschart, Raphael O
AU - Thiéry, Alexandre
AU - Aguilera-Garcia, Domingo
AU - Zoche, Martin
AU - Moch, Holger
AU - Twerenbold, Raphael
AU - Zeller, Tanja
AU - Blankenberg, Stefan
AU - Ziegler, Andreas
N1 - © 2022. The Author(s).
PY - 2022/12/13
Y1 - 2022/12/13
N2 - 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.
AB - 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.
KW - Polymorphism, Single Nucleotide
KW - Whole Genome Sequencing
KW - High-Throughput Nucleotide Sequencing
KW - Computational Biology
KW - INDEL Mutation
KW - Software
U2 - 10.1038/s41598-022-26181-3
DO - 10.1038/s41598-022-26181-3
M3 - SCORING: Journal article
C2 - 36513709
VL - 12
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
IS - 1
M1 - 21502
ER -