Comparison of variant callers using 60 532 multi-ancestry whole genome sequences

Area of Science:

• Genomics
• Bioinformatics
• Human Genetics

Background:

• Whole genome sequencing (WGS) is crucial for understanding genetic factors in diseases and traits.
• Accurate variant calling is essential for downstream analyses like association studies and polygenic risk prediction.

Purpose of the Study:

• To compare the data quality, performance, and concordance of two widely used WGS variant callers: Genome Analysis Toolkit (GATK) and Variant Tool set (VT).

Main Methods:

• Analysis of 60,532 multi-ancestry whole genomes from the NHGRI Genome Sequencing Program's Centers for Common Disease Genomics (CCDG).
• Evaluation of GATK and VT pipelines for variant calling accuracy and consistency.

Main Results:

• Both GATK and VT pipelines produce highly consistent and reliable single nucleotide variants (SNVs) in large-scale WGS studies.
• Greater discrepancies were observed between GATK and VT in the calling of insertions and deletions (INDELs).

Conclusions:

• QCed GATK and VT pipelines demonstrate strong agreement for SNV calling in large WGS datasets.
• The choice of variant caller may impact results for INDEL detection in WGS studies.