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. 2019 Dec 30:4:50.
doi: 10.12688/wellcomeopenres.15126.2. eCollection 2019.

Variant calling on the GRCh38 assembly with the data from phase three of the 1000 Genomes Project

Ernesto Lowy-Gallego  1 , Susan Fairley  1 , Xiangqun Zheng-Bradley  1 , Magali Ruffier  1 , Laura Clarke  1 , Paul Flicek  1 ; 1000 Genomes Project Consortium
Affiliations

Variant calling on the GRCh38 assembly with the data from phase three of the 1000 Genomes Project

Ernesto Lowy-Gallego et al. Wellcome Open Res. .

Abstract

We present a set of biallelic SNVs and INDELs, from 2,548 samples spanning 26 populations from the 1000 Genomes Project, called de novo on GRCh38. We believe this will be a useful reference resource for those using GRCh38. It represents an improvement over the "lift-overs" of the 1000 Genomes Project data that have been available to date by encompassing all of the GRCh38 primary assembly autosomes and pseudo-autosomal regions, including novel, medically relevant loci. Here, we describe how the data set was created and benchmark our call set against that produced by the final phase of the 1000 Genomes Project on GRCh37 and the lift-over of that data to GRCh38.

Keywords: Genomics; population genetics; single nucleotide variation; variant calling; variant discovery.

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Conflict of interest statement

No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. Schematic representation of our approach illustrating the entire process from the alignment files previously generated to the generation of the four supporting callsets and finally to the production of the final phased consensus callset.
VCF, variant call format; WGS, whole-genome sequencing; WES, whole-exome sequencing; VQSR, variant quality score recalibration.
Figure 2.
Figure 2.. UpSet plot analysing the contribution of each of the four supporting call sets to the final SNV consensus call set.
‘ex_bcftools’ is the call set generated using BCFTools with the WES (Whole exome sequencing) data. ‘lc_bcftools’ is the call set generated using BCFTools with the low coverage WGS (whole genome sequencing) data. ‘freebayes’ is the call set generated using Freebayes with the low coverage WGS+WES data. ‘gatk’ is the call set generated using GATK UnifiedGenotyper with the low coverage WGS data. ‘consensus’ is the final SNV call set generated after integrating the supporting call sets. Vertical bars show the size of the intersection between the call sets. Horizontal bars show the aggregated size of each call set. We used the filtered supporting call sets to generate this plot.
Figure 3.
Figure 3.. UpSet plot analysing the contribution of each of the four supporting call sets to the final INDEL consensus call set.
‘ex_bcftools’ is the call set generated using BCFTools with the WES (Whole exome sequencing) data. ‘lc_bcftools’ is the call set generated using BCFTools with the low coverage WGS (whole genome sequencing) data. ‘freebayes’ is the call set generated using Freebayes with the low coverage WGS+WES data. ‘gatk’ is the call set generated using GATK UnifiedGenotyper with the low coverage WGS data. ‘consensus’ is the final INDEL call set generated after integrating the supporting call sets. Vertical bars show the size of the intersection between the call sets. Horizontal bars show the aggregated size of each call set. We used the filtered supporting call sets to generate this plot.
Figure 4.
Figure 4.. Variants in regions containing clinically relevant genes that had coding sequence splits over assembly gaps in GRCh37 that have been filled in GRCh38.
‘ 1KG native’: call set presented in this work; ‘ 1KG All SNPs/indels’: lift-over call set.
Figure 5.
Figure 5.. Percentage of SNVs that are true positives in the comparison with the NA12878 call set from GIAB for contigs added to GRCh38 across the different autosomes.
‘ TP_igsr’ is the percentage of true positives for our call set. ‘ TP_liftover’ is the percentage of true positives for the lift-over call set.
See this image and copyright information in PMC

References

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