External links on this page can only be accessed from outside the RE 

Brief Overview

As part of the Main Programme V10 data release, we make available an aggregate multi-sample VCF (aggV2) comprising 78,195 germline genomes from the 100,000 Genomes Project on GRCh38. We also provide functional annotation files for all variants, variant and sample quality control (QC) metrics, inferred sample relatedness information, Principal Components, and inferred ancestry information for all samples in aggV2. 

Description

We have aggregated 78,195 germline gVCFs (genomic VCFs) from the 100,000 Genomes Project which we made available as a multi-sample VCF dataset (aggV2). aggV2 comprises over 722 million annotated single nucleotide variants and small indels (<=50bp) from quality controlled rare disease and cancer germline whole genomes. Note that there are significant changes from the aggV1 pipeline based upon the Main Programme V5.1 Data Release (59,464 samples). 

All samples in the dataset were sequenced with 150bp paired-end reads in a single lane of an Illumina HiSeq X instrument and uniformly processed on the Illumina North Star Version 4 Whole Genome Sequencing Workflow (NSV4, version 2.6.53.23); which comprises the iSAAC Aligner (version 03.16.02.19) and Starling Small Variant Caller (version 2.4.7). Samples were aligned to the Homo Sapiens NCBI GRCh38 assembly with decoys. 

The dataset was constructed from the aggregation of single-sample gVCFs using the Illumina software gVCF genotyper (version: 2019.02.26). Variant normalisation and decomposition was implemented by vt (version 0.57721). Genomic annotation and calculation of allele statistics (count, frequency etc.) was performed using Ensembl VEP and bcftools respectively. 

The multi-sample VCF is split into 1,371 roughly equal 'chunks' across the genome for faster processing. Each chunk contains the full set of samples and is in the VCF.gz file format with accompanying tabix index files (.tbi). Chromosomes 1-22, X, Y, and M are included. 

Extended Details

Each step of the pipeline to generate aggV2 is documented in the sections below: 

• Sample QC
• gVCF Aggregation
• Variant Normalisation
• Variant Representation
• Site QC, FILTER and INFO Fields
• Functional Annotation

FAQ & Code Book

A FAQ regarding all aggV2 queries can be found here: aggV2 FAQ

A code book of popular queries to help you use aggV2 is found here:  aggV2 Code Book

aggV2 Manifest & Location

Manifest

The aggV2 dataset comprises four main parts: 

1. A multi-sample VCF file for each chunk containing the genotypes and per variant quality metrics and filter flags
2. A corresponding VCF file for each chunk containing the functional (genomic) annotation and allele statistics for all variants
3. The aggregate_gvcf_sample_stats table in the Main Programme V10 LabKey folder which contains all sample quality metrics and accompanying meta-data
4. Associated files, based on aggV2, which may be useful for downstream analyses, such as Principal Components across all included samples, information on sample relatedness, and assignment of predicted super-population to each sample. Some of this information is also provided in LabKey, in the aggregate_gvcf_sample_stats table mentioned above.

Location

All aggV2 outputs can be found in the following folder within the Genomics England Research Environment: 

/gel_data_resources/main_programme/aggregation/aggregate_gVCF_strelka/aggV2/

This folder is accessible from the Desktop Environment and from the HPC as shown below:

Overview of Quality Control Flags

Variants in the multi-sample VCF files and annotation files are flagged against this set of basic site quality metrics. Note that hard variant filtering has not been applied to the dataset (no variants have been removed). 

Sample QC

All 78,195 samples included in aggV2 pass the following quality control filters:

Site Flags (FILTER)

The flags are presented within the FILTER column of the multi-sample VCF files and the annotation files as follows:

Site Metrics (INFO)

Per variant quality metrics were calculated and populated in the INFO field of the multi-sample VCF files and the annotation files. The INFO tags with descriptions are as follows: 

Help & Support