Our documentation pages have moved. Please go to https://research-help.genomicsengland.co.uk/ to navigate to the most up-to-date version of this page.

User experience and feedback is critical to maintaining and improving IVA.

Please send any feedback you have to [email protected] with 'IVA feedback' as the subject.

Overview

Interactive Variant Analysis (IVA) allows you to query variants and clinical data from participants from the 100,000 Genomes Project using an intuitive web interface. To open IVA, double-click on the desktop application. Then click Login on the top-right of the screen and enter your Research Environment credentials.

Only genomes which have been successfully processed through the Genomics England Interpretation pipeline are included in IVA. We can therefore be confident of the quality and integrity of the clinical and genomic data provided as genomes which fail quality control checks (such as contamination, genetic vs reported checks, coverage etc) are not included. Only small variants are included in IVA - structural variants can be accessed via the raw VCFs.

Available Data

As a GeCIP or Discovery Forum member, you will be able to query data from four different studies. You will be able to see a breakdown of these studies by clicking on the username tab on the top menu and selecting Projects.

Project	Study	Description	Genome Assembly	Number of samples	Number of variants	Aligner	Variant caller
100k Genomes Project GRCh37 Germline	RD37	Rare disease germline	GRCh37	12,166	289,435,693	Illumina iSAAC	Platypus (0.8.1)
100k Genomes Project GRCh38 Germline	RD38	Rare disease germline	GRCh38	33,190	439,334,686	Illumina iSAAC	Platypus (0.8.1)
100k Genomes Project GRCh38 Germline	CG38	Cancer germline	GRCh38	9,167	286,136,051	Illumina iSAAC	Starling (2.4.7)
100k Genomes Project GRCh38 Somatic	CS38	Cancer somatic	GRCh38	9,589	398,397,146	Illumina iSAAC	Strelka (2.4.7)

After logging in, click the Studies tab on the top menu to select your study. Be careful to note which study you are currently investigating!

Variant Browser

Once you have selected a study, click Variant Browser on the top menu. This browser allows you to view and filter variants for your chosen study using multiple parameters, which can be found in the left-hand menu. The filters available are:

Applying filters

Genomics England Research Environment > Interactive Variant Analysis (IVA) > image2019-3-14_11-31-21.png

Studies
- For studies on the within the same project (RD38 & CG8) you can apply AND/OR logic to filter for variants present in both studies or either one of the studies. Select the logic and tick the appropriate box fir your study of choice
Genomic
- Chromosomal location (by genomic coordinate)
- Feature IDs (genes, SNPs, transcripts)
- Gene disease panels (genes included in the chosen PanelApp panels)
- Biotype (gene or transcript type)
- Variant type - SNV (single nucleotide variant), MNV (multiple nucleotide variant), CNV (copy number variant), SV (structural variant) or INDEL (insertion/deletion)
Population frequency
- Population frequency as calculated overall or by population group in the 1000 Genomes and gnomAD databases
Consequence type
- Consequence type SO (Sequence ontology) terms. You can filter for all Loss-of-Function terms here
Deleteriousness
- Deleteriousness of variant using prediction tools SIFT, Polyphen and CADD (NB that CADD is only available in GRCh37 studies)
Conservation
- Conservation score as calculated by PhyloP, PhastCons and Gerp.

Gene ontology
- Gene ontology terms describing gene function
Phenotype-disease
- HPO (human phenotype ontology) accession IDs
- ClinVar accession IDs
- Full-text search on HPO, ClinVar, protein domains or keywords, and some OMIM and Orphanet IDs

Once you have defined your filters, click Search to show the resulting variants in table format, as in the screenshot below. (Summary format is not yet available.)

Genomics England Research Environment > Interactive Variant Analysis (IVA) > image2018-9-26_12-1-9.png

Remember to click Clear if you want to clear your applied filters. If you are experiencing issues with filtering, click Clear and re-try.

You can use this table to browse features of these variants, such as variant type, consequence type and population frequency. You can also download the table as a tab-separated values or JSON file.

Click on the row for a particular variant to view additional information on this variant below the table:

Samples gives a list of sample plating IDs that are heterozygous and homozygous mutant for the variant.
Cohort Stats does not take into account wild-type homozygotes due to the way the data are aggregated, and thus and thus genotype frequencies should be taken with a pinch of salt.
Advanced Annotation information and Beacon Network are not yet available.