Structural variant (SV) annotation.
git clone --recursive https://github.com/dellytools/sansa.git
cd sansa/
make all
Download an annotation database. Examples are gnomAD-SV or 1000 Genomes phase 3 and then run the annotation.
sansa annotate -d gnomad_v2.1_sv.sites.vcf.gz input.vcf.gz
The method generates two output files: anno.bcf with annotation SVs augmented by a unique ID (INFO/ANNOID) and query.tsv.gz with query SVs matched to annotation IDs.
bcftools can be used to extract all INFO fields you want as annotation. For instance, let's annotate with the VCF ID and EUR_AF for the European allele frequency in gnomad-SV. Always include INFO/ANNOID as the first column.
bcftools query -H -f "%INFO/ANNOID\t%ID\t%INFO/EUR_AF\n" anno.bcf | sed -e 's/^# //' > anno.tsv
Last is a simple join of query SVs with matched database SVs based on the first column (ANNOID).
join anno.tsv <(zcat query.tsv.gz | sort -k 1b,1) > results.tsv
Sansa matches SVs based on the absolute difference in breakpoint locations (-b) and the size ratio (-r) of the smaller SV compared to the larger SV. By default, the SVs need to have their start and end breakpoint within 50bp and differ in size by less than 20% (-r 0.8).
sansa annotate -b 50 -r 0.8 -d gnomad_v2.1_sv.sites.vcf.gz input.vcf.gz
By default, sansa only reports the best matching SVs. You can change the matching strategy to all using -s.
sansa annotate -s all -d gnomad_v2.1_sv.sites.vcf.gz input.vcf.gz
You can also include unmatched query SVs in the output using -m.
sansa annotate -m -d gnomad_v2.1_sv.sites.vcf.gz input.vcf.gz
By default, SVs are only compared within the same SV type (DELs with DELs, INVs with INVs, and so on). For delly this comparison is INFO/CT aware. You can deactivate this SV type check using -n.
sansa annotate -n -d gnomad_v2.1_sv.sites.vcf.gz input.vcf.gz
Based on a distance cutoff (-t) sansa matches SVs to nearby genes. The gene annotation file can be in gtf/gff2 or gff3 format.
sansa annotate -g Homo_sapiens.GRCh37.87.gtf.gz input.vcf.gz
sansa annotate -i Name -g Homo_sapiens.GRCh37.87.gff3.gz input.vcf.gz
The output has 2 columns for genes near the SV start breakpoint and genes near the SV end breakpoint. For each gene, the output lists the gene name and in paranthesis the distance (negative values: before SV breakpoint, 0: SV breakpoint within gene, positive values: after SV breakpoint) and the strand of the gene (+/-/*).
You can also use the Ensembl gene id or annotate exons instead of genes.
sansa annotate -i gene_id -g Homo_sapiens.GRCh37.87.gff3.gz input.vcf.gz
sansa annotate -f exon -i exon_id -g Homo_sapiens.GRCh37.87.gff3.gz input.vcf.gz
Gene and SV annotation can be run in a single command.
sansa annotate -g Homo_sapiens.GRCh37.87.gtf.gz -d gnomad_v2.1_sv.sites.vcf.gz input.vcf.gz
Using delly and the INFO/CT values one can identify gene fusion candidates. Here is the mapping from gene strand to CT values with classical cancer genomics examples (GRCh37 coordinates).
| chr | start | chr2 | end | svtype | ct | startfeature | endfeature |
|---|---|---|---|---|---|---|---|
| chrA | posStart | chrA | posEnd | INV | 3to3 | geneA(0;+) | geneB(0;-) |
| chrA | posStart | chrA | posEnd | INV | 3to3 | geneC(0;-) | geneD(0;+) |
| 10 | 89672219 | 10 | 90267336 | INV | 3to3 | PTEN(0;+) | RNLS(0;-) |
| chrA | posStart | chrA | posEnd | DEL | 3to5 | geneA(0;+) | geneB(0;+) |
| chrA | posStart | chrA | posEnd | DEL | 3to5 | geneC(0;-) | geneD(0;-) |
| 21 | 39887792 | 21 | 42869743 | DEL | 3to5 | ERG(0;-) | TMPRSS2(0;-) |
| chrA | posStart | chrA | posEnd | DUP | 5to3 | geneA(0;+) | geneB(0;+) |
| chrA | posStart | chrA | posEnd | DUP | 5to3 | geneC(0;-) | geneD(0;-) |
| 7 | 138547350 | 7 | 140491430 | DUP | 5to3 | KIAA1549(0;-) | BRAF(0;-) |
| chrA | posStart | chrA | posEnd | INV | 5to5 | geneA(0;+) | geneB(0;-) |
| chrA | posStart | chrA | posEnd | INV | 5to5 | geneC(0;-) | geneD(0;+) |
| 8 | 32139712 | 8 | 33359541 | INV | 5to5 | NRG1(0;+) | TTI2(0;-) |
| chrA | posA | chrB | posB | BND | 3to3 | geneA(0;+) | geneB(0;-) |
| chrA | posA | chrB | posB | BND | 3to3 | geneC(0;-) | geneD(0;+) |
| 14 | 68316364 | 5 | 58914908 | BND | 3to3 | RAD51B(0;+) | PDE4D(0;-) |
| chrA | posA | chrB | posB | BND | 3to5 | geneA(0;+) | geneB(0;+) |
| chrA | posA | chrB | posB | BND | 3to5 | geneC(0;-) | geneD(0;-) |
| 21 | 42867595 | 7 | 14027003 | BND | 3to5 | TMPRSS2(0;-) | ETV1(0;-) |
| chrA | posA | chrB | posB | BND | 5to3 | geneA(0;+) | geneB(0;+) |
| chrA | posA | chrB | posB | BND | 5to3 | geneC(0;-) | geneD(0;-) |
| 21 | 39826990 | 1 | 205637229 | BND | 5to3 | ERG(0;-) | SLC45A3(0;-) |
| chrA | posA | chrB | posB | BND | 5to5 | geneA(0;+) | geneB(0;-) |
| chrA | posA | chrB | posB | BND | 5to5 | geneC(0;-) | geneD(0;+) |
| 3 | 169190498 | 2 | 47689038 | BND | 5to5 | MECOM(0;-) | MSH2(0;+) |
Tobias Rausch, Thomas Zichner, Andreas Schlattl, Adrian M. Stuetz, Vladimir Benes, Jan O. Korbel.
DELLY: structural variant discovery by integrated paired-end and split-read analysis.
Bioinformatics. 2012 Sep 15;28(18):i333-i339.
https://doi.org/10.1093/bioinformatics/bts378
Sansa is distributed under the BSD 3-Clause license. Consult the accompanying LICENSE file for more details.