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collapse
collapse is Truvari's approach to SV merging. After leveraging bcftools to merge VCFs, truvari collapse can then iterate over the calls and create clusters of SVs that match over the provided thresholds. This is also useful when removing potentially redundant calls within a single sample.
Since collapse uses the same variant comparison engine as bench, there is a lot of overlap in the behavior. Be sure to also be familiar with the bench documentation.
To start, we merge multiple VCFs (each with their own sample) and ensure there are no multi-allelic entries via:
bcftools merge -m none one.vcf.gz two.vcf.gz | bgzip > merge.vcf.gzWARNING! If you have symbolic variants, see the below section on using bcftools.
This will paste SAMPLE information between vcfs when calls have the exact same chrom, pos, ref, and alt.
For example, consider two vcfs:
>> one.vcf:
chr1 1 ... GT 0/1
chr1 5 ... GT 1/1
>> two.vcf:
chr1 1 ... GT 1/1
chr1 7 ... GT 0/1
bcftools merge creates:
>> merge.vcf:
chr1 1 ... GT 0/1 1/1
chr1 5 ... GT 1/1 ./.
chr1 7 ... GT ./. 0/1
This VCF can then be collapsed to allow 'fuzzier' matching than the exact merge just performed.
truvari collapse -i merge.vcf.gz -o truvari_merge.vcf -c truvari_collapsed.vcfFor example, if we collapsed our example merge.vcf by matching any calls within 3bp, we'd create:
>> truvari_merge.vcf
chr1 1 ... GT 0/1 1/1
chr1 5 ... GT 1/1 0/1
>> truvari_collapsed.vcf
chr1 7 ... GT ./. 0/1
bcftools may not handle symbolic variants correctly since it doesn't consider their END position. To correct for this, ensure that every input variant has a unique ID and use bcftools merge -m id. For example:
# A.vcf
chr1 147022730 SV1 N <DEL> . PASS SVLEN=-570334;END=147593064
# B.vcf
chr1 147022730 SV2 N <DEL> . PASS SVLEN=-990414;END=148013144
# bcftools merge -m none A.vcf B.vcf
# Premature collapse
chr1 147022730 SV1;SV2 N <DEL> . PASS SVLEN=-570334;END=147593064
# bcftools merge -m id A.vcf B.vcf
chr1 147022730 SV1 N <DEL> . PASS SVLEN=-570334;END=147593064
chr1 147022730 SV2 N <DEL> . PASS SVLEN=-990414;END=148013144
This bug has been replicated with bcftools 1.18 and 1.21.
When collapsing, the default --choose behavior is to take the first variant by position from a cluster to
be written to the output while the others will be placed in the collapsed output.
Other choosing options are maxqual (the call with the highest quality score) or common (the call with the highest minor allele count).
Samples with no genotype information in the kept variant will be filled by the first collapsed variant containing genotype information.
For some results, one may not want to collapse variants with conflicting genotypes from a single sample. With the --gt all parameter, variants which are present (non 0/0 or ./.) in the same sample are not collapsed. With the -gt het parameter, only variants which are both heterozygous in a sample (e.g. 0/1 and 0/1) are prevented from collapsing. The --gt het is useful for some SV callers which will redundantly call variants and typically genotype them all as 1/1.
When a single sample is run through multiple SV callers, one may wish to consolidate those results. After the bcftools merge of the VCFs, there will be one SAMPLE column per-input. With --intra, collapse will consolidate the sample information so that only a single sample column is present in the output. Since the multiple callers may have different genotypes or other FORMAT fields with conflicting information, --intra takes the first column from the VCF, then second, etc. For example, if we have an entry with:
FORMAT RESULT1 RESULT2
GT:GQ:AD ./.:.:3,0 1/1:20:0,30
The --intra output would be:
FORMAT RESULT1
GT:GQ:AD 1/1:20:3,0
As you can see in this example, 1) The first sample name is the only one preserved. 2) conflicting FORMAT fields can be consolidated in a non-useful way (here the AD of 3,0 isn't informative to a 1/1 genotype). We're working to provide an API to help users write custom intra-sample consolidation scripts.
When using --hap, we assume phased variants from a single individual. Only the
single best matching call from the other haplotype will be collapsed,
and the consolidated genotype will become 1/1
For example, if we collapse anything at the same position:
chr1 1 .. GT 0|1
chr1 1 .. GT 1|0
chr1 2 .. GT 1|0
will become:
chr1 1 .. GT 1/1
chr1 2 .. GT 1|0
Normally, every variant in a set of variants that are collapsed together matches every other variant in the set. However, when using --chain mode, we allow 'transitive matching'. This means that all variants match to only at least one other variant in the set. In situations where a 'middle' variant has two matches that don't match each other, without --chain the locus will produce two variants whereas using --chain will produce one.
For example, if we have
chr1 1 ..
chr1 4 ..
chr1 7 ..
chr1 10 ..
We take the chr1 1 variant and find all its matches. When we collapse anything within 5bp of each other, without --chain, we output:
chr1 1 ..
chr1 7 ..
With --chain, we would allow one level of transitive matching. This means that after finding the chr1 1 -> chr1 4 match, we check chr1 4 against all the remaining variants and would output
chr1 1 ..
chr1 10 ..
Note that this leaves chr1 10 because we don't do multiple levels of transitive matching, meaning we never compare chr1 7 to chr1 10. This is preferred because otherwise variants which have a continuous range of similarity could all be collapsed into a single variant. e.g., if the position in this example were sizes and, we wouldn't want the 1bp variant being a kept representation for all the variants.
collapse produces two files. The output file has kept variants along with unanalyzed (< sizemin) variants. The collapsed file contains the variants that were collapsed into the kept variants.
The output file has only two annotations added to the INFO.
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CollapseId- Identifier of the variant when comparing to the collapse outputs. -
NumCollapsed- Number of variants collapsed into this variant -
NumConsolidated- Number of samples' genotypes consolidated into this call's genotypes
The collapsed file has all of the annotations added by bench. Note that MatchId is tied to the output file's CollapseId. See MatchIds for details.