Currently when calling variants you have to call variants on all people simultaneously, which allows for rare variant positions being check and called in every person without such variant.
My question is, why wouldn't it make more sense to just determine variant in every genomic position (3.2Billion) and that's it? You could merge this dataset with others easily, moreover, no need to do joint variant calling etc. It is very frustrating to see such an inefficiency becoming default.
•
written
by
optimistsso4co3 •
1 answer
You are correct, but you have conflated two issues - variant calling and warehousing. First, I don't think you will see joint genotyping being routinely done in 5 years - single sample calling with instrument-specific training sets are where things are headed. Secondly, the bigger groups are moving or have already moved to variant warehousing rather than VCFs - TileDB, Google Variant Transforms, GenomicsDB - and these want gVCFs as input.
Log in to answer this question.
-
What is more important for Structural Variant Calling? Recall or Precision?
written by Luke •
-
Analyse batch effect in WGS vcf files
written by Jasmin •
-
How to handle VCFs from the same sample but using different aligners and variant callers?
written by aldhairmedico •
-
Wha does combineGVCFs does to loci with variant only in gVCF from another analysis?
written by optimistsso4co3 •
-
Best way to find intervals for parallelization of joint variant calling
written by William
-
Tool: MAGERI: a software tool for calling rare variants and detecting circulating tumor DNA from UM…
written by mikhail.shugay
-
How should I calculate the variant density, per kb for a gene, for two different groups in a case/c…
written by anp375
-
Pipeline of structural variation calling using multiple tools for multiple samples
written by michealsmith
-
Tool: Variant Annotation, Analysis and Search Tool - VAAST2
written by Zev.Kronenberg
-
Tool: Vaast: Variant Annotation, Analysis And Search Tool
written by zx8754
storage is expensive.
This is false in two ways:
This is maddness. Current approach is extremely data intensive and additionally requires re-do of whole calling every time new sample comes around.
I've got more than 1000 WGS bams here. I'm frequently asked to re-genotypes a subset of samples using the latest version of gatk or with a new genotyper. Storing each vcf, in a join-genotyping world, is a nonsense.
Is there a paper that addresses why this is a nonsense? Vcf takes way less memory compared to BAM, and supposedly contains all the information to do that joint calling kinda allows. Like, GVCF is exactly that same VCF.
Doing this would mean you would have to sequence everything to higher coverage in order to confirm the rare variants are true and not artefacts. Joint-calling means you can get away with lower coverage.
Can you iterate further on this? Only benefit is determining better probabilities. However, you can save probability information in vcf and later merge with that in mind
If other individuals in the cohort also have the same variant, it makes it less likely to be a sequencing artefact than if you are looking at a single individual.
But you can't get the same information from already called VCFs, am i wrong?
unless the variant is associated with lower mapping or read quality, then the fact you see it recur in the same sequencing run makes it more likely it's an artefact