Calling germline SNPs using GATK HaplotypeCaller in a single sample
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4.1 years ago
vctrm67 ▴ 50

I am using GATK 4.1.2.0. What is the best way to call germline variants from single samples? I have a cohort of samples and want very high sensitivity to capture individual-specific germline mutations, which I think would be impossible with GenotypeGVCFs, since that seems to utilize cohort mutation frequency to boost confidence.

I see that HaplotypeCaller is able to run without the -ERC GVCF flag; I also see from here (https://gatk.broadinstitute.org/hc/en-us/articles/360036897532-HaplotypeCaller ) that I could then run variant recalibration afterwards (I assume with GATK VQSR). Is this all I need to do?

If so, should I follow the default parameters and databases set forth in the Github (https://github.com/gatk-workflows/gatk4-germline-snps-indels/blob/3087accf86b325bb5b511f2e7f6e8574fc0c1ff0/joint-discovery-gatk4.wdl)? I'm not quite sure how best to utilize the databases and set the parameters for "known, truth, prior,.." etc. Would appreciate advice from anyone who has experience.

Also I posted this in the GATK forum but they take way too long to respond.

GATK • 1.2k views
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