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Test-drive the GATK tools and Best Practices pipelines on Terra
Check out this blog post to learn how you can get started with GATK and try out the pipelines in preconfigured workspaces (with a user-friendly interface!) without having to install anything.
ExcessHet filtering in cohorts with family members
This post mentions that the first step in Best Practice VQSR filtering involves hard filtering on ExcessHet. The post also states that "ExcessHet filtering applies only to callsets with a large number of samples, e.g. hundreds of unrelated samples."
I have a cohort of 170 samples from 70 families. Each family consists of either a trio, duo or singleton, depending on who I could recruit. Some of these families are consanguineous. Each family has a different undiagnosed rare disease and I am trying to find the causal variant in each family. The whole 170 samples were aligned and variant called following GATK Best Practices. No pedigree file was used during variant calling. In a sample VCF from this cohort, there are 4.9 Million variants, 124'00 of which are flagged as 'ExcessHet'. My question is: can I treat the variants flagged as 'ExcessHet' as likely false positives or does the fact that my cohort consists of multiple unrelated families make the 'ExcessHet' filter unreliable?
I don't really understand why ExcessHet filtering is needed in the VQSR workflow, so if you could explain what ExcessHet does in this context, this would be great!