Proposed Analysis: Filter germline variants for MB subtyping

[jharenza]

What are the scientific goals of the analysis?

Filter germline variants for deleterious variants within TP53, SUFU, and PTCH1 to enable #247

What methods do you plan to use to accomplish the scientific goals?

Using Annovar annotations,

• keep those with sequencing depth DP > 10
• keep those with alternative allele depth AD > 0.25 * sum of all AD's. E.g. assuming the vcf FORMAT field is GT:AD:DP, if the sample sequencing data is 0/1:19,9:28 then keep this variant; if 0/1:19,6:25 then discard this variant.
• keep those with AAChange.refGene not being .
• keep those with allele frequency < 0.01 in the gnomAD datasets. There are three frequencies gnomad211_exome_AF=, gnomad211_genome_AF= and gnomad30_genome_AF=, and make sure the smallest among them are less than 0.01.

What input data are required for this analysis?

germline VCFs, controlled access

How long do you expect is needed to complete the analysis? Will it be a multi-step analysis?

1 week

Who will complete the analysis (please add a GitHub handle here if relevant)?

@yiran-guo

What relevant scientific literature relates to this analysis?

Medulloblastoma.WHO.2016.book.chapter.pdf

[jharenza]

@jaclyn-taroni I only looked through this briefly, but looks like the above are the 3 major genes we want?

[jharenza]

@yiran-guo, below are the normal IDs for the samples included in OpenPBTA: OpenPBTA-allnormal-BSids.txt

[cansavvy]

@jharenza , according to the book chapter you attached, those seem to be the three genes we should look for.

[jharenza]

Per our conversation about subjectiveness of germline filtering and potential to miss/over-assign pathogenicity of TP53 variants when they are of uncertain significance, @jaclyn-taroni and I decided we should close this ticket, as well as #378 and #451.