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Updated analysis: filter to only non-synonymous mutations for TMB #726

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jashapiro opened this issue Jul 13, 2020 · 1 comment
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@jashapiro
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What analysis module should be updated and why?

snv-callers, specifically
https://github.com/AlexsLemonade/OpenPBTA-analysis/blob/master/analyses/snv-callers/scripts/03-calculate_tmb.R
and
https://github.com/AlexsLemonade/OpenPBTA-analysis/blob/master/analyses/snv-callers/util/tmb_functions.R

What changes need to be made? Please provide enough detail for another participant to make the update.

Currently, the TMB we are using for comparisons includes all mutations in coding regions (with the caveat that there currently a bug as described in #724). To better conform with emerging standards, as implemented in #725, we should update our TMB calculations to use only the following non-synonymous changes:
Missense_Mutation
In_Frame_Del
Nonsense_Mutation
In_Frame_Ins
Frame_Shift_Del
Frame_Shift_Ins

One note, is that this list of non-synonymous mutation types is slightly shorter than the one used in MAFtools, and implemented here:

# Variant Classification with High/Moderate variant consequences from maftools
nonsynonymous <- c(
"Missense_Mutation",
"Frame_Shift_Del",
"In_Frame_Ins",
"Frame_Shift_Ins",
"Splice_Site",
"Nonsense_Mutation",
"In_Frame_Del",
"Nonstop_Mutation",
"Translation_Start_Site"
)

We should probably standardize these two.

This change can be implemented by adding a dplyr::filter() step here:


It is likely that we will want to make this optional in the enclosing function.

What input data should be used? Which data were used in the version being updated?

Input data is the same as previously.

When do you expect the revised analysis will be completed?

The actual changes are small and should be quick. Downstream consequences may take longer to sort out.

Who will complete the updated analysis?

TBD; could be implemented alongside the changes to fix #724, as both will require updating of downstream analyses, and we may not want to do that more than once!

@cansavvy
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cansavvy commented Sep 3, 2020

Now that #728 and #739 have been merged, I think this can be closed.

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