v12 epn subtyping (3/N)

[ewafula]

Purpose/implementation Section

Purpose/implementation Section

What scientific question is your analysis addressing?

This PR runs EPN subtyping for v12

What was your approach?

Made the following changes:

• Updated script 01 to that assigns disease groups to include high-confidence methylation EPN subtypes from the histologies base file
• updated gene symbols utilized within the module to Gencode v39

NEW	OLD
EZHIP	CXorf67
H3-3A	H3F3A
H3-3B	H3F3B
H3C2	HIST1H3B
H3C3	HIST1H3C
H3C14	HIST2H3C
ZFTA	C11orf95

• excluded the following gene fusions that are no longer required

LTBP3--RELA 
ZTFA--YAP1

• Kept subtyping as was previously performed (i.e., gene expression and scoring gene fusions, focal cnv, etc. ) but assigned EPN subgroups from methylation classification where subgroups have not been determined (i.e., EPN, To be classified).
• README updated.

What GitHub issue does your pull request address?

Part of the v12 release

Directions for reviewers. Tell potential reviewers what kind of feedback you are soliciting.

Which areas should receive a particularly close look?

Please review scripts 01, 02, and 03 in detail to check if they capture everything accurately and logic is correct.

Is there anything that you want to discuss further?

NA

Is the analysis in a mature enough form that the resulting figure(s) and/or table(s) are ready for review?

Yes

Results

What types of results are included (e.g., table, figure)?

Updates EPN subgroups table output.

What is your summary of the results?

612 EPN bs ids (DNA = =212, RNA == 193, and Methly = = 207)
230 patients
398 tumors subtyped:

 subgroup                  n
   <chr>                 <int>
 1 EPN, PF A               267
 2 EPN, PF B                 9
 3 EPN, PF SE                1
 4 EPN, SP                  29
 5 EPN, SP-MYCN              2
 6 EPN, SP-SE B              1
 7 EPN, ST YAP1              8
 8 EPN, ST ZFTA             81
 9 EPN, To be classified    61
10 N/A                      10
> 

Reproducibility Checklist

• The dependencies required to run the code in this pull request have been added to the project Dockerfile.
• This analysis has been added to continuous integration.

Documentation Checklist

• This analysis module has a README and it is up to date.
• This analysis is recorded in the table in analyses/README.md and the entry is up to date.
• The analytical code is documented and contains comments.

[rjcorb]

The code for spinal subtyping in lines 74-76 of 03-summary.Rmdneeds to be changed to:

EPN_final <- EPN_final %>%
  mutate(subgroup = ifelse(disease_group == "spinal" & grepl("amplification", consensus_focal_CN_MYCN), "EPN, SP-MYCN", 
                           ifelse(disease_group == "spinal", "EPN, SP", subgroup)))

the current ifelse statement that specifies consensus_focal_CN_MYCN == "amplification" is the cause of NAs in the final subgroup column. This was probably an oversight on my part when I added the spinal classification a few months ago! Otherwise, everything looks good to me.

[ewafula]

@rjcorb and @zzgeng , I have made the review changes you recommended. Ready for you to check again.

[zzgeng]

Everything works fine and logic is solid. Approving!

[jharenza]

@ewafula and @rjcorb : looking at these results, I think we should update the logic for spinal ependymoma:

If spinal and MYCN amp --> EPN, SP-MYCN
If spinal and has methylation classification of SP or MPE, choose the methyl subtype, else --> To be classified.

Saying this because as I am reviewing WHO 2021, the SP subtype is grade 3, while MPE (myxopapillary, also can be in spine) is grade I and I don't want us to mis-classify those up to SP.

Can you make that change?