MB SHH subtyping

[rjcorb]

Purpose/implementation Section

What scientific question is your analysis addressing?

Closes #564. This PR pulls all molecular alterations associated with specific Medulloblastoma SHH subtypes in all MB SHH samples, and classifies samples first based on methylation subtyping and then by age and molecular criteria from this review

What was your approach?

SHH subtypes are currently classified based on the following criteria:

• SHH-alpha: SHH alpha by methylation OR (>3 years AND (MYCN OR GLI2 amplification OR TPM>=2 OR chr17p loss)
• SHH-delta: SHH delta by methylation OR (no methylation subtype AND (TERT promoter AND DDX3X mutations) OR (>5 years AND (TERT OR DDX3X mutations))
• SHH-beta: SHH-beta by methylation OR (<5 years AND (KMT2D mutations OR PTEN loss/deletion OR PTEN TPM<-2 OR chr2 gain))

There are currently no additional criteria to classify samples as SHH-gamma

What GitHub issue does your pull request address?

564

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

Which areas should receive a particularly close look?

Please review all code and specifically the logic to classify subtypes. Is this consistent with the literature? Are there other molecular alterations we should be considering?

Is there anything that you want to discuss further?

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)?

mb_shh_subtype_summary.csv

What is your summary of the results?

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.
• [X] The analytical code is documented and contains comments.

[jharenza]

Adding some comments from discussion with Sebastian:

Major criteria: DNA methylation-based subtyping into alpha, beta, gamma, delta Minor criteria: Alpha: 3-21 yo, TP53 (som/ger), ELP1 (som/ger), MYCN/GLI2/CCND2 (amp), isochromosome 9p, -17p, -3p Beta: <5 yo, SUFU (som/ger), KMT2D, +2, cnLOH 10q Gamma: <5 yo, no +2p Delta: 10-65, >95% U1 snRNA (RNU1–1, RNU1–2, RNU1–3, and RNU1–4), TERT, DDX3X

[jharenza]

hi @rjcorb can you stack the MB PRs on https://github.com/d3b-center/OpenPedCan-analysis/pull/571? I had to remove MM2S code there.

[jharenza]

hi @rjcorb I haven't pulled this up, but I suspect the error you have is perhaps due needing to unzip the file in R before pulling up the file, since it is only available in zip format in the release. There is a way to read in and unzip contents so you can pull that file.

Error: '/github/workspace/data/cnv-consensus-gistic/broad_values_by_arm.txt' does not exist.

[rjcorb]

@jharenza thanks, this should be resolved now