sjspielman
commented
1 year ago I know this PR is still in progress since a table needs to be added, as discussed on Slack, but wanted to leave a note to that end @jharenza -
I see you've fixed the not-so-great bug where 06-TERTp-EXTENDScores.R never got added into RUN-telomerase-activity-prediction.sh here: https://github.com/AlexsLemonade/OpenPBTA-analysis/blob/ae299d9e1ff1c270e5198d8aa0bdff4f1fad1727/analyses/telomerase-activity-prediction/RUN-telomerase-activity-prediction.sh#L54, so that’s good!
But! The way that the module script logic is written, 06-TERTp-EXTENDScores.R will not get run as part of the manuscript run - even if there were no bug here, 06-TERTp-EXTENDScores.R would not have been run anyways over in #1672. So, if we want to make a table that is used in the MS, we have to make a choice here. We can either:
- We keep the logic in
RUN-telomerase-activity-prediction.shas is, and actually make that table over intables/. - Move the code that runs
06-TERTp-EXTENDScores.Rout of theif/elselogic entirely so that it always runs when the module is run. But, as I write this, thinking we should move this line out of the if/else either way.
jharenza
Purpose/implementation Section
What scientific question is your analysis addressing?
This addresses part of the reviewer comment asking how telomerase scores are related to TERT rearrangements or mutations. My eyes must have glazed past "rearrangements" in the review, so here, I am adding the TERT SVs for assessment.
What was your approach?
Since SVs are often difficult to assess pathogenicity for, I took a very conservative approach here. I found knotAnnotSV, a companion tool to AnnotSV, which helps asses function of SVs, including ACMG pathogenicity call. To use this, I had to create a BED file from manta SV, plug it into https://lbgi.fr/AnnotSV, then assessed the calls for ACMG == 4|5, which correspond to likely pathogenic (LP) or pathogenic (P).
What GitHub issue does your pull request address?
NA, revision
Directions for reviewers. Tell potential reviewers what kind of feedback you are soliciting.
Which areas should receive a particularly close look?
NA
Is there anything that you want to discuss further?
Note: I reran the whole module, but realized later I maybe should have just run script 06, which, oddly wasn't in the shell script so I added it. Not sure if that was not added on purpose.
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)?
What is your summary of the results?
There were 2 samples with LP TERT SVs (of 3 with a TERT SV). There were also multiple SVs overlapping TERT or subsuming TERT (eg large arm deletions), and although knotAnnotSV often annotated these full-length SVs as P/LP, I do not think we can confidently say these are "TERT" SVs unless a breakpoint is actually in TERT. So, I collected these in the BED file, but did not associate them with being TERT-driven.
The 2 samples with LP TERT SVs correspond to two sample ids from 2 patients. The corresponding RNAs are both polyA, so I did not end up plotting / combining these in any way with the TERTp mutations.
In summary, while the EXTEND paper shows a nice plot of higher scores in TERT-rearranged tumors, we don't have the power to assess that here and we can refer back to the paper for association.
I really wanted to just cover bases and check SVs here and note this in the script.
Reproducibility Checklist
Documentation Checklist
READMEand it is up to date.analyses/README.mdand the entry is up to date.