Add filter for non-synonymous mutations and re-run TMB with bug fix #728

cansavvy · 2020-07-13T21:30:47Z

Purpose/implementation Section

What scientific question is your analysis addressing?

Adding an option to drop the synonymous mutations from the TMB calculations.
Re-running downstream TMB items after getting them updated.

I would like to do some more in depth comparison of the old and new results, but I will save that for a different PR so as to not have too many things at once.

What was your approach?

Added a filtering option --nonsynfilter which is a TRUE/FALSE on whether mutations should be filtered to be only non-synonymous mutations.
I re-ran both TCGA and PBTA TMBs
I re-ran the tmb-compare-notebook and adjusted some of the margins so it would be better aligned.
I re-ran the fig2-mutational-landscape.R figure again so it's updated.

What GitHub issue does your pull request address?

#726

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

Is there a way I can make the margins adjust more automatically? It was quite a bit of finagling of margins and text size to get the plots to be aligned. Perhaps this is just how it has to be.
Anything I'm missing?

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

Yes. The TMBs for the adults do seem slightly higher? That's good.

Results

What is your summary of the results?

Still figuring this out. It's not changed as I suspected it would be.
*Note that data files themselves are not pushed to GitHub but we will need to update them in the next data release.

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.

add folder for notebooks

add gitignore

update output file path handle in get-tcga-capture_kit.py

add boxplot.R

skip the manifest header

add ci for tcga-capture-kit-investigation

…hub.com/yuankunzhu/OpenPBTA-analysis into tcga-tmb-qc

Merge branch 'analyses/tcga-capture-kit-investigation' of https://github.com/yuankunzhu/OpenPBTA-analysis into Teja_tmbQC

…vestigation.sh script

…paths

Co-Authored-By: jashapiro <[email protected]>

cansavvy · 2020-07-14T14:14:14Z

This is a reminder to myself to update the blog post with these updates to TMB. @cansavvy

jashapiro

This looks great. Do we want to include a version without the nonsyn filter as well, just for comparison? I would not put that in the final figure, but having the figure and/or data table might be nice.

As to your question about margins, I might try (if you have not already) assembling the plot with patchwork or cowplot, both of which tend to handle adjusting parameters to make the grids line up pretty automatically.

jashapiro · 2020-07-14T14:32:12Z

analyses/snv-callers/scripts/03-calculate_tmb.R

+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"
+)


As we have discussed, this does differ slightly from the standard proposed in https://jitc.bmj.com/content/8/1/e000147#DC by the Friends of Cancer Research TMB Harmonization Project.

The relevant table is here: #725 (comment)

In particular, the FoCR group does not include Translation_Start_Site, Nonstop_Mutation or Splice_Site. I tend to think all of those are worth including, but I guess one simple question is how common these mutations actually are in the data set. Either way, we will want to standardize our criteria across analyses.

I think this question is something I can ask in a next PR that does some more exploration. I'll file an issue that lays out what kinds of exploration analyses I think should be included.

Filed the issue: #729

cansavvy · 2020-07-14T15:33:30Z

This looks great. Do we want to include a version without the nonsyn filter as well, just for comparison? I would not put that in the final figure, but having the figure and/or data table might be nice.

I want to do this, but figured I should make it a separate PR so this one stays focused.

cansavvy · 2020-07-14T15:48:56Z

The follow up questions, I'll address on separate PRs, notoed on this issue here: #729

For wrapping up this current PR, I'll play around a bit with finding a better way to "automagically" align the tmb plots.

cansavvy · 2020-07-14T16:11:02Z

I tried patchwork. But am encountering an error like what's documented here: thomasp85/patchwork#148
I tried minimizing the theme arguments specified but it still didn't fix the problem.

cansavvy · 2020-07-14T16:14:35Z

@jashapiro I actually use cowplot in the tmb-compare-tcga notebook, but for whatever reason the align = "v" argument doesn't work. Let me know if you have insight into why its broken/being ignored by cowplot: https://github.com/AlexsLemonade/OpenPBTA-analysis/blob/master/analyses/tmb-compare-tcga/compare-tmb.Rmd#L141

cansavvy · 2020-07-15T17:37:58Z

Not sure what else to try for the "automagic" y axis alignment (see above comments). But in the interest of moving this and the future issues (#729) forward, I've wrote this problem down here: cansavvy/openpbta-notebook-concept#9 and will return to it if we have any breakthroughs.

With this being noted, are we ready to merge, @jashapiro ?

jashapiro · 2020-07-15T17:41:53Z

With this being noted, are we ready to merge, @jashapiro ?

yuankunzhu and others added 30 commits March 4, 2020 00:22

✨ add investigation on the tcga capture kit

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📝 add comments for scripts/intersect-bed-maf.sh

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🎨 remove analyses folder name

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📝 add coverage-comparison

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🎨 add folder for notebooks

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add folder for notebooks

🎨 move ipynb to notebooks folder

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🎨 remove pbta-tcga-manifest.tsv

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📝 add links to notebooks; fix wording

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Merge branch 'master' into analyses/tcga-capture-kit-investigation

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Adding coverage for TCGA BED

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Adding target old and new coverage for TCAG BED

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Merge remote-tracking branch 'upstream/master' into tcga-tmb-qc

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✨ add gitignore

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add gitignore

⚡ update output file path handle in get-tcga-capture_kit.py

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update output file path handle in get-tcga-capture_kit.py

Adding script for hg19 to Gh38 using CrossMap

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✨ add boxplot.R

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add boxplot.R

🐛 skip the manifest header

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skip the manifest header

✨ add ci for tcga-capture-kit-investigation

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add ci for tcga-capture-kit-investigation

Merge remote-tracking branch 'upstream/master' into tcga-tmb-qc

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Merge branch 'analyses/tcga-capture-kit-investigation' of https://git…

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…hub.com/yuankunzhu/OpenPBTA-analysis into tcga-tmb-qc

git pull all changes YUankun submitted on 03-05-2020

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Merge branch 'analyses/tcga-capture-kit-investigation' of https://github.com/yuankunzhu/OpenPBTA-analysis into Teja_tmbQC

Added coverage plot

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Added coverage plot

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Added crossmap, fixed run_investigation and moved coverage to /plots

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Removed CrossMapBED.sh script since all of the commands are in run_in…

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…vestigation.sh script

Changed WORKING_DIR in run-investigation and all other corresponding …

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…paths

Changed BED names in intersect-bed-maf.sh

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Updated READ.md files

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Updated READ.md file

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Update analyses/tcga-capture-kit-investigation/README.md

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Co-Authored-By: jashapiro <[email protected]>

cansavvy added 3 commits July 13, 2020 15:54

Add Variant Classification filter

3707b3b

Add nonsynfilter to bash scripts

cffd235

Add a space

cc63ee2

cansavvy changed the title ~~Add filter for non-synonymous mutations and re-run TMB with bug fix~~ WIP: Add filter for non-synonymous mutations and re-run TMB with bug fix Jul 13, 2020

cansavvy added the work in progress Used to label (non-draft) pull requests that are not yet ready for review label Jul 13, 2020

cansavvy added 2 commits July 13, 2020 17:32

Re-run TMB compare as well

d5ada61

Adjust plots and re-run the figures/ version

53b6f95

cansavvy marked this pull request as ready for review July 14, 2020 13:51

cansavvy changed the title ~~WIP: Add filter for non-synonymous mutations and re-run TMB with bug fix~~ Add filter for non-synonymous mutations and re-run TMB with bug fix Jul 14, 2020

Adjust the y scale

de600f5

cansavvy requested a review from jashapiro July 14, 2020 14:06

cansavvy removed the work in progress Used to label (non-draft) pull requests that are not yet ready for review label Jul 14, 2020

Merge branch 'master' into cansavvy/non-syn-filter

62958eb

jashapiro reviewed Jul 14, 2020

View reviewed changes

cansavvy mentioned this pull request Jul 14, 2020

Exploratory Side Analysis: Variant_Classification breakdown #729

Closed

cansavvy mentioned this pull request Jul 15, 2020

FIgure out how to make margins fix and y axis of TMB plot align "automagically" cansavvy/openpbta-notebook-concept#9

Open

jashapiro approved these changes Jul 15, 2020

View reviewed changes

jashapiro merged commit 9b44bf1 into AlexsLemonade:master Jul 15, 2020

cansavvy mentioned this pull request Aug 20, 2020

Explore Variant_Classification's Impact on TMB: Part 1: Filter vs no Filter #739

Merged

5 tasks

cansavvy mentioned this pull request Sep 3, 2020

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

Closed

cansavvy deleted the cansavvy/non-syn-filter branch September 8, 2020 18:24

cansavvy mentioned this pull request Sep 11, 2020

Planned Data Release: V17 #732

Closed

jaclyn-taroni mentioned this pull request Sep 11, 2020

v17-Release #764

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Add filter for non-synonymous mutations and re-run TMB with bug fix #728

Add filter for non-synonymous mutations and re-run TMB with bug fix #728

cansavvy commented Jul 13, 2020 •

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jashapiro commented Jul 15, 2020

Add filter for non-synonymous mutations and re-run TMB with bug fix #728

Add filter for non-synonymous mutations and re-run TMB with bug fix #728

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cansavvy commented Jul 13, 2020 • edited Loading

Purpose/implementation Section

What scientific question is your analysis addressing?

What was your approach?

What GitHub issue does your pull request address?

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

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

Results

What is your summary of the results?

Reproducibility Checklist

Documentation Checklist

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