#790 Part3: adding CNV based subtyping for LGAT

[kgaonkar6]

⚠️ #842 #843 needs to be merged before this PR, 03-subset-cnv-files-LGAT.Rmd and output can be reviewed independently though

Purpose/implementation Section

What scientific question is your analysis addressing?

LGAT subtyping is being revamped as per issue. I'm diving into this with staggered PRs per alteration as:

• SNV #790 Part1: adding new SNV subtypes for LGAT #842
• Fusion #790 Part2: adding Fusion based subtyping for LGAT #843
• CNV #790 Part3: adding CNV based subtyping for LGAT  #845

As per issue we will be subtyping LGAT based on CNV in the following genes:

• LGG, FGFR
  harbors FGFR1 TKD (tyrosine kinase domain tandem duplication)

• LGG, CDKN2A/B
  harbors focal CDKN2A and/or CDKN2B deletion

What was your approach?

I used

• manta pbta-sv-manta.tsv.gz to capture tandem duplication
• consensus seg pbta-cnv-consensus.seg.gz to capture consensus seg CNV region
• consensus annotated consensus_seg_annotated_cn_autosomes.tsv.gz to capture annotated genes per consensus CNV with ploidy

I only keep CNV and SV that overlap within FGFR1 gene since the tandem duplication event is a exon level duplication.

CNV status is saved in lgat-subset/LGAT_cnv_subset.tsv as:

	biospecimen_id	FGFR_DUP_TANDEM	FGFR_DUP	CDKN2A_DEL	CDKN2B_DEL

What GitHub issue does your pull request address?

#790

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

For CDKN2A/B I only used copy_number <=1

> cnv_focal_anno_lgat %>%
   dplyr::filter(gene_symbol %in% c("CDKN2A","CDKN2B")) %>%
   dplyr::pull(copy_number) %>%
   table()

  0   1   2   3 
  2  16 134   6 

For FGFR1 I looked for "tandem duplication" in manta file where it's annotated as "DUP:TANDEM" within FGFR1 gene region that also overlaps tyrosine kinase domain

biospecimen_id	ALT	NAME	hgnc_symbol	FGFR_DUP_TANDEM
BS_3108RS7G	DUP:TANDEM	Pkinase_Tyr	FGFR1	Yes
BS_ETTZM63Y	DUP:TANDEM	Pkinase_Tyr	FGFR1	Yes
BS_R726FKHP	DUP:TANDEM	Pkinase_Tyr	FGFR1	Yes
BS_MW6YMRBJ	DUP:TANDEM	Pkinase_Tyr	FGFR1	Yes

Similar to the SV I also filtered consensus seg CNV within FGFR1 and overlaps tyrosine kinase domain with copy_number >2

biospecimen_id	copy_number	NAME	FGFR_DUP
BS_4G9Y2VC6	3	Pkinase_Tyr	Yes
BS_D6XHKZDZ	3	Pkinase_Tyr	Yes
BS_M2MSWKBC	3	Pkinase_Tyr	Yes
BS_MW6YMRBJ	3	Pkinase_Tyr	Yes
BS_V79WFJ6N	3	Pkinase_Tyr	Yes

Which areas should receive a particularly close look?

Is there anything that you want to discuss further?

I did look at exons that overlap the manta/ consensus seg calls that are within FGFR1 and it seems 4 biospecimens with tandem duplication and 5 biospecimens with duplication have exon overlap between 10 and 18.

There are a few calls that overlap <10 exons but it seems from the check that all 4 biospecimens with tandem duplication in FGFR1 and 5 biospecimens with duplication in FGFR1 have atleast 1 SV/CNV overlap where all exons are between 10 and 18.

Let me know if we need more checks on this

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)?

table

What is your summary of the results?

FGFR_DUP_TANDEM = 4
FGFR_DUP = 5
BS_MW6YMRBJ is annotated with a tandem duplication(SV) as well as duplication(CNV)

CDKN2A_DEL = 54
CDKN2B_DEL = 54

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.

[kgaonkar6]

Closing this because unwanted tp53-classifier-score files got added to this PR