Annotating BND events - INV and TRA

[vandrioletti-art]

Hi @lgmgeo ,

First, tahnks for the great tool.

I am using the version 3.5.10.

I am starting testing it on Dragen outcomes and I have few doubts still unresolved. My test case is made of Inversions and Translocations (a mix of benign and pathogenic), which are represented as follows:

• reciprocal inversion

chr2	38121110	DRAGEN:BND:126718:0:1:0:0:0:0	C	G]chr2:47669522]	999	PASS	SVTYPE=BND;MATEID=DRAGEN:BND:126718:0:1:0:0:0:1	GT:GQ:PL:PR:SR:SB:FS:VF    0/1:999:999,0,999:64,29:48,16:24,24,0,16:37.390:88,45
chr2	38121111	DRAGEN:BND:126718:0:1:1:0:0:0	T	[chr2:47669523[T	999	PASS	SVTYPE=BND;MATEID=DRAGEN:BND:126718:0:1:1:0:0:1	GT:GQ:PL:PR:SR:SB:FS:VF    0/1:999:999,0,999:65,25:48,19:24,24,18,1:32.535:88,43
chr2	47669521	DRAGEN:BND:126718:0:1:0:0:0:1	C	T]chr2:38121111]	999	PASS	SVTYPE=BND;MATEID=DRAGEN:BND:126718:0:1:0:0:0:0	GT:GQ:PL:PR:SR:SB:FS:VF    0/1:999:999,0,999:64,29:48,16:24,24,0,16:37.390:88,45
chr2	47669522	DRAGEN:BND:126718:0:1:1:0:0:1	A	[chr2:38121112[A	999	PASS	SVTYPE=BND;MATEID=DRAGEN:BND:126718:0:1:1:0:0:0	GT:GQ:PL:PR:SR:SB:FS:VF    0/1:999:999,0,999:65,25:48,19:24,24,18,1:32.535:88,43

• small inversion (contained in reads)

chr4    144359319   DRAGEN:INV:1:0:0:0  TTGACTCCAGCCTTTATAACCTGCCCAGGAGTTATTCCCATGATGTTTTACCAAAGGTGTCTCCATCAAGT <INV>   82  PASS    END=144359389;SVTYPE=INV;SVLEN=-70;CIGAR=1M70I70D;CONTIG=TACTTGATGGAGACACCTTTGGTAAAACATCATGGGAATAACTCCTGGGCAGGTTATAAAGGCTGGAGTCACA;CIPOS=0,2;HOMLEN=2;HOMSEQ=TG;   GT:FT:GQ:PL:PR:SR:SB:FS:VF   0/1:PASS:82:132,0,999:48,0:130,12:50,80,11,1:0.000:131,12

• translocation

chr7	152402130	DRAGEN:BND:TOY002:0:0:0:0:0:0	C	C[chr21:10415010[	999	PASS	SVTYPE=BND;MATEID=DRAGEN:BND:TOY002:0:0:0:0:0:1;EVENT=DRAGEN:BND:TOY002:0:0:0:0:0:0;BND_DEPTH=88;MATE_BND_DEPTH=91	GT:FT:GQ:PL:PR:SR	1/1:PASS:99:999,999,0:0,63:0,58
chr7	152402134	DRAGEN:BND:TOY002:1:0:0:0:0:0	A	A[chr21:10415016[	999	PASS	SVTYPE=BND;MATEID=DRAGEN:BND:TOY002:1:0:0:0:0:1;EVENT=DRAGEN:BND:TOY002:0:0:0:0:0:0;BND_DEPTH=85;MATE_BND_DEPTH=89	GT:FT:GQ:PL:PR:SR	1/1:PASS:99:999,999,0:0,60:0,55
chr21	10415010	DRAGEN:BND:TOY002:0:0:0:0:0:1	C	]chr7:152402130]C	999	PASS	SVTYPE=BND;MATEID=DRAGEN:BND:TOY002:0:0:0:0:0:0;EVENT=DRAGEN:BND:TOY002:0:0:0:0:0:0;BND_DEPTH=91;MATE_BND_DEPTH=88	GT:FT:GQ:PL:PR:SR	1/1:PASS:99:999,999,0:0,58:0,63
chr21	10415016	DRAGEN:BND:TOY002:1:0:0:0:0:1	G	]chr7:152402134]G	999	PASS	SVTYPE=BND;MATEID=DRAGEN:BND:TOY002:1:0:0:0:0:0;EVENT=DRAGEN:BND:TOY002:0:0:0:0:0:0;BND_DEPTH=89;MATE_BND_DEPTH=85	GT:FT:GQ:PL:PR:SR	1/1:PASS:99:999,999,0:0,55:0,60

My questions are:

• will these BNDs be recognised as single events? If now, how can I reach a "single-event" annotation?
• can I build a custom resource with selected clinvar and gnomad translocations and inversions records? How should this resource be?
• how is the match to a custom resource managed? Can I control the overlap? Do you have any suggestion?

Thank you!

Valentina

[lgmgeo]

will these BNDs be recognised as single events? If no, how can I reach a "single-event" annotation?

• The INV seems OK.

• I am quite surprised to see the reciprocal inversion described on 4 lines (it should be on 2 lines or ideally 1 single line).
  My advice is to use variant-extractor developed by @Rapsssito (he's an expert! Asking for his help seems ideal to me)

• The translocation should be described on 2 lines (one for each breakend). AnnotSV annotates each breakend.

can I build a custom resource with selected clinvar and gnomad translocations and inversions records? How should this resource be?

Yes for sure. You need to create a BED file.
Please look at the README (section d) Custom annotations: External BED annotation files (optional))

how is the match to a custom resource managed? Can I control the overlap? Do you have any suggestion?

Different possibilities are proposed:

• FtIncludedInSV (with Ft for Feature)
  By default, the “overlap” option is set to 100%. This option can be used to change this setting.
  You will find all the information in the README.
• SVincludedInFt
• AnyOverlap

Suggestions:

• For INV: create a BED file "chrom start end ID"
• For TRA: create a BED file with each breakend of the TRA:
  "chrom1 pos1 pos1+1"
  "chrom2 pos2 pos2+1"
  To be less stringent, you can use a confidence interval around each breakend during the BED creation, e.g. "chrom1 pos1-10 pos1+11"
  Then use the AnyOverlap directory to match your annotation.
  Don't forget to start your BED file with a first line beginning with a “#” and describing the header of your new annotations.

[vandrioletti-art]

Thank you @lgmgeo !

I'll test your suggestions.

[lgmgeo]

Feel free to leave feedback here later for other users ;o)

[lgmgeo]

EUCANCan/variant-extractor#6