What are the strands of structural variant breakpoints?
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6.3 years ago
weishwu ▴ 30

I'm trying to use a tool named ShatterSeek to call chromothripsis regions from SV calls. It requires me to list the breakpoint strands for each SV as input. For example, a deletion will be listed as:

11   8540385     11   8541773     DEL       +       -

A duplication is listed as:

14 61896354     14 62061596     DUP       -       +

As for INV, there are two types: head-to-head (5to5, or h2h) and tail-to-tail (3to3, or t2t):

2 36771088      2 75366617  h2hINV       +       +
17 35895909     17 36309972  t2tINV       -       -

The breakpoint strands are "+ -" for all DEL, "- +" for all DUP, "+ +" for all 5to5 INV, and "- -" for all 3to3 INV, as described here: https://github.com/GooglingTheCancerGenome/sv-report/wiki/VCF-output-formats

However I can't find any documentation about how to assign the strands for translocations which can have all possible strand combinations. As described in the VCF format documentation (https://samtools.github.io/hts-specs/VCFv4.2.pdf), the connection orientations of a translocation SV are denoted as:

REF ALT Meaning
s   t[p[    piece extending to the right of p is joined after t
s   t]p]    reverse comp piece extending left of p is joined after t
s   ]p]t    piece extending to the left of p is joined before t
s   [p[t    reverse comp piece extending right of p is joined before t

Does anyone know what the strand combinations are for each of these four types of translocations?

Thanks.

sv vcf • 4.0k views
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Have you been able to find an answer on this? I was wondering the same thing. I was following the logic from svtools in how they assign internal strandness together with vcf specs and thought this: t[p[ + - t]p] + + ]p]t - + [p[t - - Deletion + - (provided in Shatterseek docs) Tandem dup - + (provided) Insertion + - (unsure?) This is assuming the breakend in the 5' region is + (head) and 3' region is - (tail). It would be ideal to confirm this before using the tool though. Any help would be greatly appreciated, thank you in advance!

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4.0 years ago
trausch ★ 1.9k

I am not sure about other tools but delly outputs INFO/CT which captures the orientation of SV breakpoints. The mapping of SV breakpoints to potential fusion genes is explained here.

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Dear trausch, Many thanks for you reply. Your reply reminded me that I may not be able to treat the SV input required by shatterseek as BEDPE format (in fact, I thought so, because the example attached with shatterseek is very similar to the bedpe format), but I still don’t know how to convert vcf accurately for the proper format, the shatterseek tutorial (https://github.com/parklab/ShatterSeek/blob/master/tutorial.pdf) are very confusing. Do you have some suggestions.

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4.0 years ago
octpus616 ▴ 120

Dear weishwu, Happy to see this topic, I meet the samle problem recently. I am tried the tool called svtools noticed by renny, But I find the translocation SV seems incorrectly after convert. Could you please share me some information. Best. Zhang

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