HDR regions not included in coresyn calls, but still present in filtered VCF

[mparker2]

Hi @lrauschning,

when I run msyd call in --core mode on some potato haplotypes, I get a nice PFF file of the coresyn regions and a merged VCF for the same coresyn. The SNPs and indels which do not overlap coresyn regions are nicely filtered out, which is exactly what I want.

Msyd breaks the coresyn regions on HDRs. I don't know if @mnshgl0110 would agree with this, since HDRs are considered as part of a syntenic region by syri, but it works quite nicely for me. I want to get rid of them for my current analysis. However, they are not filtered out in the VCF. This doesn't seem quite correct... imo either the PFF should include the HDR regions as coresyn (and the VCF include them), or they should be filtered out of the VCF.

What is your opinion?

[lrauschning]

Hiya,
nice to see the VCF filtering (mostly) works!
The reason HDR regions break coresyn is that they do not have corresponding SYNAL annotations, which is what (the current iteration of) msyd works on so that we can have exact alignments with basepair precision.
I think the HDRs might be retained because they start right before/after a coresyn region, and we fetch all variants intersecting a multisyn (end-inclusive) for reporting in the merged VCF.
If you just want the snps, not passing -x/--complex should filter out any VCF records with symbolic alleles incl. HDRs.
Other than that, grep -v HDR would be a quick workaround. Might be worth adding a CLI option to restrict merging to records strictly within a multisyn, though.

[mparker2]

That makes sense. Using --complex is not a foolproof solution because syri is able to create VCFs with both symbolic or full sequence alleles (using --hdrseq)

[lrauschning]

Ah, true.
Then I'll look into adding a CLI option for strictly contained records.
I think filtering for specific types of records is probablybest left to the user, though.

[mparker2]

Hey Leon, related question not worth its own thread... you said you use the SYNAL annotations not SYN for basepair level alignment. How do you deal with the fact that syri records the parents of SNPs/Indels using the SYN and not the SYNAL records? I'm trying to write a script to build chain files from syri/msyd output and I'm finding it quite frustrating to determine because SYNALs can overlap each other and have different indels at the same/adjacent positions

[lrauschning]

Sorry, a lot of things last week and this slipped through the cracks.
Yes, this was a major annoyance with msyd, too.
Msyd is not using the annotations of any small variants, the filtering is only location based.
Overlapping SYNALs are cut until they are no longer overlapping, from the top of my head the overlapping sequence is cut from the latter SYNAL record.
Another issue that I only fixed last summer is that sometimes SYNALs contain very long deletions/insertions (in AMPRIL I saw up to 4 kb). SYNALs are split on these long breaks now and treated as separate for each part of it.

[lrauschning]

Also finally added that option for filtering for strictly contained regions :)