BND representation

Hi @fritzsedlazeck ,

I noticed that Sniffles now reports BND as default for translocation, instead of TRA in VCF. Thank you for the modification! I like the BND representation more, as is is clearly described in the VCF v4.2 the spec: https://samtools.github.io/hts-specs/VCFv4.2.pdf

I found that for some cases (STRANDS=++ and --), BND representation in Sniffles’ VCF is not following the VCF v4.2. Also, the VCF spec specifies that two BND entries should appear in VCF with MATEID for a simple translocation, instead of using one BND entry with “STRANDS=XX”. It would be great if you could consider modifying the BND representation (multiple BND entries for one TRA, using MATEID, instead of STRAND=XX), so that it complies more with the VCF spec.

Just to clarify, I pasted some TRA predictions with Sniffles vs. Manta v1.5.0. Please note that I used publicly available PacBio data data for Sniffles and Illumina data for Manta (both of SKBR3), so the predicted SV positions may not match exactly (but I assume two predictions refer to the same SV). With these examples, I’m trying to convince you that the Manta BND representation (below) would comply more with the VCF spec.

• Case: +/+ Sniffles chr4 119878405 33216 N N[chr8:43843855[ . PASS PRECISE;SVMETHOD=Snifflesv1.0.9;ZMW=29;STD_quant_start=0.462910;STD_quant_stop=0.597614;Kurtosis_quant_start=5.012614;Kurtosis_quant_stop=8.825857;SVTYPE=BND;SUPTYPE=SR;SVLEN=0;STRANDS=++;RE=29 GT:DR:DV ./.:.:29

Manta chr4 119878405 MantaBND:68981:0:1:0:0:0:0 T T]chr8:43843854] . PASS SVTYPE=BND;MATEID=MantaBND:68981:0:1:0:0:0:1;SOMATIC;SOMATICSCORE=127;BND_DEPTH=52;MATE_BND_DEPTH=56 PR:SR 85,0:72,0 43,14:51,17 chr8 43843854 MantaBND:68981:0:1:0:0:0:1 A A]chr4:119878405] . PASS SVTYPE=BND;MATEID=MantaBND:68981:0:1:0:0:0:0;SOMATIC;SOMATICSCORE=127;BND_DEPTH=56;MATE_BND_DEPTH=52 PR:SR 85,0:72,0 43,14:51,17

• Case: +/- Sniffles chr1 229218656 32965 N N[chr5:138549260[ . PASS PRECISE;SVMETHOD=Snifflesv1.0.9;ZMW=26;STD_quant_start=0.620174;STD_quant_stop=0.554700;Kurtosis_quant_start=4.621364;Kurtosis_quant_stop=3.680843;SVTYPE=BND;SUPTYPE=SR;SVLEN=0;STRANDS=+-;RE=26 GT:DR:DV ./.:.:26

Manta chr1 229218656 MantaBND:18921:0:1:0:0:0:1 G GC[chr5:138549260[ . PASS SVTYPE=BND;MATEID=MantaBND:18921:0:1:0:0:0:0;SVINSLEN=1;SVINSSEQ=C;SOMATIC;SOMATICSCORE=133;BND_DEPTH=70;MATE_BND_DEPTH=60 PR:SR 81,0:88,0 41,18:77,18 chr5 138549260 MantaBND:18921:0:1:0:0:0:0 T ]chr1:229218656]CT . PASS SVTYPE=BND;MATEID=MantaBND:18921:0:1:0:0:0:1;SVINSLEN=1;SVINSSEQ=C;SOMATIC;SOMATICSCORE=133;BND_DEPTH=60;MATE_BND_DEPTH=70 PR:SR 81,0:88,0 41,18:77,18

• Case: -/+ Sniffles chr3 141644031 33135 N ]chr8:88792669]N . PASS PRECISE;SVMETHOD=Snifflesv1.0.9;ZMW=37;STD_quant_start=0.000000;STD_quant_stop=0.235702;Kurtosis_quant_start=7.512962;Kurtosis_quant_stop=13.846639;SVTYPE=BND;SUPTYPE=SR;SVLEN=0;STRANDS=-+;RE=37 GT:DR:DV ./.:.:37

Manta chr3 141644031 MantaBND:53870:0:1:0:1:0:0 T ]chr8:88792669]T . PASS SVTYPE=BND;MATEID=MantaBND:53870:0:1:0:1:0:1;SOMATIC;SOMATICSCORE=71;BND_DEPTH=51;MATE_BND_DEPTH=45 PR:SR 99,0:63,0 167,23:338,23 chr8 88792669 MantaBND:53870:0:1:0:1:0:1 A A[chr3:141644031[ . PASS SVTYPE=BND;MATEID=MantaBND:53870:0:1:0:1:0:0;SOMATIC;SOMATICSCORE=71;BND_DEPTH=45;MATE_BND_DEPTH=51 PR:SR 99,0:63,0 167,23:338,23

• Case: -/- Sniffles chr4 87565959 33204 N ]chr19:58533693]N . PASS PRECISE;SVMETHOD=Snifflesv1.0.9;ZMW=10;STD_quant_start=1.760682;STD_quant_stop=0.836660;Kurtosis_quant_start=-0.429761 ;Kurtosis_quant_stop=0.877551;SVTYPE=BND;SUPTYPE=SR;SVLEN=0;STRANDS=--;RE=10 GT:DR:DV ./.:.:10

Manta chr4 87565959 MantaBND:66424:0:1:0:1:0:0 T [chr19:58533694[T . PASS SVTYPE=BND;MATEID=MantaBND:66424:0:1:0:1:0:1;CIPOS=0,1;HOMLEN=1;HOMSEQ=T;SOMATIC;SOMATICSCORE=72;BND_DEPTH=51;MATE_BND_DEPTH=58 PR:SR 86,0:85,0 32,7:50,8 chr19 58533693 MantaBND:66424:0:1:0:1:0:1 A [chr4:87565960[A . PASS SVTYPE=BND;MATEID=MantaBND:66424:0:1:0:1:0:0;CIPOS=0,1;HOMLEN=1;HOMSEQ=C;SOMATIC;SOMATICSCORE=72;BND_DEPTH=58;MATE_BND_DEPTH=51 PR:SR 86,0:85,0 32,7:50,8

Thank you for taking a look!

[vmukhina]

Hi @fritzsedlazeck , this problem is still actual in new sniffles versions. I tested 2.0.2 and 2.0.7 and both give me BND representation without mateid like chr1 8595284 Sniffles2.BND.B7B6S0 N ]chr14:87478116]N 60 PASS PRECISE;SVTYPE=BND;SUPPORT=6;COVERAGE=30,26,33,34,32;STRAND=±;NM=0.060;AF=0.194;CHR2=chr14;STDEV_POS=1.732 GT:GQ:DR:DV 0/0:9:25:6 I also don’t see any complementary entries in files and there are no MATEID flags at all. Please let me know if there is another version with fix. Thanks!

[fritzsedlazeck]

We just pushed a completely new version of Sniffles (v2.0.0.2) and hope this will be resolved.