MNP handling in version 1.0.9

[marc-sturm]

Hi,

I have a question about MNP handling in 1.0.9.

I created the following minmal test VCF:

##fileformat=VCFv4.2
##fileDate=20231214
##source=freeBayes v1.3.6
##reference=/tmp/local_ngs_data_GRCh38//GRCh38.fa
##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">
##FORMAT=<ID=GQ,Number=1,Type=Float,Description="Genotype Quality, the Phred-scaled marginal (or unconditional) probability of the called genotype">
##FORMAT=<ID=DP,Number=1,Type=Integer,Description="Read Depth">
##FORMAT=<ID=AD,Number=R,Type=Integer,Description="Number of observation for each allele">
##FORMAT=<ID=RO,Number=1,Type=Integer,Description="Reference allele observation count">
##FORMAT=<ID=QR,Number=1,Type=Integer,Description="Sum of quality of the reference observations">
##FORMAT=<ID=AO,Number=A,Type=Integer,Description="Alternate allele observation count">
##FORMAT=<ID=QA,Number=A,Type=Integer,Description="Sum of quality of the alternate observations">
##FORMAT=<ID=GL,Number=G,Type=Float,Description="Genotype Likelihood, log10-scaled likelihoods of the data given the called genotype for each possible genotype generated from the reference and alternate alleles given the sample ploidy">
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO	FORMAT	vc_freebayes_in
chr22	11066446	.	G	A	5700.41	.	.	GT:GQ:DP:AD:RO:QR:AO:QA:GL	0/1:160.002:436:198,238:198:7122:238:8563:-588.912,0,-509.596
chr22	11066465	.	TG	CA	4699.45	.	.	GT:GQ:DP:AD:RO:QR:AO:QA:GL	0/1:135.948:455:216,198:216:7876:198:7070:-482.411,0,-583.824

When using vcfallelicprimitives -kg (version 1.0.3), I get the following variants as expected:

#CHROM  POS     ID      REF ALT QUAL FILTER INFO FORMAT vc_freebayes_in
chr22   11066446        . G A 5700.41 . . GT 0/1
chr22   11066465        . T C 4699.45 . LEN=1;TYPE=snp GT 0|1
chr22   11066466        . G A 4699.45 . LEN=1;TYPE=snp GT 0|1

When using vcfallelicprimitives -k (version 1.0.9), the MNP is missing:

#CHROM  POS     ID      REF ALT QUAL FILTER INFO FORMAT vc_freebayes_in
chr22   11066446        . G A 5700.41 . . GT:GQ:DP:AD:RO:QR:AO:QA:GL 0/1:160.002:436:198,238:198:7122:238:8563:-588.912,0,-509.596

I don't understand why it is not in the output.

Since, vcfwave is recommended anyway I tried vcfwave --quiet, but it crashes when processing the MNP:

#CHROM  POS     ID      REF ALT QUAL FILTER INFO FORMAT vc_freebayes_in
chr22   11066446        . G A 5700.41 . . GT:GQ:DP:AD:RO:QR:AO:QA:GL 0/1:160.002:436:198,238:198:7122:238:8563:-588.912,0,-509.596
terminate called after throwing an instance of 'std::out_of_range'
  what():  vector::_M_range_check: __n (which is 0) >= this->size() (which is 0)
Aborted (core dumped)

Any suggestions?

Best,
Marc

[pjotrp]

try legacy vcfallelicprimitives -a SW -kg

[marc-sturm]

The legacy version 1,0.3 works as I said above.

Version 1.0.10 still does not work.

vcfwave --quiet no longer crashes, but does not decompose the MNP:

  ##fileformat=VCFv4.2
  ##fileDate=20231214
  ##source=freeBayes v1.3.6
  ##reference=/tmp/local_ngs_data_GRCh38//GRCh38.fa
  ##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">
  ##FORMAT=<ID=GQ,Number=1,Type=Float,Description="Genotype Quality, the Phred-scaled marginal (or unconditional) probability of the called genotype">
  ##FORMAT=<ID=DP,Number=1,Type=Integer,Description="Read Depth">
  ##FORMAT=<ID=AD,Number=R,Type=Integer,Description="Number of observation for each allele">
  ##FORMAT=<ID=RO,Number=1,Type=Integer,Description="Reference allele observation count">
  ##FORMAT=<ID=QR,Number=1,Type=Integer,Description="Sum of quality of the reference observations">
  ##FORMAT=<ID=AO,Number=A,Type=Integer,Description="Alternate allele observation count">
  ##FORMAT=<ID=QA,Number=A,Type=Integer,Description="Sum of quality of the alternate observations">
  ##FORMAT=<ID=GL,Number=G,Type=Float,Description="Genotype Likelihood, log10-scaled likelihoods of the data given the called genotype for each possible genotype generated from the reference and alternate alleles given the sample ploidy">
  ##INFO=<ID=TYPE,Number=A,Type=String,Description="The type of allele, either snp, mnp, ins, del, or complex.">
  ##INFO=<ID=LEN,Number=A,Type=Integer,Description="allele length">
  ##INFO=<ID=ORIGIN,Number=1,Type=String,Description="Decomposed from a complex record using vcflib vcfwave and alignment with WFA2-lib.">
  ##INFO=<ID=INV,Number=0,Type=Flag,Description="Inversion detected">
  #CHROM  POS     ID      REF     ALT     QUAL    FILTER  INFO    FORMAT  vc_freebayes_in
  chr22   11066446        .       G       A       5700.41 .       .       GT:GQ:DP:AD:RO:QR:AO:QA:GL      0/1:160.002:436:198,238:198:7122:238:8563:-588.912,0,-509.596
  chr22   11066465        ._1     TG      CA      4.7e+03 .       ORIGIN=chr22:11066465;LEN=2;TYPE=mnp    GT      0|1

vcfallelicprimitives -k -a SW still removes the MNP. When using -a WF the MNP is also removed:

##fileformat=VCFv4.2
##fileDate=20231214
##source=freeBayes v1.3.6
##reference=/tmp/local_ngs_data_GRCh38//GRCh38.fa
##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">
##FORMAT=<ID=GQ,Number=1,Type=Float,Description="Genotype Quality, the Phred-scaled marginal (or unconditional) probability of the called genotype">
##FORMAT=<ID=DP,Number=1,Type=Integer,Description="Read Depth">
##FORMAT=<ID=AD,Number=R,Type=Integer,Description="Number of observation for each allele">
##FORMAT=<ID=RO,Number=1,Type=Integer,Description="Reference allele observation count">
##FORMAT=<ID=QR,Number=1,Type=Integer,Description="Sum of quality of the reference observations">
##FORMAT=<ID=AO,Number=A,Type=Integer,Description="Alternate allele observation count">
##FORMAT=<ID=QA,Number=A,Type=Integer,Description="Sum of quality of the alternate observations">
##FORMAT=<ID=GL,Number=G,Type=Float,Description="Genotype Likelihood, log10-scaled likelihoods of the data given the called genotype for each possible genotype generated from the reference and alternate alleles given the sample ploidy">
##INFO=<ID=TYPE,Number=A,Type=String,Description="The type of allele, either snp, mnp, ins, del, or complex.">
##INFO=<ID=LEN,Number=A,Type=Integer,Description="allele length">
##INFO=<ID=ORIGIN,Number=1,Type=String,Description="Decomposed from a complex record using vcflib vcfallelicprimitives and alignment with obsolete SW.">
#CHROM  POS     ID      REF     ALT     QUAL    FILTER  INFO    FORMAT  vc_freebayes_in
chr22   11066446        .       G       A       5700.41 .       .       GT:GQ:DP:AD:RO:QR:AO:QA:GL      0/1:160.002:436:198,238:198:7122:238:8563:-588.912,0,-509.596