Question: Variant calling for MNP
0
gravatar for nilus1432
5.3 years ago by
nilus143230
Singapore
nilus143230 wrote:

Hi All, 

I would like to know is there any program for variant calling for multiple-nucleotide polymorphisms. For eg. detecting cases like, Reference = 'ATA', Sample = 'GTC'.

thanks a lot

snp rna-seq • 3.0k views
ADD COMMENTlink modified 5.3 years ago by Len Trigg1.5k • written 5.3 years ago by nilus143230
4
gravatar for Len Trigg
5.3 years ago by
Len Trigg1.5k
New Zealand
Len Trigg1.5k wrote:

RTG Core calls haplotypes such as this. In reply to rbagnall, the benefit of calling as haplotypes rather than as individual SNPs is that the variant caller is able combine the evidence across both sites rather than calling them independently (e.g. read evidence containing all of ATA, ATC, GTA, GTC looks like het A->G and het A->C when looking at the sites separately, but is completely bogus from a haplotype perspective).

Whether the output is represented as multi-base calls or is decomposed into smaller variants is orthogonal and largely personal opinion. Either way, with complex calls you are likely to encounter cases where variants may have multiple alternative, equivalent representations. Even decomposition tools don't get you to a canonical form for all cases, so haplotype-based variant comparison tools such as rtg vcfeval are critical for accurate comparison of complex variants.

ADD COMMENTlink modified 12 months ago by _r_am31k • written 5.3 years ago by Len Trigg1.5k

Thanks Len, that makes sense.

ADD REPLYlink written 5.3 years ago by rbagnall1.7k
2
gravatar for Daniel Swan
5.3 years ago by
Daniel Swan13k
Aberdeen, UK
Daniel Swan13k wrote:

Freebayes calls MNPs and complex polymorphisms as well as SNPs and indels 

ADD COMMENTlink written 5.3 years ago by Daniel Swan13k

I'm curious,

What is the benefit of calling a multiple-nucleotide polymorphism as shown in @nilus1432 question, rather than calling an A>G and an A>C single nucleotide variant? The latter are easier to annotate (missense, frequency in population controls etc...).

 

ADD REPLYlink written 5.3 years ago by rbagnall1.7k
1

Because you can annotate them correctly. Calling two adjacent SNPs and passing them to something like VEP will give you two different SNP effects, but if it's a genuine dinucleotide change within say a codon, you need to be able to assess the effect of their presence as a unit.

ADD REPLYlink written 5.3 years ago by Daniel Swan13k
1

Thanks Daniel,

Yes that's true and something I hadn't considered. I will have to see if VEP annotates such MNPs; it looks like SNPEff does. Also, the train of thought led me to this paper which describes the issue a bit more for anyone interested, though I haven't tried the described software:

http://www.biomedcentral.com/1471-2164/16/569

ADD REPLYlink written 5.3 years ago by rbagnall1.7k
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