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Identifying Rare SNPs

bbimberbbimber HomeMember


I have been reading through GATK's docs and forums trying to wrap my head around the best way to approach the problem of sequencing viral populations. In this case, you have sequenced a sample comprised of an unknown number of genetic variants, and want to accurately identify point mutants. For example, a mutation present in a very low percent of the genomes sampled (ie. reads) could be real. If you sequence a diploid organism, you have only 2 possibilities at each position. We have no idea how many possibilities exist at each position of the viral genome. I have found this to be a difficult problem for most SNP callers, or at least I have not found the right sort of configuration to produce descent results. I have been trying to find parallels in other areas, and have been trying to find right keywords to use in searches, but have not had a lot of luck.

It occurred to me that there may be a parallel for some cancer studies. If you take a patient sample, some cells may be normal and some cells may carry the somatic mutation. It is a heterogeneous population, just like a viral swarm. The degree of heterogeneity will obviously depend on the nature of that sample. This may be a shot in the dark.

Does anyone have experience with this sort of problem, or do you have suggestions on areas or keywords where I should be looking? Note: I did find VPhaser2, which does look interesting.

Thanks in advance for any help or pointers.


  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie admin

    Hmm, this is not something we have any direct experience with. The idea of using cancer tools to do this is intriguing though. Have you looked into MuTect at all? It's built on the same framework as GATK, but is geared specially at calling variants in cancer. The major problem I can see for your application is that cancer tools typically depend on having a pair of samples (tumor & normal) to compare. This enables you to subtract the background of base variants found in the normal from the tumor variant calls. But obviously this design wouldn't be applicable for your viral analysis.

  • ClaraTClaraT ArgentinaMember

    Hello, I am facing this same problem, have you been able to solve it?

    Issue · Github
    by Sheila

    Issue Number
    Last Updated
    Closed By
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