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filtering VCF files

Dear all,

after reading the submission for SMC (Somatic Mutation Challenge), we have identified a submission does the filtering of the VCF files in the following way (please see below) : any suggestions regarding a package that implements this filtering strategies ? thanks !

  • Read depth filtering: remove mutations when at least 2/3 of mutant allele bases in the tumor sample are of base quality < 25
  • Mapping quality filter: remove mutations when the median mapping quality of reads supporting mutant allele is < 20
  • Read position filter: remove mutations when the mutant allele is localized only at the extremities of reads (+/- 8 bases)
  • Strand bias filter: remove mutations when fisher test indicates strand disequilibrium only for the mutant allele (threshold 0.001)
  • Match normal filter: remove mutations when the mutant allele is present in more than 3% of the reads at a quality > 25 in the matching normal sample
  • Simple repeats filter: remove mutations that fall into a repeated region of the genome
  • Centromer filter: remove mutations that fall into centromer or telomer regions of the genome
  • Panel of normal filter: remove mutations that appear to be a SNP (3% of mutant allele) in at least 2 of other normal genomes, or that are frequent sequencing error (> 1 read carrying mutant allele) in at least half of the genomes in the pane
vcf

Thank you gentlemen !

1 answer

for almost all those tools I would use samtools view (SNP-POS) piped into https://github.com/lindenb/jvarkit/wiki/BioAlcidae to parse the reads and their cigar string in order to create a BED file. The VCF would be then filtered-out with this bed and betools.

thanks Pierre ! please consider validated the previous questions ! About BioAlcidae ..looks a bit too complicated, although a specific example would help certainly ! Is there perhaps an alternative way to BioAlcidae ? thanks !

I don't say it's easy :-) but as far as I can see , most all the filters you need requires programming a new tool.

yes, quite complicated, especially when various somatic callers do not provide all the needed fields in the VCF files ;)

thanks Pierre, that was a great effort, thanks for sharing its results !

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