Hello,
I have exome sequencing data for a few sets of trios in which the offspring have phenotypically related but probably genetically distinct diseases. The parents are unaffected so I am particularly interested in identifying de novo mutations in the offspring.
My plan at present is to analyse each sample separately up to the variant calling phase then call variants jointly in each trio. I was going input all three (mother, father, child) analysis-ready BAM files to the GATK UnifiedGenotyper to obtain one vcf per trio and then use GATK's PhaseByTransmission and ReadBackedPhasing tools to perform phasing and finally filter.
I know you can pass a ped file to the UnifiedGenotyper but does anyone know if it uses pedigree information to infer the correct genotypes? If not, can anyone suggest a good tool (preferably one that takes in and outputs a vcf) for joint calling in trios? I have heard of a few: FamSeq, PolyMutt and DeNovoGear, but I'm not sure of their relative merits.
Finally, is it better to call variants with the UnifiedGenotyper on all the trios combined, or each trio separately?
Best wishes!
I have exome sequencing data for a few sets of trios in which the offspring have phenotypically related but probably genetically distinct diseases. The parents are unaffected so I am particularly interested in identifying de novo mutations in the offspring.
My plan at present is to analyse each sample separately up to the variant calling phase then call variants jointly in each trio. I was going input all three (mother, father, child) analysis-ready BAM files to the GATK UnifiedGenotyper to obtain one vcf per trio and then use GATK's PhaseByTransmission and ReadBackedPhasing tools to perform phasing and finally filter.
I know you can pass a ped file to the UnifiedGenotyper but does anyone know if it uses pedigree information to infer the correct genotypes? If not, can anyone suggest a good tool (preferably one that takes in and outputs a vcf) for joint calling in trios? I have heard of a few: FamSeq, PolyMutt and DeNovoGear, but I'm not sure of their relative merits.
Finally, is it better to call variants with the UnifiedGenotyper on all the trios combined, or each trio separately?
Best wishes!
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