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Infuence of Coverage Depth Difference in Tumor & Normal Sequencing Data in Somatic Mutation Calling
Hi, GATK team.
I'm planing to use Mutect & Mutect2 to call somatic mutations in Tumor and mathched Normal samples. I have a question about the coverage depth difference of Tumor and Normal samples. Since our team want to sequencing Tumor sample in 200X ~ 400X WES, when Normal sample in about 30X ~ 50X WGS. Tumor samples are about 5 times to 10 times deeper than Normal samples. Is that okay for the Statistical Model in Mutect/Mutect2?
I have tested 150X tumor with 120X normal, and the same sample 150X tumor with 26X normal, only ~75% sites in concordence. In addition, more low variant-allele-frequence sites are detected in the 150X tumor with 26X normal samples. This is out of our expectation (we thought low coverage depth of normal may miss part of the low variant-allele-frequence sites).
Hopefully, your team could explain about this (in the Statistical Modelling), and give us some advise in sequencing depth design.
Thank you. Looking forward to your reply.