I am trying to identify somatic mutations on healthy subjects (specifically in WES samples). As of now, I have found a couple of papers who have done similar studies such as this paper where somatic mutations in healthy subjects are identified (using RNA-SEQ data). But in my case, I want to find somatic mutations from normal WES samples. For somatic mutations, we need both tumors and matched normal samples to identify somatic mutations but how to identify somatic mutations from normal samples only. Please suggest. Thanks.

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    $\begingroup$ You can follow the GATK pipeline $\endgroup$
    – csgroen
    Sep 8 '20 at 12:21
  • $\begingroup$ @csgroen: As I have mentioned in my question, I have to find somatic mutations in normal samples only. The link you have shared contains the GATK pipeline for somatic mutations with tumor and matched normal samples. I am already aware of this. Thanks. $\endgroup$ Sep 8 '20 at 12:32
  • $\begingroup$ Hm, I see... The issue is that you need your 'baseline' germline genome to be able to call somatic mutations. Otherwise, how can you know if they are germline or somatic? $\endgroup$
    – csgroen
    Sep 8 '20 at 12:41
  • $\begingroup$ Yes. Precisely. Or I just found one way in this paper (Whole-genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type) in which conditions are not clear to me. $\endgroup$ Sep 8 '20 at 13:08
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    $\begingroup$ @PhoenixMu he wants somatic, not germline mutations. That's actually the challenge, as it is normal tissue and doesn't have a proper reference. But personally, I think what I described from my interpretation of the paper you shared seems to be at least on the correct path. Align against reference genome and remove common SNPs. It's not perfect, there will be false postiives and negatives, but it should work overall. $\endgroup$
    – csgroen
    Sep 9 '20 at 8:32

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