Calling somatic muttaions in pediatric tumor samples without matched normal samples

Question

[aditi.bagchi]

Hi , I am new to the world of bioinformatics. I currently have sequencing data (WES) of about 45 pediatric brain tumor samples (archived FFPE), I am keen on identifying mutational burden and mutational signatures in these samples. I don't necessarily want to discover a novel mutation and describe it's biological relevance. More use the pattern of mutational signatures to identify the causes of recurrence in tumors. The problem is like with most archived FFPE samples I don't have matched normal tissue. I am looking at the best approach to call somatic variants in these samples. Is Using gnomAD for filtering my best option? Is that a good resource for pediatric tumors? If no then what could be other potential sources for this.

Thank you for your advise. Aditi

Answer 1

[markus.riester]

Do you have a few normal samples sequenced using the same capture kit? Ideally sequenced in the same lab, but not necessarily.

If yes, then our PureCN tool might be worth a look. There is a downstream script (Dx.R) that calculates TMB and somatic signatures for tumor-only samples. But not sure how relevant somatic signatures are in very quiet pediatric WES samples and whether it's possible at all. You'll need > 50 mutations per sample