Calculation of TMB on gene level

Question

[smrutimayipanda]

Hi all, I have TCGA cancer data and i want to calculate TMB on gene level. Can anyone please tell me how to do that? TCGA has TMB score based on patient level. I need on gene level. Thanks!

[svp]

TMB calculated by the number of non-synonymous somatic mutations per mega-base in coding regions. Performing TMB at gene level is technically incorrect.

[smrutimayipanda]

can you please tell me why it is technically incorrect?

[svp]

What is your understanding about Tumor mutational burden? If you know it clearly, then you will know what is technically incorrect.

TMB is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm

Generally, we calculate TMB as follows:

1. Compute the total number of bases that have minimum 10X coverage (Tcov_min), within the target regions. You can choose your X coverage

2. Count the number of deleterious somatic mutations called within the regions (Nmuts_mincov). With these compute the tumor mutation burden as: Nmuts_mincov/Tcov_min

   TMB = Nmuts_mincov / Tcov_min

[Zhenyu Zhang]

Is what you asked for just mutation frequency or mutation frequency adjusted by gene length?

[smrutimayipanda]

I am asking about TMB calculation on gene level, especially TCGA data

[svp]

different genes will have different length. The number of mutations that occur in genes with higher length are considerably more. Hence Zhenyu Zhang is asking whether you want to adjust it for gene length