calculate mutation burden per gene

Question

[shubhrab]

Dear all,

I have a list of genes for which I want to calculate the mutations per MB.

How do I do this since every gene has a different gene size and the data is exome sequencing data.

Should I normalize it with respect to exome size or gene size. Also the coverage of the samples vary so that is a added variable.

Is there any existing utility that can do this?

--Thanks

Answer 1

[Brice Sarver]

This may not be the most helpful answer, but mutational burden can be calculated any of these ways. It's difficult to compare apples-to-apples among studies unless you say explicitly how you're doing it. You may be interested in the number of mutations per coding MB or per exon, which you'll be able to get from your annotation. If you have a large variability in coverage/depth among samples, you'll want to make sure that you take this into account so you don't bias the calculations due to false positives or false negatives.

This paper is a decent starting place outlining some of the different challenges and ways of estimating tumor mutational burden in a clinical setting.