Question: TMB Tumor Mutation Burden
gravatar for abibioinformatics
13 months ago by
abibioinformatics10 wrote:


Can someone help me with the formulae or a tool to identify the Tumor Mutation Burden from a Whole Exome Sequence?



cancer burden mutation tumor exome • 4.0k views
ADD COMMENTlink modified 10 months ago by sutturka120 • written 13 months ago by abibioinformatics10
gravatar for roy.granit
13 months ago by
roy.granit790 wrote:

Note that the human exome size is ~30Mb. So you can take the number of somatic mutations in a given tumor sample an divide that by 30 to obtain the Mut/Mb value (normally > 4-6 is considered 'hyper mutation')

Or maybe you can try this tool

ADD COMMENTlink written 13 months ago by roy.granit790

Instead of using 30 as denominator, I would use tools like GATK CallableLoci to get the exact number of bases.

ADD REPLYlink written 13 months ago by markus.riester320

I believe standard WXS capture sizes are around 50 mb. (eg; Agilent sure select)

ADD REPLYlink written 12 months ago by poisonAlien2.7k

I would go with either the GATK CallableLoci or the capture size , that should be the one in use rather than something arbitrary.

ADD REPLYlink written 10 months ago by ivivek_ngs4.7k
gravatar for Nicolas Rosewick
13 months ago by
Belgium, Brussels
Nicolas Rosewick7.4k wrote:

You can start by this paper :

In the method part :

TMB was defined as the number of somatic, coding, base substitution, and indel mutations per megabase of genome examined.

ADD COMMENTlink written 13 months ago by Nicolas Rosewick7.4k

I think the "number of mutations per magabase" could be a misleading estimate of TMB. The deeper you sequence the more mutations per magabase you find since you detect more and more variants with low allele frequency. Maybe one should weight a variant by its frequency in order to compute TMB. (NB, I just glanced through the paper.)

ADD REPLYlink written 13 months ago by dariober9.9k

I think they sequence to ridiculously high median depth (500X) so they might have started to saturate by then?

That having been said it's a crude metric for 2018 to say the least. I'm surprised it even has a name.

ADD REPLYlink modified 10 months ago • written 10 months ago by Jeremy Leipzig18k
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