Question: TMB Tumor Mutation Burden
gravatar for abibioinformatics
17 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 • 4.8k views
ADD COMMENTlink modified 12 weeks ago by Shicheng Guo7.6k • written 17 months ago by abibioinformatics10
gravatar for roy.granit
17 months ago by
roy.granit800 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 17 months ago by roy.granit800

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

ADD REPLYlink written 17 months ago by markus.riester470

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

ADD REPLYlink written 16 months ago by poisonAlien2.8k

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 13 months ago by ivivek_ngs4.8k
gravatar for Nicolas Rosewick
17 months ago by
Belgium, Brussels
Nicolas Rosewick7.8k 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 17 months ago by Nicolas Rosewick7.8k

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 17 months ago by dariober10k

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 13 months ago • written 13 months ago by Jeremy Leipzig18k
gravatar for Shicheng Guo
12 weeks ago by
Shicheng Guo7.6k
Shicheng Guo7.6k wrote:

The TMB is defined as the total number of nonsynonymous mutations per coding area of a tumor genome. Initially, it was determined using whole exome sequencing, but due to the high costs and long turnaround time of this method, targeted panel sequencing is currently being explored to measure TMB.

samtools flagstat can be used for total base calculation.

ADD COMMENTlink written 12 weeks ago by Shicheng Guo7.6k
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