Question: TMB Tumor Mutation Burden
1
gravatar for abibioinformatics
2.0 years ago by
abibioinformatics10 wrote:

HI,

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

Thanks,

Abilesh

cancer burden mutation tumor exome • 5.8k views
ADD COMMENTlink modified 10 months ago by Shicheng Guo8.0k • written 2.0 years ago by abibioinformatics10
4
gravatar for roy.granit
2.0 years ago by
roy.granit810
Israel/LabWorm
roy.granit810 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 2.0 years ago by roy.granit810
2

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

ADD REPLYlink written 24 months ago by markus.riester480
1

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

ADD REPLYlink written 24 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 21 months ago by ivivek_ngs4.9k
2
gravatar for Nicolas Rosewick
2.0 years ago by
Belgium, Brussels
Nicolas Rosewick8.6k wrote:

You can start by this paper : https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-017-0424-2

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 2.0 years ago by Nicolas Rosewick8.6k
3

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 2.0 years ago by dariober11k
1

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 21 months ago • written 21 months ago by Jeremy Leipzig19k
0
gravatar for Shicheng Guo
10 months ago by
Shicheng Guo8.0k
Shicheng Guo8.0k 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 10 months ago by Shicheng Guo8.0k
Please log in to add an answer.

Help
Access

Use of this site constitutes acceptance of our User Agreement and Privacy Policy.
Powered by Biostar version 2.3.0
Traffic: 1695 users visited in the last hour