The panel size of WGS to use for calculating TMB
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21 months ago
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Hello everyone.

Usually, in some research, the TMB (tumor mutation burden) is calculated as:

( TMB = non-synonymous mutations count / panel size in Mb )

How abount WGS? As you known, non-synonymous mutations are mostly in exons. Should we set the panel size to 3.0 GB? Or use the size of exomes?

sequencing next-gen genome TMB WGS • 841 views
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I would take genes only. Honestly, I am not very good in this topic, but non-synonymous mutation outside of protein-coding region seems something "undefined" for me.

UPD: here they use all the mutations: https://cancerres.aacrjournals.org/content/canres/early/2018/09/14/0008-5472.CAN-18-0254.full.pdf - but I guess TMB calculated in this way will differ from the one you obtain from panels

UPD2: well, it actually depends on what you try to show - how many mutations tumor acquire or how well the patient will react to immunotherapy (for many cancers TMB is used as a predictor of ICB response, not for all of them, since high TMB is believed to lead to neoepitopes which may be recoginsed by immune system)

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Thanks for your sharing, Demidov. In our research, we will compare the TMB of samples, sequenced by WGS, with TMBs from TCGA's work. Thus, maybe setting the panel size to exome will be reasonable?

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Yeap, i would do so, even may be using the same panel as they did, however, may be their data is more deep since it is WES...

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