Proposed Analysis: is increased somatic mutational burden seen in ALT+ HGAT independent of ATRX status?

[jstundon]

What are the scientific goals of the analysis?

Determine whether increase in mutational burden seen is due to ATRX alone or ALT

What methods do you plan to use to accomplish the scientific goals?

Seprately analyze the mutational burden (again excluding hyper mutants) in ATRX mutant vs. WT and do an analysis to determine whether the difference seen in mutational burden is independent of ATRX

What input data are required for this analysis?

Same data as used for analysis of mutational burden previously

How long do you expect is needed to complete the analysis? Will it be a multi-step analysis?

Who will complete the analysis (please add a GitHub handle here if relevant)?

@runjin326

What relevant scientific literature relates to this analysis?

see pdf in email-- previous literature shows that loss of ATRX is associated with increased somatic mutational burden

[runjin326]

@jstundon - I have now added the figures in the PR https://github.com/d3b-center/Cole-telomere-analysis/pull/27. Also attaching here - let me know whether this answered your question and what other analyses I could do: TMB all mutations:

TMB missense mutations only:

Mut count all mutations:

Mut count missense mutations only:

[jstundon]

Thanks, this looks great!

Is there a way we can subtract out the effect of ATRX, perhaps similar to what was done with the survival analysis? I'm not sure if that's too convoluted.

Would you able to run the analysis of ATRX mutated vs. not ATRX mutated to see if there's a difference in TMB? I'm thinking/hoping that there's a difference in TMB between ATRX mutated & ATRX not mutated and that it's driven by the ALT status.

[jharenza]

so we should do 1 plot for TMB between ATRX WT/mut, 1 plot for TMB coding between ALT +/-, and one which combines them as in plot 1 above

[jharenza]

Think this has been done