Picking up differences in mutation sets

Question

[James]

Hey all,

As a non-biology guy working on a bioinformatics project, I wanted to ask the following. Suppose I have two groups of human tumor samples given in mutation annotation format (MAF) ---- that is, two files, each MAF, for subgroup A and subgroup B.

What is the best way to discover (statistically and biologically) meaningful differences between these two groups, and how do I best visualize them?

I've seen Gene Ontology (GO) enrichment done on some data sets. Gene set enrichment analysis seems to be only for expression.

Thanks!

Answer 1

[Hamid Ghaedi]

You may use mafCompare function from the maftools R package to compare two maf files. Using this would provide you with differentially mutated genes by performing a Fisher exact test.

To visualize differences, I would suggest coBarplot from the same package which draws two barplots side by side for cohort comparison.

I am not sure if agree with your statement

"Gene set enrichment analysis seems to be only for expression."

Actually, you may do an over-representation analysis (ORA, kind of enrichment analysis) based on differentially mutated genes (identified through the above-mentioned steps) and see if differentially mutated genes are enriched in some pathways/GO terms.

[James]

Thank you for the reply! Two follow ups:

1) is there a way to use the MAF tools comparison to say 4 or 5 cohorts? 2) can you point me towards a good tutorial on ORA?