GO enrichment analysis from peaks to corresponding genes for each MSigDB Oncogenic Signatures or GO IDs using rGREAT

Question

[Researcher]

Hi All, I used rGREAT to do GO enrichment analysis for the peak calls from macs2, where I got enriched GO IDs and MSigDB Oncogenic Signatures. Can anyone help me to automate this process in such a way that I will get a table with all enriched GO IDs or MSigDB Oncogenic Signatures with corresponding significant genes? Thank you

[jared.andrews07]

What have you tried? What final output do you want? We need hard examples of what you have, what you've tried, and what you expect to get out at the end. We can't help you much otherwise.

[Researcher]

Hi @jared.andrews07

I have a list of annotated chip-seq peaks and their corresponding genes. In order to check if there is any enrichment for the genes that are from any specific oncogenic or any immunological pathway, I have used rGREAT. rGREAT with its getEnrichmentTables() provided me a file with list of enriched pathways and their significance level. But it doesn't tell which genes were used and overlapped with a pathway of my interest.

Can you suggest any smart approach to do the same?

I hope it is clear and make sense now.

Answer 1

[jared.andrews07]

That is much more clear, thank you.

And you're right, apparently there isn't a great approach to getting the genes in each enriched pathway. The only way that I can see to do it is by looking at each pathway you're interested in individually. A bit of a hassle, but you could write a function to do it for each pathway of interest easily enough. Something like this:

res = plotRegionGeneAssociationGraphs(job, ontology = "GO Molecular Function",
    termID = "GO:0004984")

res[1:2, ]

Yields:

## GRanges object with 2 ranges and 2 metadata columns:
##       seqnames              ranges strand |        gene   distTSS
##          <Rle>           <IRanges>  <Rle> | <character> <numeric>
##   [1]     chr1 247871555-248931674      * |       OR2M4      -616
##   [2]     chr3   96368632-99050767      * |      OR5AC2    -96317
##   -------
##   seqinfo: 7 sequences from an unspecified genome; no seqlengths

[Researcher]

Hi @jared.andrews07

Thank you for your kind help, this is really helpful. I am just curious to ask about "GO" termID as you specified in the above example. How can I get the similar for any other pathway of my interest like for example "Sonic Hedgehog (Shh) Pathway".

[jared.andrews07]

You need to change the ontology to whatever ontology that term/pathway would be found in and then change the termID to whatever the ID for the pathway is.