Activation of pathways

Question

[Ron]

Hi everyone,

I have taken data from TCGA and doing a comparison between high phospho AKT tumors and low phospho AKT tumors for enrichment of AKT pathways.Basically I want a set of genes which show a clear difference between these kind of tumors.

I have done differential expression of genes but they don't give a good enough result by taking top genes.The purpose is to get a set of genes which differentiate between these two types of tumors and show the enrichment of this specific pathway.Is there any cell line or microarray data that I could use?

Best,
Ron

Answer 1

[Sam]

The target genes might not be in the top gene list. One thing that you can try is to use SPIA together with the KEGG pathway database. If I remember correctly, the SPIA package does ship with an old version of KEGG which contains the AKT pathway information. You can then use the SPIA package to see if the AKT pathway is significantly differentiated

[Ron]

Is there any list of genes that I could get from any prior research. For example I came across this paper.

[Sam]

You want the pathway or the genes? If you are talking about the PI3K pathway, then it is here

[Ron]

I want a set of genes whose up regulation tells that, yes the PI3K pathway is activated. When PI3K pathway is activated then certain genes are unregulated.

[Sam]

That will require you to understand what the pathway is about. For example, using PI3K as example, do you know which gene represent the activation of PI3K? Is the expression of AKT alone representative of the activation of PI3K pathway? If so, you can read the KEGG graph and see what genes can lead to the up-regulation of AKT. However, pathway are usually dynampic and complex. It is difficult to actually tell whether if something is up-regulated together with the pathway without having any actual data. So that might be something to keep in mind

[Ron]

I don't know which genes represent the PI3K pathway activation and thats what I precisely want to know.I am not sure if a single gene AKT can tell us about the pathway being activated.

[Sam]

Maybe you want to look at this?

http://www.genome.jp/dbget-bin/www_bget?map04151