Regulated Genes In A Pathway

Question

[sirinda111]

I want to get a list of regulated genes per pathway. The regulated genes are the target genes of transcription factors of a pathway and the proteins of the regulated genes are the output of the pathway. I have been searching for a dew days and I can't find such a dataset. However, there are some databases such as PAZAR that provides a dump of the TFs and genes regulated by them. My questions are

• Let's say If a TF t1 and a gene g1, one of TF t1's target genes, are on the same pathway p1, can I infer that gene g1 is regulated by a pathway p1?
• If I can't infer such a statement. How can I use the TF-target gene pair to infer a pathway that the target gene is regulated? Since each TF can have more than 1 target gene and each target gene can also be regulated by more than 1 TFs

PS. Is there any database that provide a list of regulated genes per pathway? I still hope that such data exists. I am new to this research area and trying to put the pieces of information together. Any recommendations on tutorial/online resources (for non-biologists) that I can learn more about this stuff will be appreciated too :) Thanks!

[ewre]

haven't got ur idea. what do you mean by 'a target gene of a pathway p1' in your first statement?

[sirinda111]

I mean the gene g1 'is regulated by a pathway p1'

Answer 1

[Charles Warden]

Truly proving causality is difficult, but the typical solution to calculate functional enrichment: if more members of a pathway or targets of a transcription factor appear by chance in a gene list, then it is typically inferred that the pathway, transcription factor, etc. is important.

I think GATHER is a good open-source tool for this sort of analysis:

http://gather.genome.duke.edu/

If your institution has a license, I think IPA is the best option (which has canonical pathway as well as transcriptional regulator analysis functions).

[sirinda111]

IPA sounds interesting. I will check it out. Actually, I want to get a list of genes in a pathway (especially signalling pathways) that control cell's function or cell growth, cell death, cell differentiation.

Ultimately, my main goal is that, given a pathway and expression levels of all genes in a pathway, I want to tell if the pathway (of a test cell) is working normally. And I think one way to check that is to compare the expression levels of those genes (which are targets of transcriptional factors?) in the pathway of the test cell with expression levels of those genes in the pathway of other normal cells.

[Charles Warden]

Ok - I think you are already on the right track. In the open-source world, you can check GO and KEGG for those sorts of genes. After that you can just keep an eye out for those groups / pathways in your enrichment analysis.

[sirinda111]

I see. Thank you so much!