Identification Of Genes (Computationally) Driving Pathways

Question

[Dataminer]

Hi!

I have a RNA-seq data from three different samples and when I compare the expression of genes in a certain pathway (for example say Cell cycle) I see that majority of genes in sample1 are upregulated compared to expression of genes in sample 2 and 3. The expression of majority of genes in sample 3 is repressed (comparatively), while sample 2 shows mixed trends compared to sample 1 and 2.

I am interested in identifying the genes that are master regulators of a pathway that will enable me to draw conclusion or atleast give indication if these pathways are down or upregulated.

Is their a way to find master regulators of pathways or a list of master regulators is available some where or has it been already published which can be used?

Any suggestions?

Thank you

Answer 1

[munch]

Maybe CluePedia can help you here. Here is an example: http://www.ici.upmc.fr/cluepedia/CluePedia_Fig1_Example.pdf

From the website:

CluePedia provides a holistic view on a pathway or process by investigating experimental and in silico data from different perspectives: gene interrelations revealed by correlation weights, miRNAs regulatory aspects, protein - protein interactions as well as the functional context, in conjunction with ClueGO. This review is helpful for defining new hypothesis and strategies that allow one more step in understanding complex processes. The CluePedia ClueGO/Cytoscape plug-in is user friendly and has an expressive and intuitive visualization.

Answer 2

[brentp]

You could look into "key driver analysis" or KDA for microarrays. This paper has a nice description and use: http://www.biomedcentral.com/1752-0509/5/121

from the paper:

One primary goal of gene network analysis is to identify key regulatory components, or key drivers, of sub-networks with respect to varying biological contexts [25,27]. The KDA takes as input a set of genes (G) and a gene causal (directed) network N. The objective is to identify the key regulators for the gene sets with respect to the given network.

There are modules to do KDA in cytoscape.