The effect direction of genes in the Hallmark Cancer Pathways

[Roni Haas]

Hello everyone,

I am using the hallmark cancer gene sets, downloaded from here:

http://www.gsea-msigdb.org/gsea/msigdb/download_file.jsp?filePath=/msigdb/release/7.5.1/h.all.v7.5.1.symbols.gmt

I was wondering if there is a way to know the effect direction of each gene, per each pathway (i.e. does the gene activate or inhibit that pathway).

I would greatly appreciate your help with that.

Thank you!

Roni

[Anthony Castanza]

HI Roni,

 

The Hallmarks collection was focused around building sets of coordinately regulated genes that can serve as a fingerprint for a given processes activity. The genes in the set aren't specifically activators or inhibitors, but rather indicators.

 

You can find the publication that describes the Hallmarks creation process here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707969/

 

-Anthony

 

Anthony S. Castanza, PhD

Curator, Molecular Signatures Database

Mesirov Lab, Department of Medicine

University of California, San Diego

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[Roni Haas]

Hi Anthony,

Thank you so much for the help!

I went over the method steps and would greatly appreciate your help with a follow-up question.

In "Step 5: Refining raw hallmark sets" there was the usage of gene expression data for refining the list of gene sets.

If I understand correctly, the degree of association between the expression of each gene in a pathway and the corresponding phenotype of that pathway using an appropriate dataset was tested to choose affecting genes. It is written that: "In the refinement procedure we focused on up-regulated genes"

Does it mean that the genes included in the hallmark pathway gene-sets are found to be upregulated when a high activity of that pathway was observed?

For example, if I take genes participating in the DNA repair pathway, and they are all up-regulated in my cells, that indicates a high activity of that pathway?

Thank you very much!

Roni

[Anthony Castanza]

HI Roni,

 

Yes, that is generally the case. The initial annotated clustering was refined using independent expression datasets to select out the response component that indicated activation of the pathway.

Therefore enrichment analysis that indicates positive enrichment of that set would likewise indicate putative activation of that pathway.

To view this discussion on the web visit https://groups.google.com/d/msgid/gsea-help/3c9b476d-e2d0-4299-8394-9d1c5d80f63dn%40googlegroups.com.

[Roni Haas]

Thank you very much for confirming!

Best,

Roni