Difference in the output when I upload .gmt file

[Pushti Mehta]

Hi, 

I would like to tell you that when I use the command gs_res = gp.enrichr(gene_list=data.gene,  gene_sets='MSigDB_Hallmark_2020', organism='human', outdir=None), I get 5 significant gene set. However, when I input the .gmt file of the same gene set library from MSigDB (https://data.broadinstitute.org/gsea-msigdb/msigdb/release/7.2/h.all.v7.2.symbols.gmt) I get only 2 significant pathways. Can you please explain the reason behind this. 

I have checked the contents of both the gene sets. It is exactly the same except for the order of the genes in the gene set. I seems like it affects the scoring. Can you please explain why and how? 

Please let me know at the earliest. 

[Castanza, Anthony]

Hello,

We don’t support, or endorse the use of enrichR for performing set analysis. My recommendation would be to run a proper Gene Set Enrichment Analysis, using the GSEA Desktop software with the latest MSigDB gene sets and gene mapping tables (chip files). This should provide a much more robust analysis than the enrichR analysis, which also appears to be using quite old versions of MSigDB.

That said, one reason this could be occurring is that gene symbols are not really a stable namespace and some may have changed between the two versions there (“Hallmark_2020” is not a proper MSigDB version so it’s impossible to say which specifically that is), but if its different than the 7.2 release you used in the second analysis, then a different number of genes may have been identified in your dataset resulting in a slightly different scoring.

 

-Anthony

 

Anthony S. Castanza, PhD

Curator, Molecular Signatures  Database

Mesirov Lab, Department of Medicine

University of California, San Diego

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