7 Homework Assignment: GSEA

GSEA

Steps

1. Downloaded mesenchymal vs immuno rank file
2. Downloaded Human_GOBP_AllPathways_no_GO_iea_March_01_2021_symbol.gmt
3. Ran GSEAPreranked using ranked file and genesets
   • maximum geneset size of 200
   • minimum geneset size of 15
   • Set Collapse/Remap to gene symbols to No_Collapse (to use dataset as is)

Parameters setting

The maximum size is set to 200 to ensure that large, broad genesets that are not directly related to our pathways off interest are not included in the analysis. Large genesets are also very computationally heavy to analyse.

The minimum size is set to 15 to prevent small, over-specific genesets that may not capture the the full context of the phenotypes of interest from being included in the analysis.

Top gene sets for subtypes

Mesenchymal

Geneset: HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION%MSIGDB_C2%HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION

• P-value: 0.0
• ES: 0.8635254
• NES: 2.5300958
• FDR: 0.0
• Number of genes in leading edge = size $\times$ leading edge tags percentage = 145 $\times$ 0.57 $\approx$ 83
• Top gene associated with geneset: FBN1

Immunoreactive

Geneset: HALLMARK_INTERFERON_ALPHA_RESPONSE%MSIGDB_C2%HALLMARK_INTERFERON_ALPHA_RESPONSE

• P-value: 0.0
• ES: -0.85694104
• NES: -2.8794117
• FDR: 0.0
• Number of genes in leading edge = size $\times$ leading edge tags percentage = 79 $\times$ 0.73 $\approx$ 58
• Top gene associated with geneset: PROCR

References

• Merico D, Isserlin R, Stueker O, Emili A, Bader GD. Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS One. 2010;5(11):e13984. Published 2010 Nov 15. doi:10.1371/journal.pone.0013984
• Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545-15550. doi:10.1073/pnas.0506580102