An R package for Survival-based Gene Set Enrichment Analysis

Abstract

Functional enrichment analysis is usually used to assess the effects of experimental differences. However, researchers sometimes want to understand the relationship between transcriptomic variation and health outcomes like survival. Therefore, we suggest the use of Survival-based Gene Set Enrichment Analysis (SGSEA) to help determine biological functions associated with a disease’s survival. We developed an R package and corresponding Shiny App called SGSEA for this analysis and presented a study of kidney renal clear cell carcinoma (KIRC) to demonstrate the approach. In Gene Set Enrichment Analysis (GSEA), the log-fold change in expression between treatments is used to rank genes, to determine if a biological function has a non-random distribution of altered gene expression. SGSEA is a variation of GSEA using the hazard ratio instead of a log fold change. Our study shows that pathways enriched with genes whose increased transcription is associated with mortality (NES > 0, adjusted p-value < 0.15) have previously been linked to KIRC survival, helping to demonstrate the value of this approach. This approach allows researchers to quickly identify disease variant pathways for further research and provides supplementary information to standard GSEA, all within a single R package or through using the convenient app.