Enrichment score of ssGSEA

Question

[priyanka08993]

Can ssGSEA enrichment scores be negative ? What are range of values for ssGSEA enrichment score ?

Answer 1

[psm]

I'm not sure about the range but I have definitely obtained negative scores. I suppose it depends on the distribution of expression values for genes in the geneset vs distribution of expression values for all genes of that sample (my interpretation of the methods in their original paper)

"The gene expression values for a given sample were rank-normalized, and an enrichment score was produced using the Empirical Cumulative Distribution Functions (ECDF) of the genes in the signature and the remaining genes. This procedure is similar to GSEA but the list is ranked by absolute expression (in one sample).The enrichment score is obtained by an integration of the difference between the ECDFs. For a given signature G of size NG and single sample S, of the dataset of N genes, the genes are replaced by their ranks according the their absolute expression L={r1, r2, …, rN}. The list is then ordered from the highest rank N to the lowest 1. An enrichment score ES(G, S) is obtained by a sum (integration) of the difference between a weighted ECDF of the genes in the signature PwG and the ECDF of the remaining genes PNG"

[from Systematic RNA Interference Reveals That Oncogenic KRAS-driven Cancers Require TBK1, Nature 2009, Barbie et al] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783335/

[stefano.percio]

I have the same doubt. Does negative ssGSEA score mean that the gene set is enriched among the lowest rank genes on that sample? Reading the paper, negative scores should mean that there is an enrichment in the remaining genes instead of the genes of a specific gene set.

[psm]

I've since switched to GSVA - another way to perform single sample enrichments. It's very easy to test and use in R, and the numbers make sense. I'm not sure whether ssGSEA is still being maintained.