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Several gene set enrichment methods are available, the most famous/popular is the Broad Institute tool. Many other tools are available (See for example the biocView of GSE which list 82 different packages). There are several parameters in consideration :

  • the statistic used to order the genes,
  • if it competitive or self-contained,
  • if it is supervised or not,
  • and how is the enrichment score calculated.

I am using the fgsea - Fast Gene Set Enrichment Analysis package to calculate the enrichment scores and someone told me that the numbers are different from the ones on the Broad Institute despite all the other parameters being equivalent.

Are these two methods (fgsea and Broad Institute GSEA) equivalent to calculate the enrichment score?

I looked to the algorithms of both papers, and they seem fairly similar, but I don't know if in real datasets they are equivalent or not.

Is there any article reviewing and comparing how does the enrichment score method affect to the result?

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2 Answers 2

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According to the FGSEA preprint:

We ran reference GSEA with default parameters. The permutation number was set to 1000, which means that for each input gene set 1000 independent samples were generated. The run took 100 seconds and resulted in 79 gene sets with GSEA-adjusted FDR q-value of less than 10−2. All significant gene sets were in a positive mode. First, to get a similar nominal p-values accuracy we ran FGSEA algorithm on 1000 permutations. This took 2 seconds, but resulted in no significant hits due after multiple testing correction (with FRD ≤ 1%).

Thus, FGSEA and GSEA are not identical.

And again in the conclusion:

Consequently, gene sets can be ranked more precisely in the results and, which is even more important, standard multiple testing correction methods can be applied instead of approximate ones as in [GSEA].

The author argues that FGSEA is more accurate, so it can't be equivalent.

If you are interested specifically in the enrichment score, that was addressed by the author in the preprint comments:

Values of enrichment scores and normalized enrichment scores are the same for both broad version and fgsea.

So that part seems to be the same.

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  • $\begingroup$ Yes, the preprint talk much about how the p-values are differently calculated, but I was asking about if the enrichment scores is the same or not, I was aware of the different ways of calculating the p-values. I find the answer by the author himself $\endgroup$
    – llrs
    Commented May 21, 2017 at 10:39
  • $\begingroup$ Sorry. I didn't realize that you were asking specifically about the enrichment score. You may want to edit the question to make that more obvious. $\endgroup$
    – burger
    Commented May 21, 2017 at 19:49
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I found that the author responded that in the discussion in the preprint,

I wonder is the enrichment score calculated the same way as in broad gsea?

Values of enrichment scores and normalized enrichment scores are the same for both broad version and fgsea.

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