In this reply, it is stated that Correlation Adjusted MEan RAnk gene set testing (CAMERA) is not intended for use with Gene Ontology (GO) gene sets due to their "redundancy and lack of directionality", though I could not find any other explicit mention of this. I imagine it is something to do with the inner workings of CAMERA, though the exact reason is unfortunately lost on me.
After restricting the GO sets to only those genes quantified in the experimental data and applying reasonable set size filters [10, G - 1], suppose the redundancy could be mostly addressed by using a hierarchical clustering approach similar to what is described in the MSigDB v7.0 Release Notes (sections 3.2 and 3.7). In that case, would the lack of directionality of the GO still be enough of a problem to warrant a different competitive test? Would
limma::geneSetTest be more appropriate, despite not accounting for inter-gene correlation?
Note: I am aware that, in the RNA-Seq Analysis is Easy as 1, 2, 3 vignette and the Gene-expression data integration to squamous cell lung cancer subtypes reveals drug sensitivity publication, CAMERA is used in conjunction with sets from the C2 collection of the Molecular Signatures Database (MSigDB), where a number of terms (though perhaps not all) indicate directionality with "_UP" or "_DN" suffixes.