[Bioc-devel] A geneSet data class for facilitating GSEA
Mark W Kimpel
mwkimpel at gmail.com
Sun Mar 18 17:33:15 CET 2007
I'm going to jump in here on the GSEA direction of change issue as a
molecular biologist. I can think of examples where it would be relevant,
and important to test for, and examples where it would be totally
I am currently involved in research searching for genes involved with
preference for alcohol. We may want to use a geneSet that consists of
all the genes known to be directly involved in dopamine transmission in
the brain. Because these genes may be up or down regulated in some
unknown pattern because of feedback loops, direction of change would be
irrelevant. We just want to know if, on average, dopamine related genes
are differentially expressed. It may be that one receptor subunit is
up-regulated and another down-regulated, we wouldn't know any of this a
On the other hand, suppose we wanted to construct a geneSet with a set
of genes found significant in a mouse experiment and then see if this
geneSet was significant in a GSEA analysis of our rats. Although it may
not be, here the pattern of up/down may be important if pathways are
similarly different between preferring and non-preferring lines. In this
situation it would be nice to be able to test with both options, i.e.
with directionality taken into account and without it.
One way to do this would be for the geneSet object to contain a slot
(attribute) that indicates whether the geneSet has directional
information in it or not. Another slot would be a string describing how
the phenotypes used to construct the geneSet are related to the
directionality of individual genes (example: "Direction of change is
with respect to alcohol preferring vs. non-preferring, with +1
correlating with increased expression in the preferring phenotype and -1
to decreased expression.").
To make the use of this directionality optional, the GSEA algorithms
would look at the slot for directional information (TRUE/FALSE). If
FALSE, the a non-directional test would be applied, if TRUE, then a
function argument would have to state whether to use directional
information or not (TRUE/FALSE).
Certainly you developers would have a better handle than I on how to
implement this, but I thought I would jump in and give an idea of how an
end-user might use this information.
And sorry if I messed up the thread on this discussion, I get the digest
of the developer newsgroup.
Mark W. Kimpel MD
Department of Psychiatry
Indiana University School of Medicine
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