R: Perform gene set enrichment analysis on a miRNApath object
runEnrichment
R Documentation
Perform gene set enrichment analysis on a miRNApath
object
Description
This method performs a hypergeometric enrichment analysis on
a miRNApath object, which should already contain miRNA data,
miRNA-gene associations, gene-pathway associations, and some
criteria for filtering miRNA hits from the full tested set.
An object of type mirnapath containing data resulting from
the loadmirnapath method.
Composite
Defines whether the enrichment treats miRNA-gene as the
enriched entity, or uses only the gene.
groups
List of groups to include in the analysis, although each
group is analyzed independent from the other groups.
permutations
The number of permutations to use in calculating an adusted
P-value. Value of 0 will perform no permutations.
Details
The composite flag indicates whether to treat the fully
expanded miRNA-gene combinations as separate enrichment events
(TRUE), or whether to treat all effects on one gene as one
collective event. The latter case reverts to the classic
un-ordered hypergeometric enrichment technique.
However the expansion of combinations is the current method
chosen to represent the multiple predicted effects of miRNAs
to one gene, and the predicted effect of one miRNA to multiple
genes. The algorithm will identify statistically significantly
enriched results when the combination of these effects is
greater than would be anticipated by random chance.
The adjusted P-value is calculated using the rank of
unadjusted P-values divided by the number of permutations
minus one (such that the best rank from 1,000 permutations
yields an adjusted P-value of 0.001.) The default value 0 was
put in place to save time, since most adjustments resulted in
stronger "hits" and weaker "non-hits" in terms of pathways
enriched. Thus the results are not substantially changed, and
permutation adjustment is saved for the final result set.
Value
The method returns an object of type mirnapath, a list with
components:
mirnaTable
data.frame containing the miRNA results data
columns
list containing the names of required column headers
associated to the actual column header supplied in the
dataset contained in mirnaTable. Required headers:
mirnacol, assayidcol, groupcol, filterflagcol.
groupcount
The number of groups contained in mirnaTable using the
groupcol, if supplied
state
The current state of the object, in this case "enriched".
mirnaGene
data.frame containing associations between miRNAs and
genes.
mirnaPathways
data.frame containing gene-pathway associations.
pathwaycount
Numerical value indicating how many pathways are
available in the data, provided for convenience.
filters
List of filters applied to the data, which may include:
"P-value", "Fold change", and/or "Expression".
enrichment
Enrichment summary data in the form of a list of elements
for each sample group (the sample group is the name of
each element.) Each list element is itself a list with
enrichment result data for each sample group, as
independently calculated: "pvalues" - list of P-values
named by pathway ID. "Measured pathway mirnaGenes" -
total number of miRNA-gene-pathway combinations measured,
which gives some idea of the overall coverage of pathways.
The general point is that miRNAs have the potential to
cover many genes and pathways. "Total mirnaGenes" - number
of miRNA-gene combinations represented in the data.
"Enriched pathway mirnaGenes" - number of miRNA-gene values
enriched in the pathway tested. "Enriched by miRNA" - list
of miRNAs involved in the pathway tested, with the list of
genes in parentheses per miRNA. "Enriched by Gene" - same
as previous except switching gene and miRNA. "Total
enriched mirnaGenes" - the total number of miRNA-gene
values involved in any pathway enrichment (significant or
not.) The total values are useful when comparing across
sample groups, looking particularly for groups with few
changes or those with a uniquely high number of changes.
Lastly, with permutations > 0 "Permutation P-value" will
contain the rank-adjusted P-value as described in the
details section.
pathwayList
Named list of pathways contained in the
mirnaobj$mirnaPathways object, named by the pathway ID
values found in the pathwayidcol column. This list
facilitates converting the data in the enrichment element
to pathway names, since those values are named by the
pathway ID to conserve memory.
John Cogswell (2008) Identification of miRNA changes
in Alzheimer's disease brain and CSF yields putative
biomarkers and insights into disease pathways, Journal of
Alzheimer's Disease 14, 27-41.
## Not run:
## Start with miRNA data from this package
data(mirnaobj);
## Now run enrichment test
mirnaobj <- runEnrichment( mirnaobj=mirnaobj, Composite=TRUE,
groups=NULL, permutations=0 );
## End(Not run)