leapR | R Documentation |
leapR is a wrapper function that consolidates multiple enrichment methods.
leapR(geneset, enrichment_method, ...)
geneset |
is a list of four vectors, gene names, gene descriptions, gene sizes and a matrix of genes. It represents .gmt format pathway files. |
enrichment_method |
is a character string specifying the method of enrichment to be performed, one of: "enrichment_comparison", "enrichment_in_order", "enrichment_in_sets", "enrichment_in_pathway", "correlation_enrichment". |
... |
further arguments |
Further arguments and enrichment method optional argument information:
eset | Is an ExpressionSet of expression data, with features as rows and n sample/conditions as columns.
The Annotation field ideally describes the data type (i.e. proteomics, phosphoproteomics), the featureData field describes any mapping
identifiers and the phenoData field describes any phenotyptic data. We recommend that the `Annotation` slot contain the omics data type for when using with `combine_omics`
This is an required for all active enrichment methods with the exception of 'enrichment_in_relationships'. |
id_column | Is a character string, present in the featureData slot, that is used to specify a column for identifiers to map to enrichment libraries.
If missing, the rownames of the ExpressionSet will be used.
|
primary_columns | Is a character vector composed of column names from eset (either in the `exprs` or in the `featureData`),
that specifies a set of primary columns to calculate enrichment on.
The meaning of this varies according to the enrichment method used - see the descriptions for each method below.
This is an optional argument used with 'enrichment_in_order', 'enrichment_in_sets', and 'enrichment_comparison' methods. |
secondary_columns | Is a character vector of column names for comparison, pulled from the `exprs` of the ExpressionSet. This is an optional argument used with 'enrichment_comparison' methods. |
threshold | Is a numeric value, an optional argument used with 'enrichment_in sets' method which filters out abundance values or p-values (depending on what `primary_columns` is used) either above or below it. |
greaterthan | Is a logical value that defaults to TRUE, it's used with 'enrichment_in_sets' method.
When set to TRUE, genes with `primary_columns` value above the threshold argument are kept.
When set to FALSE genes with `primary_columns` value below the threshold argument are kept.
This is an optional argument used with 'enrichment_in_sets' method. |
minsize | Is a numeric value, an optional argument used with 'enrichment_in_sets' and 'enrichment_in_order". |
idmap | Is...??. This is an optional argument used with 'enrichment_in_relationships' method. |
fdr | A numerical value which specifies how many times to randomly sample genes to calculate an empirical false discovery rate, is an optional argument used with 'enrichment_comparison' method. |
min_p_threshold | Is a numeric value, a lower p-value threshold and is an optional argument used with 'enrichment_comparison' method. |
sample_n | Is a way to subsample the number of components considered for each calculation randomly. This is an optional argument used with 'enrichment_comparison' method. |
Enrichment Methods:
enrichment_comparison
Compares the distribution of abundances between two sets of conditions for each pathway using a t test. For each pathway in geneset
uses a t test to compare the distribution of abundance values/numbers in eset
primary_columns
with those in
eset
secondary_columns
. Lower p-values for pathways indicate that the expression of the pathway is
significantly different between the set of conditions in primary_columns and the set of conditions in secondary_columns.
Optionally, users can specify fdr
which will calculate an empirical p-value by randomizing abdunances
fdr
number of times. If the min_p_threshold
is specified the method will only return pathways with an
adjusted p-value lower than the specified threshold. If sample_n
is specified the method will subsample the
pathway members to the specified number of components.
enrichment_in_order
Calculates enrichment of pathways based on a ranked list using the Kologmorov-Smirnov test.
For each pathway in geneset
uses a Kolgmorov-Smirnov test for rank order to test if the distribution
of ranked abundance values in the eset
primary_columns
is significant relative to a random
distribution. Note that currently primary_columns
only accepts a single column for this method.
enrichment_in_sets
Calculates enrichment in pathway membership in a list (e.g. highly differential proteins) relative to background using Fisher's exact test.
For each pathway in geneset
uses a Fisher's exact test over- or under- representation of a list
of components specified. If targets
are specified this must be a vector of identifiers to serve
as the target list for comparison. If eset
and primary_columns
are specified then threshold
specifies
a threshold value for determining the target list of components to test. Specifying greaterthan
to be False
will result in components with values lower than the specified threshold
. If eset
is
a data frame or matrix, the background used for calculation will be taken as the rownames of eset
enrichment_in_pathway
Compares the distribution of abundances in a pathway with the background distribution of abundances using a t test
For each pathway in geneset
calculates the signficance of the difference between the abundances
from pathway members versus abundance of non-pathway members in the set of conditions specified by primary_columns
.
Optionally, users can specify fdr
which will calculate an empirical p-value by randomizing abdunances
fdr
number of times. If the min_p_threshold
is specified the method will only return pathways with an
adjusted p-value lower than the specified threshold. If sample_n
is specified the method will subsample the
pathway members to the specified number of components.
correlation_enrichment
Calculates the enrichment of a pathway based on correlation between pathway members across conditions versus correlation between members not in the pathway.
For each pathway in geneset
calculates the pairwise correlation between all pathway members and non-pathway members
across the specified primary_columns
conditions in eset
. Note that for large matrices this can take a long
time. A p-value is calculated based on comparing the correlation within the members of a pathway with the correlation
values between members of the pathway and non-members of the pathway.
data frame with results
library(leapR)
# read in the example abundance data
# read in the example transcriptomic data
tdata <- download.file("https://figshare.com/ndownloader/files/55781153",method='libcurl',destfile='transData.rda')
load('transData.rda')
p <- file.remove("transData.rda")
# read in the pathways
data("ncipid")
# read in the patient groups
data("shortlist")
data("longlist")
# use enrichment_comparison to calculate enrichment in one set of conditions (shortlist) and another
# (longlist)
short_v_long = leapR(geneset=ncipid, enrichment_method='enrichment_comparison',
eset=tset, primary_columns=shortlist, secondary_columns=longlist)
# use enrichment_in_sets to calculate the most enriched pathways from the highest abundance proteins
# from one condition
onept_sets = leapR(geneset=ncipid, enrichment_method='enrichment_in_sets',
eset=tset, primary_columns="TCGA-13-1484", threshold=1.5)
# use enrichment_in_order to calculate the most enriched pathways from the same condition
# Note: that this uses the entire set of abundance values and their order - whereas
# the previous example uses a hard threshold to get a short list of most abundant proteins
# and calculates enrichment based on set overlap. The results are likely to be similar - but
# with some notable differences.
onept_order = leapR(geneset=ncipid, enrichment_method='enrichment_in_order',
eset=tset, primary_columns="TCGA-13-1484")
# use enrichment_in_pathway to calculate the most enriched pathways in a set of conditions
# based on abundance in the pathway members versus abundance in non-pathway members
short_pathways = leapR(geneset=ncipid, enrichment_method='enrichment_in_pathway',
eset=tset, primary_columns=shortlist)
# use correlation_enrichment to calculate the most enriched pathways in correlation across
# the shortlist conditions
short_correlation_pathways = leapR(geneset=ncipid, enrichment_method='correlation_enrichment',
eset=tset, primary_columns=shortlist)
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