Mergeomics (version 1.0.0)

kda.analyze.simulate: Weighted key driver analysis (wKDA) simulation

Description

Generates simulations for permutation test, which is performed to obtain the p-value for the enrichment score of a given hub for a specified module during the wKDA process.

Usage

kda.analyze.simulate(o, g, nmemb, nnodes, nsim)

Arguments

o

Observed enrichment score of a hub node assigned for a given module.

g

Sub-graph of a given hub and its neighbors (hubnet).

nmemb

Number of the members included in a given module.

nnodes

Number of the nodes in the whole graph (network) of the dataset.

nsim

Number of the iterations (simulations) performed for the permutation test.

Value

x

A list containing enrichment scores of the simulation's iterations

Details

kda.analyze.simulate performs permutation tests to obtain p-values for the enrichment score of a given hub node for a given module. It takes the observed enrichment score of the given hub, hubnet (subgraph of the hub and its neighbors), number of the members of the given module, total number of the nodes in the entire graph of the dataset, and number of the simulations for the permutation test. In each iteration (simulation), it samples nmemb nodes randomly among the entire nodes of the graph. Then, it tests the overlapped nodes among the randomly chosen nodes and the given node's neigborhood. At the end, it obtains an enrichment score for each simulation and evaluates these permuted enrichment scores with respect to the observed enrichment score of the hub. Among nsim random simulations; maximally, enrichment scores of 10 iterations are allowed to be greater than the observed (actual) enrichment score of the hub. If this limitation is exceeded, simulation will be finalized at that point and the enrichment score list of the iterations will be returned.

References

Shu L, Zhao Y, Kurt Z, Byars S, Tukiainen T, Kettunen J, Ripatti S, Zhang B, Inouye M, Makinen VP, Yang X. Mergeomics: integration of diverse genomics resources to identify pathogenic perturbations to biological systems. bioRxiv doi: http://dx.doi.org/10.1101/036012

See Also

kda.analyze, kda.analyze.exec, kda.analyze.test

Examples

job.kda <- list()
job.kda$label<-"HDLC"
## parent folder for results
job.kda$folder<-"Results"
## Input a network
## columns: TAIL HEAD WEIGHT
job.kda$netfile<-system.file("extdata","network.mouseliver.mouse.txt", 
package="Mergeomics")
## Gene sets derived from ModuleMerge, containing two columns, MODULE, 
## NODE, delimited by tab 
job.kda$modfile<- system.file("extdata","mergedModules.txt", 
package="Mergeomics")
## "0" means we do not consider edge weights while 1 is opposite.
job.kda$edgefactor<-0.0
## The searching depth for the KDA
job.kda$depth<-1
## 0 means we do not consider the directions of the regulatory interactions
## while 1 is opposite.
job.kda$direction<-1
job.kda$nperm <- 20 # the default value is 2000, use 20 for unit tests

## kda.start() process takes long time while seeking hubs in the given net
## Here, we used a very small subset of the module list (1st 10 mods
## from the original module file):
moddata <- tool.read(job.kda$modfile)
mod.names <- unique(moddata$MODULE)[1:min(length(unique(moddata$MODULE)),
10)]
moddata <- moddata[which(!is.na(match(moddata$MODULE, mod.names))),]
## save this to a temporary file and set its path as new job.kda$modfile:
tool.save(moddata, "subsetof.supersets.txt")
job.kda$modfile <- "subsetof.supersets.txt"

## Let's prepare KDA object for KDA:
job.kda <- kda.configure(job.kda)
job.kda <- kda.start(job.kda)
job.kda <- kda.prepare(job.kda)
set.seed(job.kda$seed)
i = 1 ## index of the module, whose p-val is calculated:
memb <- job.kda$module2nodes[[i]]
graph <- job.kda$graph  ## we need to import a network
nsim <- job.kda$nperm   ## number of simulations
## This auxiliary function is called by kda.analyze.exec(), which is called
## by kda.analyze() main function, see this main function for more details

hubs <- graph$hubs
hubnets <- graph$hubnets
nhubs <- length(hubs)
nnodes <- length(graph$nodes)
nmemb <- length(memb)
    
## Observed enrichment scores.
# obs <- rep(NA, nhubs)
# k <- 1 ## actual using: for(k in 1:nhubs){}, for unit test, use the 1st hub
# g <- hubnets[[hubs[k]]]
# obs[k] <- kda.analyze.test(g$RANK, g$STRENG, memb, nnodes)

## Estimate P-values.
# pvals <- rep(NA, nhubs)
# for(k in which(obs > 0)) {
# g <- hubnets[[hubs[k]]]
## First pass:
# x <- kda.analyze.simulate(obs[k], g, nmemb, nnodes, 200)
## Then, use x to estimate preliminary and final P-values. 
## See kda.analyze() for more detail

## Remove the temporary files used for the test:
file.remove("subsetof.supersets.txt")
## remove the results folder
unlink("Results", recursive = TRUE)
# } ## finishing for loop