kda.analyze: Weighted key driver analysis (wKDA) main function
In Mergeomics: Integrative network analysis of omics data

Description Usage Arguments Details Value Author(s) References See Also Examples

Finds the statistics (enrichment score, p-value, FDR, etc.) of the key driver (hub) genes belonging to the specified modules based on the graph topology. The enrichment score of a hub node based on the shared nodes between this hub's neighbor nodes in the graph and the member nodes of the hub's module. The hub node enrichment P-values reflect the degree of observed enrichment of the hub, when compared to the null distribution of randomly expected enrichment of this hub within graph's nodes. Permutation test is used to obtain these statistics.

1	kda.analyze(job)

job

The data list that will be subjected to KDA. It involves the modules, member genes belonging to each module, graph (network) topology, hubs of the graph, and sub-graph around each hub (hubnets of the graph).

kda.analyze analyzes each module individually and determines the p-values and FDRs of hub nodes of each module via permutation test. It returns the hit hub (key driver) gene name and member list of each module.

job

The KDA applied data list. It involves the modules, hub gene and member genes belonging to each module, and False Discovery Rate (FDR) adjusted p-values of hub nodes for each module.

Ville-Petteri Makinen

Shu L, Zhao Y, Kurt Z, Byars SG, Tukiainen T, Kettunen J, Orozco LD, Pellegrini M, Lusis AJ, Ripatti S, Zhang B, Inouye M, Makinen V-P, Yang X. Mergeomics: multidimensional data integration to identify pathogenic perturbations to biological systems. BMC genomics. 2016;17(1):874.

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

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 run KDA!

job.kda <- kda.configure(job.kda)
job.kda <- kda.start(job.kda)
job.kda <- kda.prepare(job.kda)
job.kda <- kda.analyze(job.kda)
job.kda <- kda.finish(job.kda)


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