In fgwinner/LEANR: Finds "Local Subnetworks" Within an Interaction Network which Show Enrichment for Differentially Expressed Genes

Run LEAN on the CCM data

Loading package and necessary data

library(LEANR)
set.seed(123456)
# load network and CCM p-values
data(g2)
data(CCM.pvals)
data(gene.annots)

library(LEANR)
set.seed(123456)
# load network and CCM p-values
data(g2)
data(CCM.pvals)
data(gene.annots)
LEAN_results<-LEANR:::LEAN_results

Run LEAN on the precomputed differential expression p-values (computed using limma) in turn for each of the three CCM gene knock-out experiments. As we run these calculations with background distributions of size 10.000, they will take a little time depending on how many cores are available on your machine.

LEAN_results<-lapply(names(CCM.pvals),function(ccm){
  run.lean(CCM.pvals[[ccm]], g2, n_reps = 10000, ncores = 3)
})
names(LEAN_results)<-names(CCM.pvals)

Extract significant local subnetworks in each of the three experiments and show which local subnetworks are significant in all three knock-out experiments

# Extract significant local subnetworks
sign.genes<-lapply(LEAN_results,function(LEANres){
  rownames(LEANres$restab[LEANres$restab[,'PLEAN']<=0.05,])
})
names(sign.genes)<-names(CCM.pvals)

# Show local subnetworks detected as significant in all three knock-outs
all.sign<-intersect(intersect(sign.genes[[1]],sign.genes[[2]]),sign.genes[[3]])
print(gene.annots[all.sign,])

The local subnetwork around VWF is the only one significant in all three knock-outs. Now we extract the local subnetwork around VWF and create a Cytoscape-readable subnetwork file

# Extract information on the detected local subnetwork (around VWF)
vwf.ls.info<-get.ls.info(all.sign[1],LEAN_results$CCM2)
print(head(vwf.ls.info))
write.table(vwf.ls.info,'./VWF_subnetwork_info_CCM2.txt',sep='\t',quote=F,row.names=F)

# Create sif file representing the local subnetwork around VWF
write.ls.to.sif(all.sign[1],LEAN_results$CCM2,'./VWF_subnetwork.sif')

After completing these steps, the local subnetwork around VWF can be inspected in Cytoscape by loading the network from file and adding information about the contained genes by loading the table from file

fgwinner/LEANR documentation built on May 16, 2019, 12:51 p.m.