GSE158422: DNA methylation in Lung squamous cell carcinoma - gene methylation enrichment analysis - sensitivity analysis
The GMEA team
2023-12-31
Introduction
In the previous analysis, it was shown that the limma-average-mitch (LAM) method yielded good performance with simulated data.
In this piece of work, we want to ascertain the sensitivity of this approach as compared to the existing method, GSAmeth.
To achieve this we will analyse with the full 37 patient sample pairs, and repeatedly downsample the dataset down to n=3 patients. What we expect is that LAM might have a higher degree of recall as compared to GSAmeth. We expect LAM will identify gene sets with larger effect sizes (enrichment scores) using fewer samples. This means that for a given set of datasets, this approach could yield more findings, or alternatively if pathway analysis is the primary outcome of a study, it need not be as large, which can save money and difficulty with establishing large sample collections.
Requirements
This analysis was run on a 16C/32T computer with 128GB RAM running at 4.2 GHz. RAM usage can be moderated by reducing the parallel core count.
This analysis was run on an AMD Ryzen Threadripper PRO 5955WX 16-Cores with 3200 MT/s DDR4.
suppressPackageStartupMessages({
library("limma")
library("eulerr")
library("IlluminaHumanMethylation450kmanifest")
library("IlluminaHumanMethylationEPICanno.ilm10b4.hg19")
library("HGNChelper")
library("tictoc")
library("mitch")
library("kableExtra")
library("beeswarm")
library("missMethyl")
library("gridExtra")
library("png")
})
CORES=16Load data
annotations
probe sets
gene sets
design matrix
mval matrix
anno <- getAnnotation(IlluminaHumanMethylationEPICanno.ilm10b4.hg19)
myann <- data.frame(anno[,c("UCSC_RefGene_Name","UCSC_RefGene_Group","Islands_Name","Relation_to_Island")])
gp <- myann[,"UCSC_RefGene_Name",drop=FALSE]
gp2 <- strsplit(gp$UCSC_RefGene_Name,";")
names(gp2) <- rownames(gp)
gp2 <- lapply(gp2,unique)
gt <- stack(gp2)
colnames(gt) <- c("gene","probe")
dim(gt)## [1] 684970 2str(gt)## 'data.frame': 684970 obs. of 2 variables:
## $ gene : chr "YTHDF1" "EIF2S3" "PKN3" "CCDC57" ...
## $ probe: Factor w/ 865859 levels "cg18478105","cg09835024",..: 1 2 3 4 5 6 7 8 8 9 ...head(gt)## gene probe
## 1 YTHDF1 cg18478105
## 2 EIF2S3 cg09835024
## 3 PKN3 cg14361672
## 4 CCDC57 cg01763666
## 5 INF2 cg12950382
## 6 CDC16 cg02115394#new.hgnc.table <- getCurrentHumanMap()
new.hgnc.table <- readRDS("new.hgnc.table.rds")
fix <- checkGeneSymbols(gt$gene,map=new.hgnc.table)## Warning in checkGeneSymbols(gt$gene, map = new.hgnc.table): Human gene symbols
## should be all upper-case except for the 'orf' in open reading frames. The case
## of some letters was corrected.## Warning in checkGeneSymbols(gt$gene, map = new.hgnc.table): x contains
## non-approved gene symbolsfix2 <- fix[which(fix$x != fix$Suggested.Symbol),]
length(unique(fix2$x))## [1] 3253gt$gene <- fix$Suggested.Symbol
gp <- myann[,"UCSC_RefGene_Name",drop=FALSE]
gp2 <- strsplit(gp$UCSC_RefGene_Name,";")
names(gp2) <- rownames(gp)
sets <- split(rep(names(gp2), lengths(gp2)), unlist(gp2))
summary(unlist(lapply(sets,length)))## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 1.00 9.00 24.00 49.68 55.00 6778.00if (!file.exists("GSE158422_design.rds")) {
download.file("https://ziemann-lab.net/public/gmea_prototype/GSE158422_design.rds", "GSE158422_design.rds")
}
design <- readRDS("GSE158422_design.rds")
if (!file.exists("GSE158422_design.rds")) {
download.file("https://ziemann-lab.net/public/gmea_prototype/GSE158422_mx.rds","GSE158422_mx.rds")
}
mval <- readRDS("GSE158422_mx.rds")
mval_means <- list("tumor"=matrix(colMeans(mval),ncol=2)[,1],"normal"=matrix(colMeans(mval),ncol=2)[,2])
boxplot(mval_means, main="mean probe methylation mval",cex=0,col="white")
beeswarm(mval_means,add=TRUE,pch=1,cex=1.5)
lapply(mval_means,mean)## $tumor
## [1] -0.1362266
##
## $normal
## [1] -0.1228003We will assume mean probe methylation is a proxy measure for global methylation. The boxplot appears to show higher values in tumour samples, based on median and quartiles. However the mean values are actually lower in tumour samples compared to normal.
Reactome pathways were downloaded on the 14th Sept 2023 from MsigDB.
gs_entrez <- gmt_import("c2.cp.reactome.v2023.1.Hs.entrez.gmt")
gs_symbols <- gmt_import("c2.cp.reactome.v2023.1.Hs.symbols.gmt")AL GMEA: all probes
Start with curating the sample info and design matrix.
sex <- as.data.frame(design)$sex
tumor <- as.data.frame(design)$tumor
patient <- as.character(unlist(lapply(1:ncol(mval),function(i) {c(i,i)})))
patient <- head(patient,ncol(mval))
design <- model.matrix(~ patient + tumor )Functions
limma-average-mitch (LAM).
# limma
runlimma <- function(mval,design,myann) {
fit.reduced <- lmFit(mval,design)
fit.reduced <- eBayes(fit.reduced)
dm <- topTable(fit.reduced,coef=ncol(design), number = Inf)
dm <- merge(myann,dm,by=0)
dm <- dm[order(dm$P.Value),]
rownames(dm) <- dm$Row.names
dm$Row.names=NULL
return(dm)
}Function to run mitch analysis.
runmitch <- function(m,genesets,cores=1) {
suppressMessages({ mres <- mitch_calc(m,genesets,minsetsize=5,cores=cores, priority="effect") })
mres <- mres$enrichment_result
rownames(mres) <- mres$set
mres$set=NULL
return(mres)
}Run limma
Run limma and look at the absolute effect sizes.
dim(mval)## [1] 839473 74dim(design)## [1] 74 38tic()
dm <- runlimma(mval=mval,design=design,myann=myann)
toc() ## mean(23.7 26.8 25.4)=23.7## 34.079 sec elapsedtop <- head(dm,20)
top <- top[order(top$logFC),]
dim(dm)## [1] 839473 10nrow(subset(dm,adj.P.Val<0.05 & logFC>0))## [1] 118991nrow(subset(dm,adj.P.Val<0.05 & logFC<0))## [1] 356521saveRDS(dm,"GSE158422_dm.rds")
length(unique(unlist(strsplit(subset(dm,adj.P.Val<0.05 & logFC>0)$UCSC_RefGene_Name,";"))))## [1] 16470length(unique(unlist(strsplit(subset(dm,adj.P.Val<0.05 & logFC<0)$UCSC_RefGene_Name,";"))))## [1] 24150length(unique(unlist(strsplit(dm$UCSC_RefGene_Name,";"))))## [1] 26219par(mfrow=c(3,1))
sig <- head(subset(dm,adj.P.Val < 0.05 ),100)
sigmval <- mval[rownames(mval) %in% rownames(sig),]
es <- lapply(1:nrow(sigmval), function(i) {
x <- sigmval[i,]
mx <- matrix(x,ncol=2)
cancer <- median(mx[,1])
normal <- median(mx[,2])
abs(cancer-normal)
} )
hist(unlist(es),main="top 100 probes", xlab="probe effect size")
summary(unlist(es))## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.01245 0.08495 0.16424 0.19353 0.27575 0.67492sig <- head(subset(dm,adj.P.Val < 0.05 ),1000)
sig <- sig[101:1000,]
sigmval <- mval[rownames(mval) %in% rownames(sig),]
es <- lapply(1:nrow(sigmval), function(i) {
x <- sigmval[i,]
mx <- matrix(x,ncol=2)
cancer <- median(mx[,1])
normal <- median(mx[,2])
abs(cancer-normal)
} )
hist(unlist(es),main="top 1000 probes ex top 100", xlab="probe effect size")
summary(unlist(es))## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.000289 0.062551 0.127262 0.166881 0.232781 0.777504sig <- head(subset(dm,adj.P.Val < 0.05 ),10000)
sig <- sig[1001:10000,]
sigmval <- mval[rownames(mval) %in% rownames(sig),]
es <- lapply(1:nrow(sigmval), function(i) {
x <- sigmval[i,]
mx <- matrix(x,ncol=2)
cancer <- median(mx[,1])
normal <- median(mx[,2])
abs(cancer-normal)
} )
hist(unlist(es), main="top 10000 probes ex top 1000", xlab="probe effect size")
summary(unlist(es))## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.0000134 0.0500710 0.1082088 0.1367342 0.1908561 1.2846813par(mfrow=c(1,1))Run LAM
Run LAM method on tumour-normal methylation data. Record timings.
tic()
dd <- merge(dm,gt,by.x=0,by.y="probe")
m <- aggregate(t ~ gene,dd,mean)
rownames(m) <- m$gene
m$gene=NULL
lamres <- runmitch(m=m,genesets=gs_symbols,cores=8)
toc()## 51.473 sec elapsedtop %>%
kbl(caption="Top significant probes") %>%
kable_paper("hover", full_width = F)| UCSC_RefGene_Name | UCSC_RefGene_Group | Islands_Name | Relation_to_Island | logFC | AveExpr | t | P.Value | adj.P.Val | B | |
|---|---|---|---|---|---|---|---|---|---|---|
| cg12279138 | DEGS1;DEGS1 | TSS1500;TSS1500 | chr1:224370585-224371755 | N_Shore | -1.989078 | -1.8410416 | -12.86720 | 0 | 0 | 25.75728 |
| cg17094249 | OpenSea | -1.709132 | -1.5401158 | -13.50069 | 0 | 0 | 27.25684 | |||
| cg13327911 | COL21A1 | Body | OpenSea | -1.700022 | -2.5247476 | -12.85931 | 0 | 0 | 25.73828 | |
| cg00159780 | REXO1L2P;REXO1L1 | Body;1stExon | chr8:86573421-86575248 | Island | -1.679439 | 1.1191349 | -12.98468 | 0 | 0 | 26.03936 |
| cg02084219 | HIVEP3;HIVEP3 | 5’UTR;5’UTR | OpenSea | -1.672335 | -1.6009059 | -13.44860 | 0 | 0 | 27.13552 | |
| cg17160384 | CCNB1 | TSS200 | chr5:68462675-68463214 | Island | -1.376384 | -3.3207907 | -12.88233 | 0 | 0 | 25.79372 |
| cg27014672 | LZTS2 | TSS1500 | chr10:102756834-102759798 | N_Shore | -1.369554 | -1.5900277 | -12.97163 | 0 | 0 | 26.00812 |
| cg01772014 | C20orf160 | Body | chr20:30606492-30607174 | N_Shore | -1.259530 | -2.1184692 | -12.93201 | 0 | 0 | 25.91313 |
| cg00718470 | chr15:98964607-98965369 | Island | -1.216445 | -2.9756305 | -12.64503 | 0 | 0 | 25.21880 | ||
| cg08365845 | GNAI2;GNAI2 | 5’UTR;Body | chr3:50264402-50265101 | S_Shore | -1.135956 | -3.7589600 | -13.15271 | 0 | 0 | 26.43965 |
| cg14205001 | NOTCH1 | Body | chr9:139405089-139405292 | S_Shore | 1.059931 | 1.0214777 | 12.55143 | 0 | 0 | 24.98995 |
| cg02655980 | GALK2;GALK2;GALK2;MIR4716;GALK2 | TSS1500;TSS1500;TSS1500;TSS200;Body | OpenSea | 1.140557 | 1.9480502 | 13.01611 | 0 | 0 | 26.11453 | |
| cg17627973 | SRPK2;SRPK2 | Body;Body | chr7:104885049-104885400 | Island | 1.230248 | 1.4815710 | 13.21441 | 0 | 0 | 26.58569 |
| cg12131862 | ATP2B4;ATP2B4 | 5’UTR;5’UTR | OpenSea | 1.321145 | 1.1544277 | 12.78071 | 0 | 0 | 25.54844 | |
| cg09067993 | SUCLG2;SUCLG2 | Body;Body | OpenSea | 1.673953 | 1.0594170 | 12.70686 | 0 | 0 | 25.36931 | |
| cg09307985 | COX7A1 | Body | chr19:36642327-36643585 | Island | 1.832151 | 0.5034749 | 12.68295 | 0 | 0 | 25.31118 |
| cg26521404 | HOXA9 | 1stExon | chr7:27203915-27206462 | Island | 2.389439 | -2.1024739 | 12.56224 | 0 | 0 | 25.01644 |
| cg09792881 | DMRTA2 | Body | chr1:50884228-50891471 | Island | 2.655918 | -2.3970154 | 13.91557 | 0 | 0 | 28.21067 |
| cg10512745 | DMRTA2 | Body | chr1:50884228-50891471 | Island | 2.939006 | -2.6631580 | 13.79397 | 0 | 0 | 27.93339 |
| cg16732616 | DMRTA2 | Body | chr1:50884228-50891471 | Island | 3.036097 | -2.2858078 | 13.61793 | 0 | 0 | 27.52861 |
lamsig <- subset(lamres,p.adjustANOVA<0.05)
topup <- subset(lamres,p.adjustANOVA<0.05 & s.dist >0 )
topup <- tail(topup[order(topup$s.dist),],10)
topdn <- subset(lamres,p.adjustANOVA<0.05 & s.dist <0 )
topdn <- head(topdn[order(topdn$s.dist),],10)
topup %>%
kbl(caption="Top gene sets hypermethylated (biggest effect size with FDR<0.05)") %>%
kable_paper("hover", full_width = F)| setSize | pANOVA | s.dist | p.adjustANOVA | |
|---|---|---|---|---|
| REACTOME_ADRENOCEPTORS | 9 | 0.0033578 | 0.5645332 | 0.0174123 |
| REACTOME_REGULATION_OF_GENE_EXPRESSION_BY_HYPOXIA_INDUCIBLE_FACTOR | 11 | 0.0007914 | 0.5842663 | 0.0054374 |
| REACTOME_REGULATION_OF_GENE_EXPRESSION_IN_LATE_STAGE_BRANCHING_MORPHOGENESIS_PANCREATIC_BUD_PRECURSOR_CELLS | 15 | 0.0000791 | 0.5885342 | 0.0007967 |
| REACTOME_POU5F1_OCT4_SOX2_NANOG_REPRESS_GENES_RELATED_TO_DIFFERENTIATION | 10 | 0.0012394 | 0.5897449 | 0.0077708 |
| REACTOME_INTERLEUKIN_9_SIGNALING | 7 | 0.0065626 | 0.5932492 | 0.0299328 |
| REACTOME_VITAMINS | 6 | 0.0061180 | 0.6462191 | 0.0281394 |
| REACTOME_ENDOSOMAL_VACUOLAR_PATHWAY | 11 | 0.0001780 | 0.6526069 | 0.0016056 |
| REACTOME_FBXW7_MUTANTS_AND_NOTCH1_IN_CANCER | 5 | 0.0091909 | 0.6726357 | 0.0394033 |
| REACTOME_FORMATION_OF_LATERAL_PLATE_MESODERM | 5 | 0.0007632 | 0.8690826 | 0.0052877 |
| REACTOME_REGULATION_OF_GENE_EXPRESSION_IN_EARLY_PANCREATIC_PRECURSOR_CELLS | 8 | 0.0000147 | 0.8845635 | 0.0001773 |
topdn %>%
kbl(caption="Top gene sets hypomethylated (biggest effect size with FDR<0.05)") %>%
kable_paper("hover", full_width = F)| setSize | pANOVA | s.dist | p.adjustANOVA | |
|---|---|---|---|---|
| REACTOME_OLFACTORY_SIGNALING_PATHWAY | 372 | 0.0000000 | -0.8206464 | 0.0000000 |
| REACTOME_BETA_DEFENSINS | 37 | 0.0000000 | -0.8131265 | 0.0000000 |
| REACTOME_METAL_SEQUESTRATION_BY_ANTIMICROBIAL_PROTEINS | 6 | 0.0006164 | -0.8071625 | 0.0044586 |
| REACTOME_DIGESTION_OF_DIETARY_CARBOHYDRATE | 10 | 0.0000109 | -0.8031649 | 0.0001354 |
| REACTOME_CD22_MEDIATED_BCR_REGULATION | 5 | 0.0030226 | -0.7657239 | 0.0162491 |
| REACTOME_DEFENSINS | 46 | 0.0000000 | -0.7633479 | 0.0000000 |
| REACTOME_MELANIN_BIOSYNTHESIS | 5 | 0.0060191 | -0.7092629 | 0.0277815 |
| REACTOME_ANTIMICROBIAL_PEPTIDES | 89 | 0.0000000 | -0.6729801 | 0.0000000 |
| REACTOME_AMINO_ACID_CONJUGATION | 9 | 0.0006921 | -0.6530037 | 0.0049198 |
| REACTOME_BIOSYNTHESIS_OF_MARESIN_LIKE_SPMS | 6 | 0.0093512 | -0.6126457 | 0.0396761 |
top <- rbind(topdn,topup)
barnames <- gsub("_"," ",gsub("REACTOME_","",rownames(top)))
cols <- gsub("TRUE","red",gsub("FALSE","blue",as.character(top$s.dist>0)))
par(mar = c(5.1, 29.1, 4.1, 2.1))
barplot(abs(top$s.dist),horiz=TRUE,las=1,names.arg=barnames, cex.names=0.65,
cex.axis=0.8,col=cols, xlab="Enrichment score",main="Reactomes")
grid()
par( mar = c(5.1, 4.1, 4.1, 2.1) )
hist(lamsig$s.dist)
# distinguish up (TRUE) and down (FALSE)
lamsigsets <- paste(rownames(lamsig),as.character(lamsig$s.dist > 0))
lamsigsets2 <- gsub(" TRUE"," UP",lamsigsets)
lamsigsets2 <- gsub(" FALSE"," DN",lamsigsets2)Downsample LAM test
This will run the LAM analysis at group sizes of 2, 3, 6, 10, 16, 22 and 30, 50 times each, with pseudorandom seeds from 100 to 5000 jumping up by 100.
SAMPLESIZES=c(2,3,6,10,16,22,30)
ssres <- lapply(SAMPLESIZES,function(n) {
SEEDS <- seq(100,5000,100)
dsres <- mclapply(SEEDS, function(SEED) {
set.seed(SEED)
mysample <- sample(1:37,n,replace=FALSE)*2
mysample <- c(mysample,(mysample-1))
mysample <- mysample[order(mysample)]
design2 <- design[mysample,]
design2 <- design2[,colSums(design2)>0]
mval2 <- mval[,mysample]
dm2 <- runlimma(mval=mval2,design=design2,myann=myann)
dd <- merge(dm2,gt,by.x=0,by.y="probe")
m2 <- aggregate(t ~ gene,dd,mean)
rownames(m2) <- m2$gene
m2$gene=NULL
lamres2 <- runmitch(m=m2,genesets=gs_symbols,cores=2)
lamsig2 <- subset(lamres2,p.adjustANOVA<0.05)
lamsigsets2 <- paste(rownames(lamsig2),as.character(lamsig2$s.dist > 0))
TOT=length(lamsigsets2)
TP=length(which(lamsigsets2 %in% lamsigsets))
FP=length(which(!lamsigsets2 %in% lamsigsets))
FN=length(which(!lamsigsets %in% lamsigsets2))
RES=c("TOT"=TOT,"TP"=TP,"FP"=FP,"FN"=FN)
RES
},mc.cores=5)
do.call(rbind,dsres)
})
par(mfrow=c(3,1))
dots <- lapply(ssres,function(x) { x[,"TP"] })
lapply(dots,summary)## [[1]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 4.0 98.0 169.5 190.5 319.5 384.0
##
## [[2]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 20.0 135.5 212.0 226.4 348.5 385.0
##
## [[3]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 38.0 187.0 318.5 274.4 370.8 397.0
##
## [[4]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 118.0 297.2 354.5 332.2 387.8 397.0
##
## [[5]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 228.0 335.2 373.0 355.3 390.5 401.0
##
## [[6]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 265.0 345.5 379.5 368.6 396.0 406.0
##
## [[7]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 326.0 376.8 398.0 388.5 403.0 406.0boxplot(dots,names=SAMPLESIZES,col="white",ylab="no. true positives",xlab="sample size",cex=0,main="LAM") ; grid()
beeswarm(dots,add=TRUE,pch=1,cex=0.6)
abline(h=nrow(lamsig))
dots <- lapply(ssres,function(x) { x[,"FP"] })
lapply(dots,summary)## [[1]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 2.00 18.00 49.00 79.72 98.00 332.00
##
## [[2]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 3.00 12.50 51.50 75.76 95.50 326.00
##
## [[3]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 3.00 14.25 38.50 67.96 87.00 353.00
##
## [[4]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 3.00 13.25 37.00 66.42 86.50 289.00
##
## [[5]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 2.00 11.00 29.50 49.52 69.50 241.00
##
## [[6]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 2.00 8.00 16.00 35.72 49.75 139.00
##
## [[7]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 1.00 6.00 20.50 25.70 40.25 74.00boxplot(dots,names=SAMPLESIZES,col="white",ylab="no. false positives",xlab="sample size",cex=0) ; grid()
beeswarm(dots,add=TRUE,pch=1,cex=0.6)
dots <- lapply(ssres,function(x) { x[,"TP"] })
TPdots <- do.call(rbind,dots)
dots <- lapply(ssres,function(x) { x[,"FP"] })
FPdots <- do.call(rbind,dots)
ratio <- t(FPdots / (TPdots + FPdots))
ratio <- lapply(1:ncol(ratio),function(i) {ratio[,i]})
lapply(ratio,summary)## [[1]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.01449 0.15644 0.23385 0.28769 0.41270 0.92958
##
## [[2]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.03185 0.11557 0.17278 0.22316 0.26997 0.88701
##
## [[3]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.02778 0.06468 0.12870 0.16172 0.22590 0.47917
##
## [[4]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.009288 0.044012 0.099488 0.135913 0.181221 0.426883
##
## [[5]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.00623 0.03191 0.07053 0.10241 0.14831 0.37539
##
## [[6]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.005556 0.023342 0.041778 0.077930 0.113490 0.256458
##
## [[7]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.002611 0.015867 0.048515 0.058139 0.090643 0.154167boxplot(ratio,names=SAMPLESIZES,col="white",ylab="proportion FP",xlab="sample size",cex=0) ; grid()
beeswarm(ratio,add=TRUE,pch=1,cex=0.6)
par(mfrow=c(1,1))GSAMETH
Run GSA meth on the full dataset.
dm <- runlimma(mval,design,myann)
hist(dm$t,breaks=100,xlim=c(-10,10)) ; grid()
head(dm, 10) %>% kbl(caption="Top 10 probes by p-value") %>% kable_paper("hover", full_width = F)| UCSC_RefGene_Name | UCSC_RefGene_Group | Islands_Name | Relation_to_Island | logFC | AveExpr | t | P.Value | adj.P.Val | B | |
|---|---|---|---|---|---|---|---|---|---|---|
| cg09792881 | DMRTA2 | Body | chr1:50884228-50891471 | Island | 2.655918 | -2.397015 | 13.91557 | 0 | 0 | 28.21067 |
| cg10512745 | DMRTA2 | Body | chr1:50884228-50891471 | Island | 2.939006 | -2.663158 | 13.79397 | 0 | 0 | 27.93339 |
| cg16732616 | DMRTA2 | Body | chr1:50884228-50891471 | Island | 3.036097 | -2.285808 | 13.61793 | 0 | 0 | 27.52861 |
| cg17094249 | OpenSea | -1.709132 | -1.540116 | -13.50069 | 0 | 0 | 27.25684 | |||
| cg02084219 | HIVEP3;HIVEP3 | 5’UTR;5’UTR | OpenSea | -1.672335 | -1.600906 | -13.44860 | 0 | 0 | 27.13552 | |
| cg17627973 | SRPK2;SRPK2 | Body;Body | chr7:104885049-104885400 | Island | 1.230248 | 1.481571 | 13.21441 | 0 | 0 | 26.58569 |
| cg08365845 | GNAI2;GNAI2 | 5’UTR;Body | chr3:50264402-50265101 | S_Shore | -1.135956 | -3.758960 | -13.15271 | 0 | 0 | 26.43965 |
| cg02655980 | GALK2;GALK2;GALK2;MIR4716;GALK2 | TSS1500;TSS1500;TSS1500;TSS200;Body | OpenSea | 1.140557 | 1.948050 | 13.01611 | 0 | 0 | 26.11453 | |
| cg00159780 | REXO1L2P;REXO1L1 | Body;1stExon | chr8:86573421-86575248 | Island | -1.679439 | 1.119135 | -12.98468 | 0 | 0 | 26.03936 |
| cg27014672 | LZTS2 | TSS1500 | chr10:102756834-102759798 | N_Shore | -1.369554 | -1.590028 | -12.97163 | 0 | 0 | 26.00812 |
sizes=c(1000,5000,10000,20000,50000,100000,200000,300000,350000,400000,450000,500000)
nsigs <- lapply(sizes, function(z) {
dmsig <- head(dm,z)
dmsigup <- rownames(subset(dmsig,logFC>0))
dmsigdn <- rownames(subset(dmsig,logFC<0))
gsaup <- gsameth(sig.cpg=dmsigup, all.cpg=rownames(dm), collection=gs_entrez, array.type="EPIC")
rownames(gsaup) <- paste(rownames(gsaup),"UP")
gsadn <- gsameth(sig.cpg=dmsigdn, all.cpg=rownames(dm), collection=gs_entrez, array.type="EPIC")
rownames(gsadn) <- paste(rownames(gsadn),"DN")
nsig <- rownames(subset(rbind(gsaup,gsadn),FDR<0.05))
return(nsig)
})## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.names(nsigs) <- sizes
str(nsigs)## List of 12
## $ 1000 : chr(0)
## $ 5000 : chr [1:2] "REACTOME_RHOB_GTPASE_CYCLE UP" "REACTOME_RHOC_GTPASE_CYCLE UP"
## $ 10000 : chr [1:2] "REACTOME_RHOB_GTPASE_CYCLE UP" "REACTOME_RHOC_GTPASE_CYCLE UP"
## $ 20000 : chr [1:3] "REACTOME_DISEASES_OF_SIGNAL_TRANSDUCTION_BY_GROWTH_FACTOR_RECEPTORS_AND_SECOND_MESSENGERS UP" "REACTOME_RHOC_GTPASE_CYCLE UP" "REACTOME_OLFACTORY_SIGNALING_PATHWAY DN"
## $ 50000 : chr [1:9] "REACTOME_DISEASES_OF_SIGNAL_TRANSDUCTION_BY_GROWTH_FACTOR_RECEPTORS_AND_SECOND_MESSENGERS UP" "REACTOME_RHOA_GTPASE_CYCLE UP" "REACTOME_RHO_GTPASE_CYCLE UP" "REACTOME_RHOB_GTPASE_CYCLE UP" ...
## $ 1e+05 : chr [1:17] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_PLURIPOTENT_STEM_CELLS UP" "REACTOME_DISEASES_OF_SIGNAL_TRANSDUCTION_BY_GROWTH_FACTOR_RECEPTORS_AND_SECOND_MESSENGERS UP" "REACTOME_RHOA_GTPASE_CYCLE UP" "REACTOME_RHO_GTPASE_CYCLE UP" ...
## $ 2e+05 : chr [1:28] "REACTOME_NEURONAL_SYSTEM UP" "REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION UP" "REACTOME_NEF_MEDIATES_DOWN_MODULATION_OF_CELL_SURFACE_RECEPTORS_BY_RECRUITING_THEM_TO_CLATHRIN_ADAPTERS UP" "REACTOME_THE_ROLE_OF_NEF_IN_HIV_1_REPLICATION_AND_DISEASE_PATHOGENESIS UP" ...
## $ 3e+05 : chr [1:52] "REACTOME_HEMOSTASIS UP" "REACTOME_OPIOID_SIGNALLING UP" "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP" "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION UP" ...
## $ 350000: chr [1:79] "REACTOME_HEMOSTASIS UP" "REACTOME_OPIOID_SIGNALLING UP" "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP" "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION UP" ...
## $ 4e+05 : chr [1:79] "REACTOME_HEMOSTASIS UP" "REACTOME_OPIOID_SIGNALLING UP" "REACTOME_CA_DEPENDENT_EVENTS UP" "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP" ...
## $ 450000: chr [1:94] "REACTOME_HEMOSTASIS UP" "REACTOME_OPIOID_SIGNALLING UP" "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP" "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION UP" ...
## $ 5e+05 : chr [1:137] "REACTOME_HEMOSTASIS UP" "REACTOME_OPIOID_SIGNALLING UP" "REACTOME_CA_DEPENDENT_EVENTS UP" "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP" ...lapply(nsigs,length)## $`1000`
## [1] 0
##
## $`5000`
## [1] 2
##
## $`10000`
## [1] 2
##
## $`20000`
## [1] 3
##
## $`50000`
## [1] 9
##
## $`1e+05`
## [1] 17
##
## $`2e+05`
## [1] 28
##
## $`3e+05`
## [1] 52
##
## $`350000`
## [1] 79
##
## $`4e+05`
## [1] 79
##
## $`450000`
## [1] 94
##
## $`5e+05`
## [1] 137par( mar = c(5.1, 6.1, 4.1, 2.1) )
barplot(unlist(lapply(nsigs,length)),horiz=TRUE,las=1,xlab="no. significant sets") ; grid()
mtext("no. probes selected", 2, 4)
#
FCLIM <- c(0,0.1,0.2,0.3,0.4,0.5,0.6,0.7,0.8,0.9,1)
ngsig <- lapply(FCLIM,function(F) {
sigup <- rownames(subset(dm,logFC > F & adj.P.Val < 0.05))
sigdn <- rownames(subset(dm,logFC < -F & adj.P.Val < 0.05))
gsaup <- gsameth(sig.cpg=sigup, all.cpg=rownames(dm), collection=gs_entrez, array.type="EPIC")
rownames(gsaup) <- paste(rownames(gsaup),"UP")
gsadn <- gsameth(sig.cpg=sigdn, all.cpg=rownames(dm), collection=gs_entrez, array.type="EPIC")
rownames(gsadn) <- paste(rownames(gsadn),"DN")
ngsig <- rownames(subset(rbind(gsaup,gsadn),FDR<0.05))
return(ngsig)
})## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.
## All input CpGs are used for testing.names(ngsig) <- FCLIM
str(ngsig)## List of 11
## $ 0 : chr [1:107] "REACTOME_HEMOSTASIS UP" "REACTOME_OPIOID_SIGNALLING UP" "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP" "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION UP" ...
## $ 0.1: chr [1:107] "REACTOME_HEMOSTASIS UP" "REACTOME_OPIOID_SIGNALLING UP" "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP" "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION UP" ...
## $ 0.2: chr [1:101] "REACTOME_HEMOSTASIS UP" "REACTOME_OPIOID_SIGNALLING UP" "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP" "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION UP" ...
## $ 0.3: chr [1:100] "REACTOME_HEMOSTASIS UP" "REACTOME_OPIOID_SIGNALLING UP" "REACTOME_CA_DEPENDENT_EVENTS UP" "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP" ...
## $ 0.4: chr [1:94] "REACTOME_HEMOSTASIS UP" "REACTOME_OPIOID_SIGNALLING UP" "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP" "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION UP" ...
## $ 0.5: chr [1:62] "REACTOME_HEMOSTASIS UP" "REACTOME_OPIOID_SIGNALLING UP" "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP" "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION UP" ...
## $ 0.6: chr [1:42] "REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES UP" "REACTOME_NEURONAL_SYSTEM UP" "REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION UP" "REACTOME_CELL_CELL_COMMUNICATION UP" ...
## $ 0.7: chr [1:25] "REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES UP" "REACTOME_NEURONAL_SYSTEM UP" "REACTOME_SIGNALING_BY_GPCR UP" "REACTOME_NEPHRIN_FAMILY_INTERACTIONS UP" ...
## $ 0.8: chr [1:19] "REACTOME_DEVELOPMENTAL_BIOLOGY UP" "REACTOME_REGULATION_OF_BETA_CELL_DEVELOPMENT UP" "REACTOME_SIGNALING_BY_GPCR UP" "REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS UP" ...
## $ 0.9: chr [1:21] "REACTOME_REGULATION_OF_BETA_CELL_DEVELOPMENT UP" "REACTOME_REGULATION_OF_GENE_EXPRESSION_IN_EARLY_PANCREATIC_PRECURSOR_CELLS UP" "REACTOME_SIGNALING_BY_GPCR UP" "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION DN" ...
## $ 1 : chr [1:20] "REACTOME_DEVELOPMENTAL_BIOLOGY UP" "REACTOME_REGULATION_OF_BETA_CELL_DEVELOPMENT UP" "REACTOME_REGULATION_OF_GENE_EXPRESSION_IN_EARLY_PANCREATIC_PRECURSOR_CELLS UP" "REACTOME_SIGNALING_BY_GPCR UP" ...lapply(ngsig,length)## $`0`
## [1] 107
##
## $`0.1`
## [1] 107
##
## $`0.2`
## [1] 101
##
## $`0.3`
## [1] 100
##
## $`0.4`
## [1] 94
##
## $`0.5`
## [1] 62
##
## $`0.6`
## [1] 42
##
## $`0.7`
## [1] 25
##
## $`0.8`
## [1] 19
##
## $`0.9`
## [1] 21
##
## $`1`
## [1] 20par( mar = c(5.1, 6.1, 4.1, 2.1) )
barplot(unlist(lapply(ngsig,length)),horiz=TRUE,las=1,xlab="no. significant sets") ; grid()
mtext("fold change threshold", 2, 4)
sigup <- rownames(subset(dm,logFC > 0 & adj.P.Val < 0.05))
sigdn <- rownames(subset(dm,logFC < 0 & adj.P.Val < 0.05))
tic()
gsaup <- gsameth(sig.cpg=sigup, all.cpg=rownames(dm), collection=gs_entrez, array.type="EPIC")## All input CpGs are used for testing.rownames(gsaup) <- paste(rownames(gsaup),"UP")
gsadn <- gsameth(sig.cpg=sigdn, all.cpg=rownames(dm), collection=gs_entrez, array.type="EPIC")## All input CpGs are used for testing.rownames(gsadn) <- paste(rownames(gsadn),"DN")
toc() # 12.9, 12.6, 11.5## 21.972 sec elapsedgsaup <- gsaup[order(gsaup$P.DE),]
gsadn <- gsadn[order(gsadn$P.DE),]
gsig_up <- subset(gsaup,FDR<0.05)
head(gsig_up,20) %>% kbl(caption="Hypermethylated pathways") %>% kable_paper("hover", full_width = F)| N | DE | P.DE | FDR | |
|---|---|---|---|---|
| REACTOME_NEURONAL_SYSTEM UP | 388 | 343 | 0.00e+00 | 0.0000000 |
| REACTOME_SIGNALING_BY_RECEPTOR_TYROSINE_KINASES UP | 509 | 440 | 0.00e+00 | 0.0000000 |
| REACTOME_RHO_GTPASE_CYCLE UP | 425 | 372 | 0.00e+00 | 0.0000001 |
| REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION UP | 292 | 257 | 0.00e+00 | 0.0000005 |
| REACTOME_CDC42_GTPASE_CYCLE UP | 145 | 136 | 0.00e+00 | 0.0000061 |
| REACTOME_SIGNALING_BY_GPCR UP | 679 | 532 | 0.00e+00 | 0.0000061 |
| REACTOME_RAC1_GTPASE_CYCLE UP | 173 | 159 | 1.00e-07 | 0.0000174 |
| REACTOME_DISEASES_OF_SIGNAL_TRANSDUCTION_BY_GROWTH_FACTOR_RECEPTORS_AND_SECOND_MESSENGERS UP | 418 | 352 | 3.00e-07 | 0.0000666 |
| REACTOME_SIGNALING_BY_RHO_GTPASES_MIRO_GTPASES_AND_RHOBTB3 UP | 677 | 549 | 6.00e-07 | 0.0001066 |
| REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES UP | 255 | 221 | 1.00e-06 | 0.0001579 |
| REACTOME_GLYCOSAMINOGLYCAN_METABOLISM UP | 118 | 108 | 1.00e-06 | 0.0001579 |
| REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS UP | 206 | 172 | 3.20e-06 | 0.0004427 |
| REACTOME_RHOA_GTPASE_CYCLE UP | 142 | 129 | 4.40e-06 | 0.0005631 |
| REACTOME_POTASSIUM_CHANNELS UP | 102 | 93 | 9.20e-06 | 0.0010841 |
| REACTOME_ECM_PROTEOGLYCANS UP | 73 | 69 | 1.61e-05 | 0.0017756 |
| REACTOME_DEATH_RECEPTOR_SIGNALING UP | 144 | 127 | 2.69e-05 | 0.0027850 |
| REACTOME_INTEGRATION_OF_ENERGY_METABOLISM UP | 105 | 95 | 2.91e-05 | 0.0028311 |
| REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION UP | 250 | 209 | 3.36e-05 | 0.0030835 |
| REACTOME_HEMOSTASIS UP | 598 | 472 | 4.61e-05 | 0.0039324 |
| REACTOME_DEGRADATION_OF_THE_EXTRACELLULAR_MATRIX UP | 135 | 118 | 4.75e-05 | 0.0039324 |
gsig_dn <- subset(gsadn,FDR<0.05)
head(gsig_dn,20) %>% kbl(caption="Hypomethylated pathways") %>% kable_paper("hover", full_width = F)| N | DE | P.DE | FDR | |
|---|---|---|---|---|
| REACTOME_METABOLISM_OF_LIPIDS DN | 711 | 704 | 0.0000000 | 0.0000000 |
| REACTOME_INNATE_IMMUNE_SYSTEM DN | 1027 | 1006 | 0.0000000 | 0.0000001 |
| REACTOME_TRANSPORT_OF_SMALL_MOLECULES DN | 696 | 684 | 0.0000000 | 0.0000096 |
| REACTOME_ADAPTIVE_IMMUNE_SYSTEM DN | 737 | 723 | 0.0000000 | 0.0000096 |
| REACTOME_SENSORY_PERCEPTION DN | 578 | 565 | 0.0000000 | 0.0000135 |
| REACTOME_HEMOSTASIS DN | 598 | 585 | 0.0000027 | 0.0007167 |
| REACTOME_RHO_GTPASE_CYCLE DN | 425 | 419 | 0.0000030 | 0.0007167 |
| REACTOME_OLFACTORY_SIGNALING_PATHWAY DN | 371 | 362 | 0.0000037 | 0.0007173 |
| REACTOME_NEURONAL_SYSTEM DN | 388 | 383 | 0.0000039 | 0.0007173 |
| REACTOME_PHOSPHOLIPID_METABOLISM DN | 201 | 201 | 0.0000044 | 0.0007354 |
| REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION DN | 292 | 289 | 0.0000165 | 0.0024765 |
| REACTOME_FATTY_ACID_METABOLISM DN | 170 | 170 | 0.0000220 | 0.0030370 |
| REACTOME_ION_CHANNEL_TRANSPORT DN | 172 | 172 | 0.0000285 | 0.0036200 |
| REACTOME_SLC_MEDIATED_TRANSMEMBRANE_TRANSPORT DN | 236 | 234 | 0.0000540 | 0.0063318 |
| REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION DN | 296 | 292 | 0.0000575 | 0.0063318 |
| REACTOME_VESICLE_MEDIATED_TRANSPORT DN | 646 | 628 | 0.0000613 | 0.0063318 |
| REACTOME_NEUTROPHIL_DEGRANULATION DN | 463 | 452 | 0.0000803 | 0.0078149 |
| REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION DN | 365 | 358 | 0.0000945 | 0.0086844 |
| REACTOME_MEMBRANE_TRAFFICKING DN | 607 | 590 | 0.0001604 | 0.0139673 |
| REACTOME_DISEASES_OF_METABOLISM DN | 238 | 235 | 0.0002155 | 0.0178186 |
gsig <- rbind(gsig_up,gsig_dn)
gsigsets <- rownames(gsig)107 significant gene sets were identified.
Calc GSA enrichment scores. First calculate the background which is the detected genes with annotations.
detgenes <- unique(unlist(strsplit(dm$UCSC_RefGene_Name,";")))
reactomegenes <- unique(unlist(gs_symbols))
length(reactomegenes)## [1] 11065BG=detgenes[(which(detgenes %in% reactomegenes))]
BGSIZE=length(BG)
FGUP <- unique(unlist(strsplit(subset(dm,logFC > 0 & adj.P.Val < 0.05)$UCSC_RefGene_Name,";")))
FGUP <- FGUP[which(FGUP %in% reactomegenes)]
FGDN <- unique(unlist(strsplit(subset(dm,logFC < 0 & adj.P.Val < 0.05)$UCSC_RefGene_Name,";")))
FGDN <- FGDN[which(FGDN %in% reactomegenes)]
myes <- lapply(1:nrow(gsig), function(i) {
set=rownames(gsig)[i]
set1=sapply(strsplit(set," "),"[[",1)
setg <- gs_symbols[[which(names(gs_symbols)==set1)]]
setg <- setg[which(setg %in% detgenes)]
SETSIZE=length(setg)
NUMUP = (length(intersect(FGUP,setg))/length(FGUP))
NUMDN = (length(intersect(FGDN,setg))/length(FGDN))
NUM=max(NUMUP,NUMDN)
DEN = (SETSIZE/BGSIZE)
ES=NUM/DEN
res=c("numerator"=NUM,"denominator"=DEN,"ES"=ES)
return(res)
})
myes <- data.frame(do.call(rbind,myes))
gsiges <- data.frame(gsig,myes)
gsigesdn <- gsiges[grep(" DN",rownames(gsiges)),]
gsigesdn <- tail(gsigesdn[order(gsigesdn$ES),],10)
gsigesdn <- gsigesdn[nrow(gsigesdn):1,]
gsigesup <- gsiges[grep(" UP",rownames(gsiges)),]
gsigesup <- tail(gsigesup[order(gsigesup$ES),],10)
gsiges <- rbind(gsigesdn,gsigesup)
barnames <- gsub("_"," ",gsub("REACTOME_","",rownames(gsiges)))
cols <- gsub("FALSE","blue",gsub("TRUE","red",grepl(" UP",barnames)))
barnames <- gsub("DN","",gsub(" UP","",barnames))
par(mar = c(5.1, 27.1, 4.1, 2.1))
barplot(abs(gsiges$ES),horiz=TRUE,las=1,names.arg=barnames, cex.names=0.75,
cex.axis=0.85, col=cols, xlab="Enrichment score",main="GSA")
grid()
GSAmeth Downsample
SAMPLESIZES=c(2,3,6,10,16,22,30)
gsres <- lapply(SAMPLESIZES,function(n) {
SEEDS <- seq(100,5000,100)
dsres <- mclapply(SEEDS, function(SEED) {
set.seed(SEED)
mysample <- sample(1:37,n,replace=FALSE)*2
mysample <- c(mysample,(mysample-1))
mysample <- mysample[order(mysample)]
design2 <- design[mysample,]
design2 <- design2[,colSums(design2)>0]
#mval downsample
mval2 <- mval[,mysample]
dm2 <- runlimma(mval2,design2,myann)
if ( is.na(dm2$logFC[1]) ) {
RES=c("TOT"=0,"TP"=0,"FP"=0,"FN"=length(rownames(gsig)) )
} else {
sigup2 <- rownames(subset(dm2,adj.P.Val<0.05 & UCSC_RefGene_Name != "" & logFC>0))
if ( length(sigup2) < 250 ) { sigup2 <- head(rownames(subset(dm2,logFC>0 & UCSC_RefGene_Name != "" )),250) }
sigdn2 <- rownames(subset(dm2,adj.P.Val<0.05 & UCSC_RefGene_Name != "" & logFC<0))
if ( length(sigdn2) < 250 ) { sigdn2 <- head(rownames(subset(dm2,logFC<0 & UCSC_RefGene_Name != "" )),250) }
gsaup2 <- gsameth(sig.cpg=sigup2, all.cpg=rownames(dm2), collection=gs_entrez, array.type="EPIC")
rownames(gsaup2) <- paste(rownames(gsaup2),"UP")
gsadn2 <- gsameth(sig.cpg=sigdn2, all.cpg=rownames(dm2), collection=gs_entrez, array.type="EPIC")
rownames(gsadn2) <- paste(rownames(gsadn2),"DN")
gsig_up2 <- subset(gsaup2,FDR<0.05)
gsig_dn2 <- subset(gsadn2,FDR<0.05)
gsig2 <- rbind(gsig_up2,gsig_dn2)
TOT=nrow(gsig2)
TP=length(which(rownames(gsig2) %in% rownames(gsig)))
FP=length(which(!rownames(gsig2) %in% rownames(gsig)))
FN=length(which(!rownames(gsig) %in% rownames(gsig2)))
RES=c("TOT"=TOT,"TP"=TP,"FP"=FP,"FN"=FN)
}
RES
}, mc.cores=5)
do.call(rbind,dsres)
})
mx <- matrix(rep(0,200),ncol=4)
colnames(mx) <- c("TOT","TP","FP","FN")
# fix empty matrix
gsres <- lapply(gsres,function(x) {
if ( typeof(x) == "character" ) {
mx
} else {
x
}
} )
par(mfrow=c(3,1))
dots <- lapply(gsres,function(x) { x[,"TP"] })
lapply(dots,summary)## [[1]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.00 0.00 0.00 1.14 0.00 45.00
##
## [[2]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.00 0.00 0.00 0.08 0.00 4.00
##
## [[3]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.00 0.00 0.00 2.26 0.75 23.00
##
## [[4]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.00 5.25 13.50 16.10 23.75 58.00
##
## [[5]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 17.00 32.50 41.50 44.40 57.75 77.00
##
## [[6]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 42.00 57.00 65.00 63.96 73.75 82.00
##
## [[7]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 62.00 76.25 80.00 80.20 85.75 94.00boxplot(dots,names=SAMPLESIZES,col="white",ylab="no. true positives",xlab="sample size",
cex=0,main="GSAmeth",ylim=c(0,nrow(gsig)))
beeswarm(dots,add=TRUE,pch=1,cex=0.6)
abline(h=nrow(gsig))
dots <- lapply(gsres,function(x) { x[,"FP"] })
lapply(dots,summary)## [[1]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.0 0.0 0.0 1.9 0.0 53.0
##
## [[2]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.00 0.00 0.00 0.32 0.00 7.00
##
## [[3]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.00 0.00 0.00 1.54 0.00 22.00
##
## [[4]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.00 1.00 5.50 6.72 9.75 32.00
##
## [[5]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 4.00 9.00 12.50 14.48 18.00 35.00
##
## [[6]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 7.0 12.0 20.0 20.9 29.0 40.0
##
## [[7]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 5.00 13.25 18.00 18.76 24.00 41.00boxplot(dots,names=SAMPLESIZES,col="white",ylab="no. false positives",xlab="sample size",cex=0)
beeswarm(dots,add=TRUE,pch=1,cex=0.6)
dots <- lapply(gsres,function(x) { x[,"TP"] })
TPdots <- do.call(rbind,dots)
dots <- lapply(gsres,function(x) { x[,"FP"] })
FPdots <- do.call(rbind,dots)
ratio <- t(FPdots / (TPdots + FPdots))
ratio <- lapply(1:ncol(ratio),function(i) {ratio[,i]})
lapply(ratio,summary)## [[1]]
## Min. 1st Qu. Median Mean 3rd Qu. Max. NA's
## 0.0000 0.3333 0.5408 0.5740 1.0000 1.0000 41
##
## [[2]]
## Min. 1st Qu. Median Mean 3rd Qu. Max. NA's
## 0.6364 1.0000 1.0000 0.9273 1.0000 1.0000 45
##
## [[3]]
## Min. 1st Qu. Median Mean 3rd Qu. Max. NA's
## 0.0000 0.2083 0.3304 0.3717 0.4750 1.0000 36
##
## [[4]]
## Min. 1st Qu. Median Mean 3rd Qu. Max. NA's
## 0.0000 0.1705 0.2806 0.2638 0.3333 0.5882 8
##
## [[5]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.1282 0.1886 0.2313 0.2400 0.2813 0.3929
##
## [[6]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.1077 0.1840 0.2366 0.2358 0.2866 0.3558
##
## [[7]]
## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 0.05952 0.14934 0.18407 0.18393 0.22098 0.33884boxplot(ratio,names=SAMPLESIZES,col="white",ylab="proportion FP",xlab="sample size",cex=0) ; grid()
beeswarm(ratio,add=TRUE,pch=1,cex=0.6)
par(mfrow=c(1,1))PNG output of boxplots.
png(filename="fig4.png",height=150,width=210,units="mm",res=200)
par(mar = c(4.5, 4.1, 2.1, 0.5))
par(mfrow=c(3,2))
dots <- lapply(ssres,function(x) { x[,"TP"] })
boxplot(dots,names=SAMPLESIZES,col="white",ylab="no. consistent",xlab="sample size",
cex=0,main="LAM", ylim=c(0,nrow(lamsig))) ; grid()
beeswarm(dots,add=TRUE,pch=1,cex=0.6)
abline(h=nrow(lamsig))
dots <- lapply(gsres,function(x) { x[,"TP"] })
boxplot(dots,names=SAMPLESIZES,col="white",ylab="no. consistent",xlab="sample size",
cex=0,main="GSA", ylim=c(0,nrow(gsig))) ; grid()
beeswarm(dots,add=TRUE,pch=1,cex=0.6)
abline(h=nrow(gsig))
dots <- lapply(ssres,function(x) { x[,"FP"] })
boxplot(dots,names=SAMPLESIZES,col="white",ylab="no. inconsistent",xlab="sample size",cex=0) ; grid()
beeswarm(dots,add=TRUE,pch=1,cex=0.6)
dots <- lapply(gsres,function(x) { x[,"FP"] })
boxplot(dots,names=SAMPLESIZES,col="white",ylab="no. inconsistent",xlab="sample size",cex=0) ; grid()
beeswarm(dots,add=TRUE,pch=1,cex=0.6)
dots <- lapply(ssres,function(x) { x[,"TP"] })
TPdots <- do.call(rbind,dots)
dots <- lapply(ssres,function(x) { x[,"FP"] })
FPdots <- do.call(rbind,dots)
ratio <- t(FPdots / (TPdots + FPdots))
ratio <- lapply(1:ncol(ratio),function(i) {ratio[,i]})
boxplot(ratio,names=SAMPLESIZES,col="white",ylab="proportion inconsistent",xlab="sample size",cex=0) ; grid()
beeswarm(ratio,add=TRUE,pch=1,cex=0.6)
dots <- lapply(gsres,function(x) { x[,"TP"] })
TPdots <- do.call(rbind,dots)
dots <- lapply(gsres,function(x) { x[,"FP"] })
FPdots <- do.call(rbind,dots)
ratio <- t(FPdots / (TPdots + FPdots))
ratio <- lapply(1:ncol(ratio),function(i) {ratio[,i]})
boxplot(ratio,names=SAMPLESIZES,col="white",ylab="proportion inconsistent",xlab="sample size",cex=0) ; grid()
beeswarm(ratio,add=TRUE,pch=1,cex=0.6)
dev.off()## png
## 2par(mfrow=c(1,1))Overlap
Use Euler diagrams to find the similarity. First, distinguish based on direction.
lamsigsets2up <- lamsigsets2[grep(" UP", lamsigsets2)]
lamsigsets2dn <- lamsigsets2[grep(" DN", lamsigsets2)]
gsigsetsup <- gsigsets[grep(" UP", gsigsets)]
gsigsetsdn <- gsigsets[grep(" DN", gsigsets)]
v1 <- list("LAM up"=lamsigsets2up,"LAM dn"=lamsigsets2dn,
"GSA up"=gsigsetsup, "GSA dn"=gsigsetsdn)
plot(euler(v1),quantities = TRUE)
message("common")## commonintersect(lamsigsets2up, gsigsetsup)## [1] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_PLURIPOTENT_STEM_CELLS UP"
## [2] "REACTOME_GASTRULATION UP"
## [3] "REACTOME_SIGNALING_BY_WNT UP"
## [4] "REACTOME_ELASTIC_FIBRE_FORMATION UP"
## [5] "REACTOME_SIGNALING_BY_FGFR_IN_DISEASE UP"
## [6] "REACTOME_RNA_POLYMERASE_II_TRANSCRIPTION UP"
## [7] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_MECP2 UP"
## [8] "REACTOME_RHOB_GTPASE_CYCLE UP"
## [9] "REACTOME_DISEASES_OF_SIGNAL_TRANSDUCTION_BY_GROWTH_FACTOR_RECEPTORS_AND_SECOND_MESSENGERS UP"
## [10] "REACTOME_SIGNALING_BY_NTRKS UP"
## [11] "REACTOME_RHOC_GTPASE_CYCLE UP"
## [12] "REACTOME_CLASS_B_2_SECRETIN_FAMILY_RECEPTORS UP"
## [13] "REACTOME_EPH_EPHRIN_SIGNALING UP"
## [14] "REACTOME_EPH_EPHRIN_MEDIATED_REPULSION_OF_CELLS UP"
## [15] "REACTOME_CA2_PATHWAY UP"
## [16] "REACTOME_CLATHRIN_MEDIATED_ENDOCYTOSIS UP"
## [17] "REACTOME_SIGNALING_BY_RHO_GTPASES_MIRO_GTPASES_AND_RHOBTB3 UP"
## [18] "REACTOME_MAPK_FAMILY_SIGNALING_CASCADES UP"
## [19] "REACTOME_GLYCOSAMINOGLYCAN_METABOLISM UP"
## [20] "REACTOME_MEMBRANE_TRAFFICKING UP"
## [21] "REACTOME_RHO_GTPASE_CYCLE UP"
## [22] "REACTOME_SIGNALING_BY_RECEPTOR_TYROSINE_KINASES UP"
## [23] "REACTOME_RHOA_GTPASE_CYCLE UP"
## [24] "REACTOME_VESICLE_MEDIATED_TRANSPORT UP"
## [25] "REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION UP"
## [26] "REACTOME_METABOLISM_OF_LIPIDS UP"intersect(lamsigsets2dn, gsigsetsdn)## [1] "REACTOME_OLFACTORY_SIGNALING_PATHWAY DN"
## [2] "REACTOME_SENSORY_PERCEPTION DN"
## [3] "REACTOME_KERATINIZATION DN"
## [4] "REACTOME_INNATE_IMMUNE_SYSTEM DN"message("specific to LAM")## specific to LAMLAMspec <- setdiff(lamsigsets2up, gsigsetsup)
LAMspec## [1] "REACTOME_REGULATION_OF_GENE_EXPRESSION_IN_EARLY_PANCREATIC_PRECURSOR_CELLS UP"
## [2] "REACTOME_FORMATION_OF_LATERAL_PLATE_MESODERM UP"
## [3] "REACTOME_FBXW7_MUTANTS_AND_NOTCH1_IN_CANCER UP"
## [4] "REACTOME_ENDOSOMAL_VACUOLAR_PATHWAY UP"
## [5] "REACTOME_VITAMINS UP"
## [6] "REACTOME_INTERLEUKIN_9_SIGNALING UP"
## [7] "REACTOME_POU5F1_OCT4_SOX2_NANOG_REPRESS_GENES_RELATED_TO_DIFFERENTIATION UP"
## [8] "REACTOME_REGULATION_OF_GENE_EXPRESSION_IN_LATE_STAGE_BRANCHING_MORPHOGENESIS_PANCREATIC_BUD_PRECURSOR_CELLS UP"
## [9] "REACTOME_REGULATION_OF_GENE_EXPRESSION_BY_HYPOXIA_INDUCIBLE_FACTOR UP"
## [10] "REACTOME_ADRENOCEPTORS UP"
## [11] "REACTOME_ERKS_ARE_INACTIVATED UP"
## [12] "REACTOME_BETA_CATENIN_PHOSPHORYLATION_CASCADE UP"
## [13] "REACTOME_PROSTANOID_LIGAND_RECEPTORS UP"
## [14] "REACTOME_ACTIVATION_OF_THE_TFAP2_AP_2_FAMILY_OF_TRANSCRIPTION_FACTORS UP"
## [15] "REACTOME_SIGNALING_BY_CTNNB1_PHOSPHO_SITE_MUTANTS UP"
## [16] "REACTOME_NEGATIVE_REGULATION_OF_ACTIVITY_OF_TFAP2_AP_2_FAMILY_TRANSCRIPTION_FACTORS UP"
## [17] "REACTOME_REGULATION_OF_FOXO_TRANSCRIPTIONAL_ACTIVITY_BY_ACETYLATION UP"
## [18] "REACTOME_SIGNALING_BY_RNF43_MUTANTS UP"
## [19] "REACTOME_RESPONSE_TO_METAL_IONS UP"
## [20] "REACTOME_ACTIVATION_OF_ANTERIOR_HOX_GENES_IN_HINDBRAIN_DEVELOPMENT_DURING_EARLY_EMBRYOGENESIS UP"
## [21] "REACTOME_METALLOTHIONEINS_BIND_METALS UP"
## [22] "REACTOME_VLDLR_INTERNALISATION_AND_DEGRADATION UP"
## [23] "REACTOME_SIRT1_NEGATIVELY_REGULATES_RRNA_EXPRESSION UP"
## [24] "REACTOME_ERCC6_CSB_AND_EHMT2_G9A_POSITIVELY_REGULATE_RRNA_EXPRESSION UP"
## [25] "REACTOME_RUNX3_REGULATES_NOTCH_SIGNALING UP"
## [26] "REACTOME_SUMOYLATION_OF_TRANSCRIPTION_FACTORS UP"
## [27] "REACTOME_DNA_METHYLATION UP"
## [28] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_TESTIS_DIFFERENTIATION UP"
## [29] "REACTOME_YAP1_AND_WWTR1_TAZ_STIMULATED_GENE_EXPRESSION UP"
## [30] "REACTOME_PRC2_METHYLATES_HISTONES_AND_DNA UP"
## [31] "REACTOME_ASSEMBLY_OF_THE_ORC_COMPLEX_AT_THE_ORIGIN_OF_REPLICATION UP"
## [32] "REACTOME_FORMATION_OF_AXIAL_MESODERM UP"
## [33] "REACTOME_ACTIVATED_PKN1_STIMULATES_TRANSCRIPTION_OF_AR_ANDROGEN_RECEPTOR_REGULATED_GENES_KLK2_AND_KLK3 UP"
## [34] "REACTOME_RHO_GTPASES_ACTIVATE_ROCKS UP"
## [35] "REACTOME_SIGNALING_BY_WNT_IN_CANCER UP"
## [36] "REACTOME_FORMATION_OF_THE_BETA_CATENIN_TCF_TRANSACTIVATING_COMPLEX UP"
## [37] "REACTOME_HDACS_DEACETYLATE_HISTONES UP"
## [38] "REACTOME_RUNX1_REGULATES_GENES_INVOLVED_IN_MEGAKARYOCYTE_DIFFERENTIATION_AND_PLATELET_FUNCTION UP"
## [39] "REACTOME_CELL_EXTRACELLULAR_MATRIX_INTERACTIONS UP"
## [40] "REACTOME_B_WICH_COMPLEX_POSITIVELY_REGULATES_RRNA_EXPRESSION UP"
## [41] "REACTOME_FORMATION_OF_PARAXIAL_MESODERM UP"
## [42] "REACTOME_NGF_STIMULATED_TRANSCRIPTION UP"
## [43] "REACTOME_POSITIVE_EPIGENETIC_REGULATION_OF_RRNA_EXPRESSION UP"
## [44] "REACTOME_CONDENSATION_OF_PROPHASE_CHROMOSOMES UP"
## [45] "REACTOME_RMTS_METHYLATE_HISTONE_ARGININES UP"
## [46] "REACTOME_DISASSEMBLY_OF_THE_DESTRUCTION_COMPLEX_AND_RECRUITMENT_OF_AXIN_TO_THE_MEMBRANE UP"
## [47] "REACTOME_INHIBITION_OF_DNA_RECOMBINATION_AT_TELOMERE UP"
## [48] "REACTOME_REGULATION_OF_FZD_BY_UBIQUITINATION UP"
## [49] "REACTOME_MITOCHONDRIAL_IRON_SULFUR_CLUSTER_BIOGENESIS UP"
## [50] "REACTOME_RECOGNITION_AND_ASSOCIATION_OF_DNA_GLYCOSYLASE_WITH_SITE_CONTAINING_AN_AFFECTED_PURINE UP"
## [51] "REACTOME_RHO_GTPASES_ACTIVATE_PKNS UP"
## [52] "REACTOME_DOWNREGULATION_OF_SMAD2_3_SMAD4_TRANSCRIPTIONAL_ACTIVITY UP"
## [53] "REACTOME_HATS_ACETYLATE_HISTONES UP"
## [54] "REACTOME_NUCLEAR_EVENTS_KINASE_AND_TRANSCRIPTION_FACTOR_ACTIVATION UP"
## [55] "REACTOME_SEMA4D_INDUCED_CELL_MIGRATION_AND_GROWTH_CONE_COLLAPSE UP"
## [56] "REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_ADDITIONAL_CELL_CYCLE_GENES_WHOSE_EXACT_ROLE_IN_THE_P53_PATHWAY_REMAIN_UNCERTAIN UP"
## [57] "REACTOME_REGULATION_OF_BETA_CELL_DEVELOPMENT UP"
## [58] "REACTOME_DISEASES_OF_PROGRAMMED_CELL_DEATH UP"
## [59] "REACTOME_METABOLISM_OF_NITRIC_OXIDE_NOS3_ACTIVATION_AND_REGULATION UP"
## [60] "REACTOME_SEMA4D_IN_SEMAPHORIN_SIGNALING UP"
## [61] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_GRANULOPOIESIS UP"
## [62] "REACTOME_RNA_POLYMERASE_I_PROMOTER_ESCAPE UP"
## [63] "REACTOME_NEGATIVE_EPIGENETIC_REGULATION_OF_RRNA_EXPRESSION UP"
## [64] "REACTOME_MEIOTIC_RECOMBINATION UP"
## [65] "REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION UP"
## [66] "REACTOME_BASE_EXCISION_REPAIR_AP_SITE_FORMATION UP"
## [67] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_SMALL_RNAS UP"
## [68] "REACTOME_GERM_LAYER_FORMATION_AT_GASTRULATION UP"
## [69] "REACTOME_DNA_DAMAGE_TELOMERE_STRESS_INDUCED_SENESCENCE UP"
## [70] "REACTOME_NOTCH3_INTRACELLULAR_DOMAIN_REGULATES_TRANSCRIPTION UP"
## [71] "REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC UP"
## [72] "REACTOME_RHO_GTPASES_ACTIVATE_CIT UP"
## [73] "REACTOME_INTERLEUKIN_7_SIGNALING UP"
## [74] "REACTOME_SIGNALING_BY_HIPPO UP"
## [75] "REACTOME_RAF_INDEPENDENT_MAPK1_3_ACTIVATION UP"
## [76] "REACTOME_SENESCENCE_ASSOCIATED_SECRETORY_PHENOTYPE_SASP UP"
## [77] "REACTOME_ONCOGENE_INDUCED_SENESCENCE UP"
## [78] "REACTOME_BUTYRATE_RESPONSE_FACTOR_1_BRF1_BINDS_AND_DESTABILIZES_MRNA UP"
## [79] "REACTOME_MRNA_DECAY_BY_5_TO_3_EXORIBONUCLEASE UP"
## [80] "REACTOME_PKMTS_METHYLATE_HISTONE_LYSINES UP"
## [81] "REACTOME_NEGATIVE_REGULATION_OF_MAPK_PATHWAY UP"
## [82] "REACTOME_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION UP"
## [83] "REACTOME_ERK_MAPK_TARGETS UP"
## [84] "REACTOME_HCMV_LATE_EVENTS UP"
## [85] "REACTOME_SIGNALING_BY_FGFR4 UP"
## [86] "REACTOME_FOXO_MEDIATED_TRANSCRIPTION_OF_CELL_CYCLE_GENES UP"
## [87] "REACTOME_TCF_DEPENDENT_SIGNALING_IN_RESPONSE_TO_WNT UP"
## [88] "REACTOME_MEIOTIC_SYNAPSIS UP"
## [89] "REACTOME_SPRY_REGULATION_OF_FGF_SIGNALING UP"
## [90] "REACTOME_TELOMERE_MAINTENANCE UP"
## [91] "REACTOME_FGFR2_ALTERNATIVE_SPLICING UP"
## [92] "REACTOME_RUNX1_REGULATES_TRANSCRIPTION_OF_GENES_INVOLVED_IN_DIFFERENTIATION_OF_HSCS UP"
## [93] "REACTOME_MEIOSIS UP"
## [94] "REACTOME_NEPHRIN_FAMILY_INTERACTIONS UP"
## [95] "REACTOME_INCRETIN_SYNTHESIS_SECRETION_AND_INACTIVATION UP"
## [96] "REACTOME_ESTROGEN_DEPENDENT_GENE_EXPRESSION UP"
## [97] "REACTOME_SIGNALING_BY_BMP UP"
## [98] "REACTOME_CHROMATIN_MODIFYING_ENZYMES UP"
## [99] "REACTOME_HDMS_DEMETHYLATE_HISTONES UP"
## [100] "REACTOME_OXIDATIVE_STRESS_INDUCED_SENESCENCE UP"
## [101] "REACTOME_DOWNSTREAM_SIGNAL_TRANSDUCTION UP"
## [102] "REACTOME_KSRP_KHSRP_BINDS_AND_DESTABILIZES_MRNA UP"
## [103] "REACTOME_SIGNALING_BY_ALK_IN_CANCER UP"
## [104] "REACTOME_SIGNALING_BY_FGFR2_IIIA_TM UP"
## [105] "REACTOME_DEPOSITION_OF_NEW_CENPA_CONTAINING_NUCLEOSOMES_AT_THE_CENTROMERE UP"
## [106] "REACTOME_PROSTACYCLIN_SIGNALLING_THROUGH_PROSTACYCLIN_RECEPTOR UP"
## [107] "REACTOME_MICRORNA_MIRNA_BIOGENESIS UP"
## [108] "REACTOME_WNT_LIGAND_BIOGENESIS_AND_TRAFFICKING UP"
## [109] "REACTOME_REGULATION_OF_TP53_ACTIVITY_THROUGH_ACETYLATION UP"
## [110] "REACTOME_APOPTOTIC_FACTOR_MEDIATED_RESPONSE UP"
## [111] "REACTOME_SIGNALING_BY_FGFR2 UP"
## [112] "REACTOME_ACTIVATION_OF_SMO UP"
## [113] "REACTOME_DNA_DOUBLE_STRAND_BREAK_RESPONSE UP"
## [114] "REACTOME_BASE_EXCISION_REPAIR UP"
## [115] "REACTOME_NOTCH1_INTRACELLULAR_DOMAIN_REGULATES_TRANSCRIPTION UP"
## [116] "REACTOME_MITOTIC_PROPHASE UP"
## [117] "REACTOME_SIGNALING_BY_FGFR3 UP"
## [118] "REACTOME_PRE_NOTCH_EXPRESSION_AND_PROCESSING UP"
## [119] "REACTOME_NEGATIVE_REGULATION_OF_FGFR4_SIGNALING UP"
## [120] "REACTOME_SIGNALING_BY_NOTCH1_PEST_DOMAIN_MUTANTS_IN_CANCER UP"
## [121] "REACTOME_MAPK_TARGETS_NUCLEAR_EVENTS_MEDIATED_BY_MAP_KINASES UP"
## [122] "REACTOME_SYNTHESIS_SECRETION_AND_INACTIVATION_OF_GLUCAGON_LIKE_PEPTIDE_1_GLP_1 UP"
## [123] "REACTOME_SIGNALING_BY_FGFR2_IN_DISEASE UP"
## [124] "REACTOME_DOWNSTREAM_SIGNALING_OF_ACTIVATED_FGFR4 UP"
## [125] "REACTOME_RAF_ACTIVATION UP"
## [126] "REACTOME_NEGATIVE_REGULATION_OF_FGFR3_SIGNALING UP"
## [127] "REACTOME_TRANSCRIPTIONAL_ACTIVITY_OF_SMAD2_SMAD3_SMAD4_HETEROTRIMER UP"
## [128] "REACTOME_ESR_MEDIATED_SIGNALING UP"
## [129] "REACTOME_DEGRADATION_OF_BETA_CATENIN_BY_THE_DESTRUCTION_COMPLEX UP"
## [130] "REACTOME_CHROMOSOME_MAINTENANCE UP"
## [131] "REACTOME_ABORTIVE_ELONGATION_OF_HIV_1_TRANSCRIPT_IN_THE_ABSENCE_OF_TAT UP"
## [132] "REACTOME_SMAD2_SMAD3_SMAD4_HETEROTRIMER_REGULATES_TRANSCRIPTION UP"
## [133] "REACTOME_DOWNSTREAM_SIGNALING_OF_ACTIVATED_FGFR3 UP"
## [134] "REACTOME_FGFR2_MUTANT_RECEPTOR_ACTIVATION UP"
## [135] "REACTOME_CYCLIN_D_ASSOCIATED_EVENTS_IN_G1 UP"
## [136] "REACTOME_NEGATIVE_REGULATION_OF_FGFR1_SIGNALING UP"
## [137] "REACTOME_DEACTIVATION_OF_THE_BETA_CATENIN_TRANSACTIVATING_COMPLEX UP"
## [138] "REACTOME_REGULATION_OF_TP53_EXPRESSION_AND_DEGRADATION UP"
## [139] "REACTOME_NEGATIVE_REGULATION_OF_FGFR2_SIGNALING UP"
## [140] "REACTOME_RUNX1_INTERACTS_WITH_CO_FACTORS_WHOSE_PRECISE_EFFECT_ON_RUNX1_TARGETS_IS_NOT_KNOWN UP"
## [141] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_RUNX1 UP"
## [142] "REACTOME_DNA_REPLICATION_PRE_INITIATION UP"
## [143] "REACTOME_SIGNALING_BY_NOTCH3 UP"
## [144] "REACTOME_GENE_SILENCING_BY_RNA UP"
## [145] "REACTOME_CELLULAR_SENESCENCE UP"
## [146] "REACTOME_HCMV_EARLY_EVENTS UP"
## [147] "REACTOME_DOWNSTREAM_SIGNALING_OF_ACTIVATED_FGFR2 UP"
## [148] "REACTOME_RNA_POLYMERASE_II_TRANSCRIBES_SNRNA_GENES UP"
## [149] "REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_TERMINATION UP"
## [150] "REACTOME_NONHOMOLOGOUS_END_JOINING_NHEJ UP"
## [151] "REACTOME_SIGNALING_BY_FGFR UP"
## [152] "REACTOME_DNA_REPLICATION UP"
## [153] "REACTOME_SIGNALING_BY_FGFR1 UP"
## [154] "REACTOME_MOLECULES_ASSOCIATED_WITH_ELASTIC_FIBRES UP"
## [155] "REACTOME_HCMV_INFECTION UP"
## [156] "REACTOME_REGULATION_OF_PTEN_GENE_TRANSCRIPTION UP"
## [157] "REACTOME_AMYLOID_FIBER_FORMATION UP"
## [158] "REACTOME_SIGNALING_BY_ALK UP"
## [159] "REACTOME_DEFECTIVE_INTRINSIC_PATHWAY_FOR_APOPTOSIS UP"
## [160] "REACTOME_PROCESSING_OF_DNA_DOUBLE_STRAND_BREAK_ENDS UP"
## [161] "REACTOME_SIGNALING_BY_NOTCH4 UP"
## [162] "REACTOME_SIGNALING_BY_TGFB_FAMILY_MEMBERS UP"
## [163] "REACTOME_DOWNSTREAM_SIGNALING_OF_ACTIVATED_FGFR1 UP"
## [164] "REACTOME_UCH_PROTEINASES UP"
## [165] "REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX UP"
## [166] "REACTOME_PLASMA_LIPOPROTEIN_CLEARANCE UP"
## [167] "REACTOME_SIGNALING_BY_NUCLEAR_RECEPTORS UP"
## [168] "REACTOME_SIGNALING_BY_NOTCH1 UP"
## [169] "REACTOME_CELLULAR_RESPONSE_TO_HYPOXIA UP"
## [170] "REACTOME_REGULATION_OF_RUNX2_EXPRESSION_AND_ACTIVITY UP"
## [171] "REACTOME_REGULATION_OF_RUNX3_EXPRESSION_AND_ACTIVITY UP"
## [172] "REACTOME_HEDGEHOG_ON_STATE UP"
## [173] "REACTOME_SUMOYLATION_OF_TRANSCRIPTION_COFACTORS UP"
## [174] "REACTOME_RNA_POLYMERASE_II_TRANSCRIPTION_TERMINATION UP"
## [175] "REACTOME_FLT3_SIGNALING_IN_DISEASE UP"
## [176] "REACTOME_METALLOPROTEASE_DUBS UP"
## [177] "REACTOME_SIGNALING_BY_NOTCH UP"
## [178] "REACTOME_ASSOCIATION_OF_TRIC_CCT_WITH_TARGET_PROTEINS_DURING_BIOSYNTHESIS UP"
## [179] "REACTOME_TGF_BETA_RECEPTOR_SIGNALING_ACTIVATES_SMADS UP"
## [180] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_RUNX3 UP"
## [181] "REACTOME_THROMBIN_SIGNALLING_THROUGH_PROTEINASE_ACTIVATED_RECEPTORS_PARS UP"
## [182] "REACTOME_RHOV_GTPASE_CYCLE UP"
## [183] "REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21 UP"
## [184] "REACTOME_HOMOLOGY_DIRECTED_REPAIR UP"
## [185] "REACTOME_DNA_DOUBLE_STRAND_BREAK_REPAIR UP"
## [186] "REACTOME_REGULATION_OF_MECP2_EXPRESSION_AND_ACTIVITY UP"
## [187] "REACTOME_SIGNALING_BY_FGFR1_IN_DISEASE UP"
## [188] "REACTOME_COMPLEX_I_BIOGENESIS UP"
## [189] "REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT UP"
## [190] "REACTOME_EXTENSION_OF_TELOMERES UP"
## [191] "REACTOME_TRNA_PROCESSING_IN_THE_NUCLEUS UP"
## [192] "REACTOME_MRNA_SPLICING UP"
## [193] "REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS UP"
## [194] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_RUNX2 UP"
## [195] "REACTOME_DEADENYLATION_DEPENDENT_MRNA_DECAY UP"
## [196] "REACTOME_PERK_REGULATES_GENE_EXPRESSION UP"
## [197] "REACTOME_SUMOYLATION UP"
## [198] "REACTOME_RHO_GTPASES_ACTIVATE_WASPS_AND_WAVES UP"
## [199] "REACTOME_NEGATIVE_REGULATION_OF_NOTCH4_SIGNALING UP"
## [200] "REACTOME_CYTOSOLIC_SENSORS_OF_PATHOGEN_ASSOCIATED_DNA UP"
## [201] "REACTOME_ASYMMETRIC_LOCALIZATION_OF_PCP_PROTEINS UP"
## [202] "REACTOME_REGULATION_OF_MRNA_STABILITY_BY_PROTEINS_THAT_BIND_AU_RICH_ELEMENTS UP"
## [203] "REACTOME_HIV_TRANSCRIPTION_INITIATION UP"
## [204] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION UP"
## [205] "REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA UP"
## [206] "REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION UP"
## [207] "REACTOME_MAPK6_MAPK4_SIGNALING UP"
## [208] "REACTOME_REGULATION_OF_TP53_ACTIVITY UP"
## [209] "REACTOME_DNA_REPAIR UP"
## [210] "REACTOME_E3_UBIQUITIN_LIGASES_UBIQUITINATE_TARGET_PROTEINS UP"
## [211] "REACTOME_HDR_THROUGH_SINGLE_STRAND_ANNEALING_SSA UP"
## [212] "REACTOME_PTEN_REGULATION UP"
## [213] "REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_CELL_CYCLE_GENES UP"
## [214] "REACTOME_REPRODUCTION UP"
## [215] "REACTOME_SIGNALING_BY_RETINOIC_ACID UP"
## [216] "REACTOME_DEFECTIVE_CFTR_CAUSES_CYSTIC_FIBROSIS UP"
## [217] "REACTOME_G2_M_CHECKPOINTS UP"
## [218] "REACTOME_CYCLIN_A_CDK2_ASSOCIATED_EVENTS_AT_S_PHASE_ENTRY UP"
## [219] "REACTOME_COPII_MEDIATED_VESICLE_TRANSPORT UP"
## [220] "REACTOME_RETROGRADE_TRANSPORT_AT_THE_TRANS_GOLGI_NETWORK UP"
## [221] "REACTOME_TRANSPORT_OF_MATURE_TRANSCRIPT_TO_CYTOPLASM UP"
## [222] "REACTOME_SUMOYLATION_OF_DNA_REPLICATION_PROTEINS UP"
## [223] "REACTOME_ORC1_REMOVAL_FROM_CHROMATIN UP"
## [224] "REACTOME_MRNA_SPLICING_MINOR_PATHWAY UP"
## [225] "REACTOME_GOLGI_ASSOCIATED_VESICLE_BIOGENESIS UP"
## [226] "REACTOME_DNA_DAMAGE_BYPASS UP"
## [227] "REACTOME_POTENTIAL_THERAPEUTICS_FOR_SARS UP"
## [228] "REACTOME_DEGRADATION_OF_AXIN UP"
## [229] "REACTOME_PCP_CE_PATHWAY UP"
## [230] "REACTOME_NUCLEOTIDE_EXCISION_REPAIR UP"
## [231] "REACTOME_PROTEIN_UBIQUITINATION UP"
## [232] "REACTOME_STABILIZATION_OF_P53 UP"
## [233] "REACTOME_DEGRADATION_OF_GLI1_BY_THE_PROTEASOME UP"
## [234] "REACTOME_FORMATION_OF_RNA_POL_II_ELONGATION_COMPLEX UP"
## [235] "REACTOME_RESPIRATORY_ELECTRON_TRANSPORT_ATP_SYNTHESIS_BY_CHEMIOSMOTIC_COUPLING_AND_HEAT_PRODUCTION_BY_UNCOUPLING_PROTEINS UP"
## [236] "REACTOME_AUF1_HNRNP_D0_BINDS_AND_DESTABILIZES_MRNA UP"
## [237] "REACTOME_TRNA_PROCESSING UP"
## [238] "REACTOME_G1_S_DNA_DAMAGE_CHECKPOINTS UP"
## [239] "REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR UP"
## [240] "REACTOME_EXTRA_NUCLEAR_ESTROGEN_SIGNALING UP"
## [241] "REACTOME_MITOTIC_G1_PHASE_AND_G1_S_TRANSITION UP"
## [242] "REACTOME_MITOCHONDRIAL_TRANSLATION UP"
## [243] "REACTOME_RNA_POLYMERASE_II_PRE_TRANSCRIPTION_EVENTS UP"
## [244] "REACTOME_SEMAPHORIN_INTERACTIONS UP"
## [245] "REACTOME_RESPIRATORY_ELECTRON_TRANSPORT UP"
## [246] "REACTOME_BETA_CATENIN_INDEPENDENT_WNT_SIGNALING UP"
## [247] "REACTOME_DUAL_INCISION_IN_TC_NER UP"
## [248] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_TP53 UP"
## [249] "REACTOME_THE_CITRIC_ACID_TCA_CYCLE_AND_RESPIRATORY_ELECTRON_TRANSPORT UP"
## [250] "REACTOME_RHO_GTPASE_EFFECTORS UP"
## [251] "REACTOME_COPI_MEDIATED_ANTEROGRADE_TRANSPORT UP"
## [252] "REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_CELL_DEATH_GENES UP"
## [253] "REACTOME_M_PHASE UP"
## [254] "REACTOME_SUMOYLATION_OF_CHROMATIN_ORGANIZATION_PROTEINS UP"
## [255] "REACTOME_MYD88_INDEPENDENT_TLR4_CASCADE UP"
## [256] "REACTOME_CIRCADIAN_CLOCK UP"
## [257] "REACTOME_GLOBAL_GENOME_NUCLEOTIDE_EXCISION_REPAIR_GG_NER UP"
## [258] "REACTOME_TRANSCRIPTION_COUPLED_NUCLEOTIDE_EXCISION_REPAIR_TC_NER UP"
## [259] "REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_DNA_REPAIR_GENES UP"
## [260] "REACTOME_IRE1ALPHA_ACTIVATES_CHAPERONES UP"
## [261] "REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS UP"
## [262] "REACTOME_CELL_CYCLE_MITOTIC UP"
## [263] "REACTOME_UB_SPECIFIC_PROCESSING_PROTEASES UP"
## [264] "REACTOME_CELL_CYCLE_CHECKPOINTS UP"
## [265] "REACTOME_CELLULAR_RESPONSE_TO_HEAT_STRESS UP"
## [266] "REACTOME_TRANS_GOLGI_NETWORK_VESICLE_BUDDING UP"
## [267] "REACTOME_CELL_CYCLE UP"
## [268] "REACTOME_TRANSCRIPTION_OF_THE_HIV_GENOME UP"
## [269] "REACTOME_METABOLISM_OF_RNA UP"
## [270] "REACTOME_REGULATION_OF_TP53_ACTIVITY_THROUGH_PHOSPHORYLATION UP"
## [271] "REACTOME_REGULATION_OF_CHOLESTEROL_BIOSYNTHESIS_BY_SREBP_SREBF UP"
## [272] "REACTOME_REGULATION_OF_RAS_BY_GAPS UP"
## [273] "REACTOME_TOLL_LIKE_RECEPTOR_9_TLR9_CASCADE UP"
## [274] "REACTOME_SUMOYLATION_OF_DNA_DAMAGE_RESPONSE_AND_REPAIR_PROTEINS UP"
## [275] "REACTOME_HEDGEHOG_LIGAND_BIOGENESIS UP"
## [276] "REACTOME_DEUBIQUITINATION UP"
## [277] "REACTOME_INTERLEUKIN_17_SIGNALING UP"
## [278] "REACTOME_ONCOGENIC_MAPK_SIGNALING UP"
## [279] "REACTOME_PYRUVATE_METABOLISM_AND_CITRIC_ACID_TCA_CYCLE UP"
## [280] "REACTOME_PROTEIN_FOLDING UP"
## [281] "REACTOME_REGULATION_OF_PTEN_STABILITY_AND_ACTIVITY UP"
## [282] "REACTOME_HIV_INFECTION UP"
## [283] "REACTOME_MITOCHONDRIAL_PROTEIN_IMPORT UP"
## [284] "REACTOME_SWITCHING_OF_ORIGINS_TO_A_POST_REPLICATIVE_STATE UP"
## [285] "REACTOME_SCF_BETA_TRCP_MEDIATED_DEGRADATION_OF_EMI1 UP"
## [286] "REACTOME_IRON_UPTAKE_AND_TRANSPORT UP"
## [287] "REACTOME_DECTIN_1_MEDIATED_NONCANONICAL_NF_KB_SIGNALING UP"
## [288] "REACTOME_S_PHASE UP"
## [289] "REACTOME_DEGRADATION_OF_DVL UP"
## [290] "REACTOME_APOPTOSIS UP"
## [291] "REACTOME_SYNTHESIS_OF_DNA UP"
## [292] "REACTOME_HIV_LIFE_CYCLE UP"
## [293] "REACTOME_REGULATION_OF_HSF1_MEDIATED_HEAT_SHOCK_RESPONSE UP"
## [294] "REACTOME_ER_TO_GOLGI_ANTEROGRADE_TRANSPORT UP"
## [295] "REACTOME_HDR_THROUGH_HOMOLOGOUS_RECOMBINATION_HRR UP"
## [296] "REACTOME_DOWNSTREAM_SIGNALING_EVENTS_OF_B_CELL_RECEPTOR_BCR UP"
## [297] "REACTOME_CELLULAR_RESPONSES_TO_STIMULI UP"
## [298] "REACTOME_KEAP1_NFE2L2_PATHWAY UP"
## [299] "REACTOME_HOST_INTERACTIONS_OF_HIV_FACTORS UP"
## [300] "REACTOME_FOXO_MEDIATED_TRANSCRIPTION UP"
## [301] "REACTOME_NUCLEAR_EVENTS_MEDIATED_BY_NFE2L2 UP"
## [302] "REACTOME_RHO_GTPASES_ACTIVATE_FORMINS UP"
## [303] "REACTOME_MITOTIC_METAPHASE_AND_ANAPHASE UP"
## [304] "REACTOME_SPHINGOLIPID_METABOLISM UP"
## [305] "REACTOME_FCERI_MEDIATED_NF_KB_ACTIVATION UP"
## [306] "REACTOME_NEDDYLATION UP"
## [307] "REACTOME_SIGNALING_BY_HEDGEHOG UP"
## [308] "REACTOME_MITOTIC_SPINDLE_CHECKPOINT UP"
## [309] "REACTOME_ANTIVIRAL_MECHANISM_BY_IFN_STIMULATED_GENES UP"
## [310] "REACTOME_PROTEIN_LOCALIZATION UP"
## [311] "REACTOME_REGULATION_OF_LIPID_METABOLISM_BY_PPARALPHA UP"
## [312] "REACTOME_INTERLEUKIN_1_SIGNALING UP"
## [313] "REACTOME_PROGRAMMED_CELL_DEATH UP"
## [314] "REACTOME_REGULATION_OF_PLK1_ACTIVITY_AT_G2_M_TRANSITION UP"
## [315] "REACTOME_SIGNALING_BY_ROBO_RECEPTORS UP"
## [316] "REACTOME_SEPARATION_OF_SISTER_CHROMATIDS UP"
## [317] "REACTOME_CARGO_RECOGNITION_FOR_CLATHRIN_MEDIATED_ENDOCYTOSIS UP"
## [318] "REACTOME_MITOCHONDRIAL_BIOGENESIS UP"
## [319] "REACTOME_INTRACELLULAR_SIGNALING_BY_SECOND_MESSENGERS UP"
## [320] "REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION UP"
## [321] "REACTOME_SARS_COV_1_HOST_INTERACTIONS UP"
## [322] "REACTOME_ASPARAGINE_N_LINKED_GLYCOSYLATION UP"
## [323] "REACTOME_HEDGEHOG_OFF_STATE UP"
## [324] "REACTOME_MITOTIC_G2_G2_M_PHASES UP"
## [325] "REACTOME_RESOLUTION_OF_SISTER_CHROMATID_COHESION UP"
## [326] "REACTOME_TRANSLATION UP"
## [327] "REACTOME_AUTOPHAGY UP"
## [328] "REACTOME_TRANSPORT_TO_THE_GOLGI_AND_SUBSEQUENT_MODIFICATION UP"
## [329] "REACTOME_MITOTIC_PROMETAPHASE UP"
## [330] "REACTOME_REGULATION_OF_EXPRESSION_OF_SLITS_AND_ROBOS UP"
## [331] "REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION UP"
## [332] "REACTOME_INTRA_GOLGI_AND_RETROGRADE_GOLGI_TO_ER_TRAFFIC UP"
## [333] "REACTOME_SARS_COV_1_INFECTION UP"
## [334] "REACTOME_RRNA_PROCESSING UP"
## [335] "REACTOME_INFECTIOUS_DISEASE UP"
## [336] "REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION UP"
## [337] "REACTOME_CELLULAR_RESPONSE_TO_CHEMICAL_STRESS UP"
## [338] "REACTOME_NERVOUS_SYSTEM_DEVELOPMENT UP"
## [339] "REACTOME_ORGANELLE_BIOGENESIS_AND_MAINTENANCE UP"
## [340] "REACTOME_SARS_COV_INFECTIONS UP"
## [341] "REACTOME_DEVELOPMENTAL_BIOLOGY UP"
## [342] "REACTOME_METABOLISM_OF_CARBOHYDRATES UP"
## [343] "REACTOME_SIGNALING_BY_INTERLEUKINS UP"
## [344] "REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM UP"LAMspec <- setdiff(lamsigsets2dn, gsigsetsdn)
LAMspec## [1] "REACTOME_BETA_DEFENSINS DN"
## [2] "REACTOME_METAL_SEQUESTRATION_BY_ANTIMICROBIAL_PROTEINS DN"
## [3] "REACTOME_DIGESTION_OF_DIETARY_CARBOHYDRATE DN"
## [4] "REACTOME_CD22_MEDIATED_BCR_REGULATION DN"
## [5] "REACTOME_DEFENSINS DN"
## [6] "REACTOME_MELANIN_BIOSYNTHESIS DN"
## [7] "REACTOME_ANTIMICROBIAL_PEPTIDES DN"
## [8] "REACTOME_AMINO_ACID_CONJUGATION DN"
## [9] "REACTOME_BIOSYNTHESIS_OF_MARESIN_LIKE_SPMS DN"
## [10] "REACTOME_DIGESTION DN"
## [11] "REACTOME_ALPHA_DEFENSINS DN"
## [12] "REACTOME_ATORVASTATIN_ADME DN"
## [13] "REACTOME_CLASS_C_3_METABOTROPIC_GLUTAMATE_PHEROMONE_RECEPTORS DN"
## [14] "REACTOME_DEFECTIVE_GALNT3_CAUSES_HFTC DN"
## [15] "REACTOME_TRANSPORT_OF_ORGANIC_ANIONS DN"
## [16] "REACTOME_DEFECTIVE_C1GALT1C1_CAUSES_TNPS DN"
## [17] "REACTOME_DECTIN_2_FAMILY DN"
## [18] "REACTOME_DIGESTION_AND_ABSORPTION DN"
## [19] "REACTOME_INITIAL_TRIGGERING_OF_COMPLEMENT DN"
## [20] "REACTOME_CREATION_OF_C4_AND_C2_ACTIVATORS DN"
## [21] "REACTOME_TERMINATION_OF_O_GLYCAN_BIOSYNTHESIS DN"
## [22] "REACTOME_ASPIRIN_ADME DN"
## [23] "REACTOME_REGULATION_OF_TLR_BY_ENDOGENOUS_LIGAND DN"
## [24] "REACTOME_SENSORY_PERCEPTION_OF_TASTE DN"
## [25] "REACTOME_REGULATION_OF_IFNA_IFNB_SIGNALING DN"
## [26] "REACTOME_COMPLEMENT_CASCADE DN"
## [27] "REACTOME_ACTIVATION_OF_MATRIX_METALLOPROTEINASES DN"
## [28] "REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE DN"
## [29] "REACTOME_O_LINKED_GLYCOSYLATION_OF_MUCINS DN"
## [30] "REACTOME_IMMUNOREGULATORY_INTERACTIONS_BETWEEN_A_LYMPHOID_AND_A_NON_LYMPHOID_CELL DN"
## [31] "REACTOME_DRUG_ADME DN"
## [32] "REACTOME_VISUAL_PHOTOTRANSDUCTION DN"message("specific to GSA")## specific to GSAGSAspec <- setdiff(gsigsetsup, lamsigsets2up)
GSAspec## [1] "REACTOME_NEURONAL_SYSTEM UP"
## [2] "REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION UP"
## [3] "REACTOME_CDC42_GTPASE_CYCLE UP"
## [4] "REACTOME_SIGNALING_BY_GPCR UP"
## [5] "REACTOME_RAC1_GTPASE_CYCLE UP"
## [6] "REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES UP"
## [7] "REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS UP"
## [8] "REACTOME_POTASSIUM_CHANNELS UP"
## [9] "REACTOME_ECM_PROTEOGLYCANS UP"
## [10] "REACTOME_DEATH_RECEPTOR_SIGNALING UP"
## [11] "REACTOME_INTEGRATION_OF_ENERGY_METABOLISM UP"
## [12] "REACTOME_HEMOSTASIS UP"
## [13] "REACTOME_DEGRADATION_OF_THE_EXTRACELLULAR_MATRIX UP"
## [14] "REACTOME_TRANSPORT_OF_SMALL_MOLECULES UP"
## [15] "REACTOME_CELL_JUNCTION_ORGANIZATION UP"
## [16] "REACTOME_PROTEIN_PROTEIN_INTERACTIONS_AT_SYNAPSES UP"
## [17] "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION UP"
## [18] "REACTOME_OPIOID_SIGNALLING UP"
## [19] "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP"
## [20] "REACTOME_MUSCLE_CONTRACTION UP"
## [21] "REACTOME_COLLAGEN_FORMATION UP"
## [22] "REACTOME_ASSEMBLY_OF_COLLAGEN_FIBRILS_AND_OTHER_MULTIMERIC_STRUCTURES UP"
## [23] "REACTOME_RAC2_GTPASE_CYCLE UP"
## [24] "REACTOME_STIMULI_SENSING_CHANNELS UP"
## [25] "REACTOME_CELL_CELL_COMMUNICATION UP"
## [26] "REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS UP"
## [27] "REACTOME_INTEGRIN_CELL_SURFACE_INTERACTIONS UP"
## [28] "REACTOME_HEPARAN_SULFATE_HEPARIN_HS_GAG_METABOLISM UP"
## [29] "REACTOME_CELL_CELL_JUNCTION_ORGANIZATION UP"
## [30] "REACTOME_PLATELET_HOMEOSTASIS UP"
## [31] "REACTOME_REGULATION_OF_INSULIN_SECRETION UP"
## [32] "REACTOME_TRAFFICKING_OF_AMPA_RECEPTORS UP"
## [33] "REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS UP"
## [34] "REACTOME_THE_ROLE_OF_NEF_IN_HIV_1_REPLICATION_AND_DISEASE_PATHOGENESIS UP"
## [35] "REACTOME_G_ALPHA_12_13_SIGNALLING_EVENTS UP"
## [36] "REACTOME_NEUREXINS_AND_NEUROLIGINS UP"
## [37] "REACTOME_LAMININ_INTERACTIONS UP"
## [38] "REACTOME_RHOQ_GTPASE_CYCLE UP"
## [39] "REACTOME_CARDIAC_CONDUCTION UP"
## [40] "REACTOME_TRANSPORT_OF_INORGANIC_CATIONS_ANIONS_AND_AMINO_ACIDS_OLIGOPEPTIDES UP"
## [41] "REACTOME_GPCR_LIGAND_BINDING UP"
## [42] "REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK UP"
## [43] "REACTOME_FGFR1_MUTANT_RECEPTOR_ACTIVATION UP"
## [44] "REACTOME_ION_CHANNEL_TRANSPORT UP"
## [45] "REACTOME_RET_SIGNALING UP"
## [46] "REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS UP"
## [47] "REACTOME_EFFECTS_OF_PIP2_HYDROLYSIS UP"
## [48] "REACTOME_RAC3_GTPASE_CYCLE UP"
## [49] "REACTOME_NETRIN_1_SIGNALING UP"GSAspec <- setdiff(gsigsetsdn, lamsigsets2dn)
GSAspec## [1] "REACTOME_METABOLISM_OF_LIPIDS DN"
## [2] "REACTOME_TRANSPORT_OF_SMALL_MOLECULES DN"
## [3] "REACTOME_ADAPTIVE_IMMUNE_SYSTEM DN"
## [4] "REACTOME_HEMOSTASIS DN"
## [5] "REACTOME_RHO_GTPASE_CYCLE DN"
## [6] "REACTOME_NEURONAL_SYSTEM DN"
## [7] "REACTOME_PHOSPHOLIPID_METABOLISM DN"
## [8] "REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION DN"
## [9] "REACTOME_FATTY_ACID_METABOLISM DN"
## [10] "REACTOME_ION_CHANNEL_TRANSPORT DN"
## [11] "REACTOME_SLC_MEDIATED_TRANSMEMBRANE_TRANSPORT DN"
## [12] "REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION DN"
## [13] "REACTOME_VESICLE_MEDIATED_TRANSPORT DN"
## [14] "REACTOME_NEUTROPHIL_DEGRANULATION DN"
## [15] "REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION DN"
## [16] "REACTOME_MEMBRANE_TRAFFICKING DN"
## [17] "REACTOME_DISEASES_OF_METABOLISM DN"
## [18] "REACTOME_MITOTIC_METAPHASE_AND_ANAPHASE DN"
## [19] "REACTOME_RAC1_GTPASE_CYCLE DN"
## [20] "REACTOME_ORGANELLE_BIOGENESIS_AND_MAINTENANCE DN"
## [21] "REACTOME_METABOLISM_OF_CARBOHYDRATES DN"
## [22] "REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES DN"
## [23] "REACTOME_GLYCEROPHOSPHOLIPID_BIOSYNTHESIS DN"
## [24] "REACTOME_MITOTIC_PROMETAPHASE DN"
## [25] "REACTOME_CILIUM_ASSEMBLY DN"
## [26] "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION DN"
## [27] "REACTOME_METABOLISM_OF_STEROIDS DN"
## [28] "REACTOME_INTRACELLULAR_SIGNALING_BY_SECOND_MESSENGERS DN"Euler without direction noted.
lamsigsets2## [1] "REACTOME_REGULATION_OF_GENE_EXPRESSION_IN_EARLY_PANCREATIC_PRECURSOR_CELLS UP"
## [2] "REACTOME_FORMATION_OF_LATERAL_PLATE_MESODERM UP"
## [3] "REACTOME_OLFACTORY_SIGNALING_PATHWAY DN"
## [4] "REACTOME_BETA_DEFENSINS DN"
## [5] "REACTOME_METAL_SEQUESTRATION_BY_ANTIMICROBIAL_PROTEINS DN"
## [6] "REACTOME_DIGESTION_OF_DIETARY_CARBOHYDRATE DN"
## [7] "REACTOME_CD22_MEDIATED_BCR_REGULATION DN"
## [8] "REACTOME_DEFENSINS DN"
## [9] "REACTOME_MELANIN_BIOSYNTHESIS DN"
## [10] "REACTOME_ANTIMICROBIAL_PEPTIDES DN"
## [11] "REACTOME_FBXW7_MUTANTS_AND_NOTCH1_IN_CANCER UP"
## [12] "REACTOME_AMINO_ACID_CONJUGATION DN"
## [13] "REACTOME_ENDOSOMAL_VACUOLAR_PATHWAY UP"
## [14] "REACTOME_VITAMINS UP"
## [15] "REACTOME_BIOSYNTHESIS_OF_MARESIN_LIKE_SPMS DN"
## [16] "REACTOME_INTERLEUKIN_9_SIGNALING UP"
## [17] "REACTOME_SENSORY_PERCEPTION DN"
## [18] "REACTOME_POU5F1_OCT4_SOX2_NANOG_REPRESS_GENES_RELATED_TO_DIFFERENTIATION UP"
## [19] "REACTOME_REGULATION_OF_GENE_EXPRESSION_IN_LATE_STAGE_BRANCHING_MORPHOGENESIS_PANCREATIC_BUD_PRECURSOR_CELLS UP"
## [20] "REACTOME_REGULATION_OF_GENE_EXPRESSION_BY_HYPOXIA_INDUCIBLE_FACTOR UP"
## [21] "REACTOME_DIGESTION DN"
## [22] "REACTOME_ADRENOCEPTORS UP"
## [23] "REACTOME_ERKS_ARE_INACTIVATED UP"
## [24] "REACTOME_ALPHA_DEFENSINS DN"
## [25] "REACTOME_BETA_CATENIN_PHOSPHORYLATION_CASCADE UP"
## [26] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_PLURIPOTENT_STEM_CELLS UP"
## [27] "REACTOME_PROSTANOID_LIGAND_RECEPTORS UP"
## [28] "REACTOME_ATORVASTATIN_ADME DN"
## [29] "REACTOME_CLASS_C_3_METABOTROPIC_GLUTAMATE_PHEROMONE_RECEPTORS DN"
## [30] "REACTOME_DEFECTIVE_GALNT3_CAUSES_HFTC DN"
## [31] "REACTOME_ACTIVATION_OF_THE_TFAP2_AP_2_FAMILY_OF_TRANSCRIPTION_FACTORS UP"
## [32] "REACTOME_SIGNALING_BY_CTNNB1_PHOSPHO_SITE_MUTANTS UP"
## [33] "REACTOME_NEGATIVE_REGULATION_OF_ACTIVITY_OF_TFAP2_AP_2_FAMILY_TRANSCRIPTION_FACTORS UP"
## [34] "REACTOME_REGULATION_OF_FOXO_TRANSCRIPTIONAL_ACTIVITY_BY_ACETYLATION UP"
## [35] "REACTOME_SIGNALING_BY_RNF43_MUTANTS UP"
## [36] "REACTOME_RESPONSE_TO_METAL_IONS UP"
## [37] "REACTOME_ACTIVATION_OF_ANTERIOR_HOX_GENES_IN_HINDBRAIN_DEVELOPMENT_DURING_EARLY_EMBRYOGENESIS UP"
## [38] "REACTOME_METALLOTHIONEINS_BIND_METALS UP"
## [39] "REACTOME_VLDLR_INTERNALISATION_AND_DEGRADATION UP"
## [40] "REACTOME_TRANSPORT_OF_ORGANIC_ANIONS DN"
## [41] "REACTOME_SIRT1_NEGATIVELY_REGULATES_RRNA_EXPRESSION UP"
## [42] "REACTOME_ERCC6_CSB_AND_EHMT2_G9A_POSITIVELY_REGULATE_RRNA_EXPRESSION UP"
## [43] "REACTOME_DEFECTIVE_C1GALT1C1_CAUSES_TNPS DN"
## [44] "REACTOME_DECTIN_2_FAMILY DN"
## [45] "REACTOME_RUNX3_REGULATES_NOTCH_SIGNALING UP"
## [46] "REACTOME_SUMOYLATION_OF_TRANSCRIPTION_FACTORS UP"
## [47] "REACTOME_DNA_METHYLATION UP"
## [48] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_TESTIS_DIFFERENTIATION UP"
## [49] "REACTOME_YAP1_AND_WWTR1_TAZ_STIMULATED_GENE_EXPRESSION UP"
## [50] "REACTOME_PRC2_METHYLATES_HISTONES_AND_DNA UP"
## [51] "REACTOME_ASSEMBLY_OF_THE_ORC_COMPLEX_AT_THE_ORIGIN_OF_REPLICATION UP"
## [52] "REACTOME_GASTRULATION UP"
## [53] "REACTOME_FORMATION_OF_AXIAL_MESODERM UP"
## [54] "REACTOME_DIGESTION_AND_ABSORPTION DN"
## [55] "REACTOME_ACTIVATED_PKN1_STIMULATES_TRANSCRIPTION_OF_AR_ANDROGEN_RECEPTOR_REGULATED_GENES_KLK2_AND_KLK3 UP"
## [56] "REACTOME_RHO_GTPASES_ACTIVATE_ROCKS UP"
## [57] "REACTOME_SIGNALING_BY_WNT_IN_CANCER UP"
## [58] "REACTOME_FORMATION_OF_THE_BETA_CATENIN_TCF_TRANSACTIVATING_COMPLEX UP"
## [59] "REACTOME_HDACS_DEACETYLATE_HISTONES UP"
## [60] "REACTOME_RUNX1_REGULATES_GENES_INVOLVED_IN_MEGAKARYOCYTE_DIFFERENTIATION_AND_PLATELET_FUNCTION UP"
## [61] "REACTOME_CELL_EXTRACELLULAR_MATRIX_INTERACTIONS UP"
## [62] "REACTOME_B_WICH_COMPLEX_POSITIVELY_REGULATES_RRNA_EXPRESSION UP"
## [63] "REACTOME_FORMATION_OF_PARAXIAL_MESODERM UP"
## [64] "REACTOME_NGF_STIMULATED_TRANSCRIPTION UP"
## [65] "REACTOME_POSITIVE_EPIGENETIC_REGULATION_OF_RRNA_EXPRESSION UP"
## [66] "REACTOME_CONDENSATION_OF_PROPHASE_CHROMOSOMES UP"
## [67] "REACTOME_RMTS_METHYLATE_HISTONE_ARGININES UP"
## [68] "REACTOME_DISASSEMBLY_OF_THE_DESTRUCTION_COMPLEX_AND_RECRUITMENT_OF_AXIN_TO_THE_MEMBRANE UP"
## [69] "REACTOME_INHIBITION_OF_DNA_RECOMBINATION_AT_TELOMERE UP"
## [70] "REACTOME_REGULATION_OF_FZD_BY_UBIQUITINATION UP"
## [71] "REACTOME_MITOCHONDRIAL_IRON_SULFUR_CLUSTER_BIOGENESIS UP"
## [72] "REACTOME_INITIAL_TRIGGERING_OF_COMPLEMENT DN"
## [73] "REACTOME_RECOGNITION_AND_ASSOCIATION_OF_DNA_GLYCOSYLASE_WITH_SITE_CONTAINING_AN_AFFECTED_PURINE UP"
## [74] "REACTOME_RHO_GTPASES_ACTIVATE_PKNS UP"
## [75] "REACTOME_DOWNREGULATION_OF_SMAD2_3_SMAD4_TRANSCRIPTIONAL_ACTIVITY UP"
## [76] "REACTOME_HATS_ACETYLATE_HISTONES UP"
## [77] "REACTOME_NUCLEAR_EVENTS_KINASE_AND_TRANSCRIPTION_FACTOR_ACTIVATION UP"
## [78] "REACTOME_SEMA4D_INDUCED_CELL_MIGRATION_AND_GROWTH_CONE_COLLAPSE UP"
## [79] "REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_ADDITIONAL_CELL_CYCLE_GENES_WHOSE_EXACT_ROLE_IN_THE_P53_PATHWAY_REMAIN_UNCERTAIN UP"
## [80] "REACTOME_REGULATION_OF_BETA_CELL_DEVELOPMENT UP"
## [81] "REACTOME_DISEASES_OF_PROGRAMMED_CELL_DEATH UP"
## [82] "REACTOME_METABOLISM_OF_NITRIC_OXIDE_NOS3_ACTIVATION_AND_REGULATION UP"
## [83] "REACTOME_SEMA4D_IN_SEMAPHORIN_SIGNALING UP"
## [84] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_GRANULOPOIESIS UP"
## [85] "REACTOME_CREATION_OF_C4_AND_C2_ACTIVATORS DN"
## [86] "REACTOME_RNA_POLYMERASE_I_PROMOTER_ESCAPE UP"
## [87] "REACTOME_NEGATIVE_EPIGENETIC_REGULATION_OF_RRNA_EXPRESSION UP"
## [88] "REACTOME_MEIOTIC_RECOMBINATION UP"
## [89] "REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION UP"
## [90] "REACTOME_BASE_EXCISION_REPAIR_AP_SITE_FORMATION UP"
## [91] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_SMALL_RNAS UP"
## [92] "REACTOME_GERM_LAYER_FORMATION_AT_GASTRULATION UP"
## [93] "REACTOME_DNA_DAMAGE_TELOMERE_STRESS_INDUCED_SENESCENCE UP"
## [94] "REACTOME_NOTCH3_INTRACELLULAR_DOMAIN_REGULATES_TRANSCRIPTION UP"
## [95] "REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC UP"
## [96] "REACTOME_TERMINATION_OF_O_GLYCAN_BIOSYNTHESIS DN"
## [97] "REACTOME_ASPIRIN_ADME DN"
## [98] "REACTOME_KERATINIZATION DN"
## [99] "REACTOME_RHO_GTPASES_ACTIVATE_CIT UP"
## [100] "REACTOME_INTERLEUKIN_7_SIGNALING UP"
## [101] "REACTOME_SIGNALING_BY_HIPPO UP"
## [102] "REACTOME_RAF_INDEPENDENT_MAPK1_3_ACTIVATION UP"
## [103] "REACTOME_SENESCENCE_ASSOCIATED_SECRETORY_PHENOTYPE_SASP UP"
## [104] "REACTOME_ONCOGENE_INDUCED_SENESCENCE UP"
## [105] "REACTOME_BUTYRATE_RESPONSE_FACTOR_1_BRF1_BINDS_AND_DESTABILIZES_MRNA UP"
## [106] "REACTOME_MRNA_DECAY_BY_5_TO_3_EXORIBONUCLEASE UP"
## [107] "REACTOME_PKMTS_METHYLATE_HISTONE_LYSINES UP"
## [108] "REACTOME_NEGATIVE_REGULATION_OF_MAPK_PATHWAY UP"
## [109] "REACTOME_REGULATION_OF_TLR_BY_ENDOGENOUS_LIGAND DN"
## [110] "REACTOME_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION UP"
## [111] "REACTOME_ERK_MAPK_TARGETS UP"
## [112] "REACTOME_HCMV_LATE_EVENTS UP"
## [113] "REACTOME_SIGNALING_BY_FGFR4 UP"
## [114] "REACTOME_SENSORY_PERCEPTION_OF_TASTE DN"
## [115] "REACTOME_FOXO_MEDIATED_TRANSCRIPTION_OF_CELL_CYCLE_GENES UP"
## [116] "REACTOME_TCF_DEPENDENT_SIGNALING_IN_RESPONSE_TO_WNT UP"
## [117] "REACTOME_MEIOTIC_SYNAPSIS UP"
## [118] "REACTOME_SPRY_REGULATION_OF_FGF_SIGNALING UP"
## [119] "REACTOME_TELOMERE_MAINTENANCE UP"
## [120] "REACTOME_FGFR2_ALTERNATIVE_SPLICING UP"
## [121] "REACTOME_RUNX1_REGULATES_TRANSCRIPTION_OF_GENES_INVOLVED_IN_DIFFERENTIATION_OF_HSCS UP"
## [122] "REACTOME_MEIOSIS UP"
## [123] "REACTOME_NEPHRIN_FAMILY_INTERACTIONS UP"
## [124] "REACTOME_INCRETIN_SYNTHESIS_SECRETION_AND_INACTIVATION UP"
## [125] "REACTOME_ESTROGEN_DEPENDENT_GENE_EXPRESSION UP"
## [126] "REACTOME_SIGNALING_BY_BMP UP"
## [127] "REACTOME_CHROMATIN_MODIFYING_ENZYMES UP"
## [128] "REACTOME_HDMS_DEMETHYLATE_HISTONES UP"
## [129] "REACTOME_OXIDATIVE_STRESS_INDUCED_SENESCENCE UP"
## [130] "REACTOME_DOWNSTREAM_SIGNAL_TRANSDUCTION UP"
## [131] "REACTOME_KSRP_KHSRP_BINDS_AND_DESTABILIZES_MRNA UP"
## [132] "REACTOME_SIGNALING_BY_ALK_IN_CANCER UP"
## [133] "REACTOME_SIGNALING_BY_FGFR2_IIIA_TM UP"
## [134] "REACTOME_DEPOSITION_OF_NEW_CENPA_CONTAINING_NUCLEOSOMES_AT_THE_CENTROMERE UP"
## [135] "REACTOME_PROSTACYCLIN_SIGNALLING_THROUGH_PROSTACYCLIN_RECEPTOR UP"
## [136] "REACTOME_MICRORNA_MIRNA_BIOGENESIS UP"
## [137] "REACTOME_WNT_LIGAND_BIOGENESIS_AND_TRAFFICKING UP"
## [138] "REACTOME_REGULATION_OF_TP53_ACTIVITY_THROUGH_ACETYLATION UP"
## [139] "REACTOME_APOPTOTIC_FACTOR_MEDIATED_RESPONSE UP"
## [140] "REACTOME_SIGNALING_BY_FGFR2 UP"
## [141] "REACTOME_ACTIVATION_OF_SMO UP"
## [142] "REACTOME_DNA_DOUBLE_STRAND_BREAK_RESPONSE UP"
## [143] "REACTOME_BASE_EXCISION_REPAIR UP"
## [144] "REACTOME_NOTCH1_INTRACELLULAR_DOMAIN_REGULATES_TRANSCRIPTION UP"
## [145] "REACTOME_MITOTIC_PROPHASE UP"
## [146] "REACTOME_SIGNALING_BY_FGFR3 UP"
## [147] "REACTOME_PRE_NOTCH_EXPRESSION_AND_PROCESSING UP"
## [148] "REACTOME_NEGATIVE_REGULATION_OF_FGFR4_SIGNALING UP"
## [149] "REACTOME_SIGNALING_BY_WNT UP"
## [150] "REACTOME_SIGNALING_BY_NOTCH1_PEST_DOMAIN_MUTANTS_IN_CANCER UP"
## [151] "REACTOME_MAPK_TARGETS_NUCLEAR_EVENTS_MEDIATED_BY_MAP_KINASES UP"
## [152] "REACTOME_SYNTHESIS_SECRETION_AND_INACTIVATION_OF_GLUCAGON_LIKE_PEPTIDE_1_GLP_1 UP"
## [153] "REACTOME_SIGNALING_BY_FGFR2_IN_DISEASE UP"
## [154] "REACTOME_DOWNSTREAM_SIGNALING_OF_ACTIVATED_FGFR4 UP"
## [155] "REACTOME_RAF_ACTIVATION UP"
## [156] "REACTOME_NEGATIVE_REGULATION_OF_FGFR3_SIGNALING UP"
## [157] "REACTOME_TRANSCRIPTIONAL_ACTIVITY_OF_SMAD2_SMAD3_SMAD4_HETEROTRIMER UP"
## [158] "REACTOME_ESR_MEDIATED_SIGNALING UP"
## [159] "REACTOME_DEGRADATION_OF_BETA_CATENIN_BY_THE_DESTRUCTION_COMPLEX UP"
## [160] "REACTOME_CHROMOSOME_MAINTENANCE UP"
## [161] "REACTOME_ABORTIVE_ELONGATION_OF_HIV_1_TRANSCRIPT_IN_THE_ABSENCE_OF_TAT UP"
## [162] "REACTOME_SMAD2_SMAD3_SMAD4_HETEROTRIMER_REGULATES_TRANSCRIPTION UP"
## [163] "REACTOME_DOWNSTREAM_SIGNALING_OF_ACTIVATED_FGFR3 UP"
## [164] "REACTOME_FGFR2_MUTANT_RECEPTOR_ACTIVATION UP"
## [165] "REACTOME_CYCLIN_D_ASSOCIATED_EVENTS_IN_G1 UP"
## [166] "REACTOME_NEGATIVE_REGULATION_OF_FGFR1_SIGNALING UP"
## [167] "REACTOME_DEACTIVATION_OF_THE_BETA_CATENIN_TRANSACTIVATING_COMPLEX UP"
## [168] "REACTOME_REGULATION_OF_TP53_EXPRESSION_AND_DEGRADATION UP"
## [169] "REACTOME_NEGATIVE_REGULATION_OF_FGFR2_SIGNALING UP"
## [170] "REACTOME_RUNX1_INTERACTS_WITH_CO_FACTORS_WHOSE_PRECISE_EFFECT_ON_RUNX1_TARGETS_IS_NOT_KNOWN UP"
## [171] "REACTOME_REGULATION_OF_IFNA_IFNB_SIGNALING DN"
## [172] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_RUNX1 UP"
## [173] "REACTOME_DNA_REPLICATION_PRE_INITIATION UP"
## [174] "REACTOME_ELASTIC_FIBRE_FORMATION UP"
## [175] "REACTOME_SIGNALING_BY_NOTCH3 UP"
## [176] "REACTOME_GENE_SILENCING_BY_RNA UP"
## [177] "REACTOME_CELLULAR_SENESCENCE UP"
## [178] "REACTOME_HCMV_EARLY_EVENTS UP"
## [179] "REACTOME_COMPLEMENT_CASCADE DN"
## [180] "REACTOME_DOWNSTREAM_SIGNALING_OF_ACTIVATED_FGFR2 UP"
## [181] "REACTOME_RNA_POLYMERASE_II_TRANSCRIBES_SNRNA_GENES UP"
## [182] "REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_TERMINATION UP"
## [183] "REACTOME_NONHOMOLOGOUS_END_JOINING_NHEJ UP"
## [184] "REACTOME_SIGNALING_BY_FGFR UP"
## [185] "REACTOME_DNA_REPLICATION UP"
## [186] "REACTOME_SIGNALING_BY_FGFR1 UP"
## [187] "REACTOME_MOLECULES_ASSOCIATED_WITH_ELASTIC_FIBRES UP"
## [188] "REACTOME_HCMV_INFECTION UP"
## [189] "REACTOME_REGULATION_OF_PTEN_GENE_TRANSCRIPTION UP"
## [190] "REACTOME_AMYLOID_FIBER_FORMATION UP"
## [191] "REACTOME_SIGNALING_BY_ALK UP"
## [192] "REACTOME_DEFECTIVE_INTRINSIC_PATHWAY_FOR_APOPTOSIS UP"
## [193] "REACTOME_PROCESSING_OF_DNA_DOUBLE_STRAND_BREAK_ENDS UP"
## [194] "REACTOME_SIGNALING_BY_NOTCH4 UP"
## [195] "REACTOME_SIGNALING_BY_TGFB_FAMILY_MEMBERS UP"
## [196] "REACTOME_DOWNSTREAM_SIGNALING_OF_ACTIVATED_FGFR1 UP"
## [197] "REACTOME_UCH_PROTEINASES UP"
## [198] "REACTOME_SIGNALING_BY_FGFR_IN_DISEASE UP"
## [199] "REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX UP"
## [200] "REACTOME_PLASMA_LIPOPROTEIN_CLEARANCE UP"
## [201] "REACTOME_SIGNALING_BY_NUCLEAR_RECEPTORS UP"
## [202] "REACTOME_SIGNALING_BY_NOTCH1 UP"
## [203] "REACTOME_CELLULAR_RESPONSE_TO_HYPOXIA UP"
## [204] "REACTOME_REGULATION_OF_RUNX2_EXPRESSION_AND_ACTIVITY UP"
## [205] "REACTOME_REGULATION_OF_RUNX3_EXPRESSION_AND_ACTIVITY UP"
## [206] "REACTOME_RNA_POLYMERASE_II_TRANSCRIPTION UP"
## [207] "REACTOME_HEDGEHOG_ON_STATE UP"
## [208] "REACTOME_SUMOYLATION_OF_TRANSCRIPTION_COFACTORS UP"
## [209] "REACTOME_RNA_POLYMERASE_II_TRANSCRIPTION_TERMINATION UP"
## [210] "REACTOME_FLT3_SIGNALING_IN_DISEASE UP"
## [211] "REACTOME_METALLOPROTEASE_DUBS UP"
## [212] "REACTOME_SIGNALING_BY_NOTCH UP"
## [213] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_MECP2 UP"
## [214] "REACTOME_ASSOCIATION_OF_TRIC_CCT_WITH_TARGET_PROTEINS_DURING_BIOSYNTHESIS UP"
## [215] "REACTOME_TGF_BETA_RECEPTOR_SIGNALING_ACTIVATES_SMADS UP"
## [216] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_RUNX3 UP"
## [217] "REACTOME_THROMBIN_SIGNALLING_THROUGH_PROTEINASE_ACTIVATED_RECEPTORS_PARS UP"
## [218] "REACTOME_RHOV_GTPASE_CYCLE UP"
## [219] "REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21 UP"
## [220] "REACTOME_HOMOLOGY_DIRECTED_REPAIR UP"
## [221] "REACTOME_DNA_DOUBLE_STRAND_BREAK_REPAIR UP"
## [222] "REACTOME_REGULATION_OF_MECP2_EXPRESSION_AND_ACTIVITY UP"
## [223] "REACTOME_SIGNALING_BY_FGFR1_IN_DISEASE UP"
## [224] "REACTOME_COMPLEX_I_BIOGENESIS UP"
## [225] "REACTOME_ACTIVATION_OF_MATRIX_METALLOPROTEINASES DN"
## [226] "REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT UP"
## [227] "REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE DN"
## [228] "REACTOME_EXTENSION_OF_TELOMERES UP"
## [229] "REACTOME_TRNA_PROCESSING_IN_THE_NUCLEUS UP"
## [230] "REACTOME_MRNA_SPLICING UP"
## [231] "REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS UP"
## [232] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_RUNX2 UP"
## [233] "REACTOME_DEADENYLATION_DEPENDENT_MRNA_DECAY UP"
## [234] "REACTOME_PERK_REGULATES_GENE_EXPRESSION UP"
## [235] "REACTOME_SUMOYLATION UP"
## [236] "REACTOME_RHO_GTPASES_ACTIVATE_WASPS_AND_WAVES UP"
## [237] "REACTOME_NEGATIVE_REGULATION_OF_NOTCH4_SIGNALING UP"
## [238] "REACTOME_CYTOSOLIC_SENSORS_OF_PATHOGEN_ASSOCIATED_DNA UP"
## [239] "REACTOME_ASYMMETRIC_LOCALIZATION_OF_PCP_PROTEINS UP"
## [240] "REACTOME_REGULATION_OF_MRNA_STABILITY_BY_PROTEINS_THAT_BIND_AU_RICH_ELEMENTS UP"
## [241] "REACTOME_RHOB_GTPASE_CYCLE UP"
## [242] "REACTOME_O_LINKED_GLYCOSYLATION_OF_MUCINS DN"
## [243] "REACTOME_HIV_TRANSCRIPTION_INITIATION UP"
## [244] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION UP"
## [245] "REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA UP"
## [246] "REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION UP"
## [247] "REACTOME_MAPK6_MAPK4_SIGNALING UP"
## [248] "REACTOME_DISEASES_OF_SIGNAL_TRANSDUCTION_BY_GROWTH_FACTOR_RECEPTORS_AND_SECOND_MESSENGERS UP"
## [249] "REACTOME_SIGNALING_BY_NTRKS UP"
## [250] "REACTOME_REGULATION_OF_TP53_ACTIVITY UP"
## [251] "REACTOME_DNA_REPAIR UP"
## [252] "REACTOME_E3_UBIQUITIN_LIGASES_UBIQUITINATE_TARGET_PROTEINS UP"
## [253] "REACTOME_HDR_THROUGH_SINGLE_STRAND_ANNEALING_SSA UP"
## [254] "REACTOME_RHOC_GTPASE_CYCLE UP"
## [255] "REACTOME_CLASS_B_2_SECRETIN_FAMILY_RECEPTORS UP"
## [256] "REACTOME_PTEN_REGULATION UP"
## [257] "REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_CELL_CYCLE_GENES UP"
## [258] "REACTOME_REPRODUCTION UP"
## [259] "REACTOME_SIGNALING_BY_RETINOIC_ACID UP"
## [260] "REACTOME_DEFECTIVE_CFTR_CAUSES_CYSTIC_FIBROSIS UP"
## [261] "REACTOME_G2_M_CHECKPOINTS UP"
## [262] "REACTOME_CYCLIN_A_CDK2_ASSOCIATED_EVENTS_AT_S_PHASE_ENTRY UP"
## [263] "REACTOME_COPII_MEDIATED_VESICLE_TRANSPORT UP"
## [264] "REACTOME_RETROGRADE_TRANSPORT_AT_THE_TRANS_GOLGI_NETWORK UP"
## [265] "REACTOME_TRANSPORT_OF_MATURE_TRANSCRIPT_TO_CYTOPLASM UP"
## [266] "REACTOME_EPH_EPHRIN_SIGNALING UP"
## [267] "REACTOME_SUMOYLATION_OF_DNA_REPLICATION_PROTEINS UP"
## [268] "REACTOME_ORC1_REMOVAL_FROM_CHROMATIN UP"
## [269] "REACTOME_MRNA_SPLICING_MINOR_PATHWAY UP"
## [270] "REACTOME_GOLGI_ASSOCIATED_VESICLE_BIOGENESIS UP"
## [271] "REACTOME_DNA_DAMAGE_BYPASS UP"
## [272] "REACTOME_POTENTIAL_THERAPEUTICS_FOR_SARS UP"
## [273] "REACTOME_DEGRADATION_OF_AXIN UP"
## [274] "REACTOME_PCP_CE_PATHWAY UP"
## [275] "REACTOME_NUCLEOTIDE_EXCISION_REPAIR UP"
## [276] "REACTOME_PROTEIN_UBIQUITINATION UP"
## [277] "REACTOME_STABILIZATION_OF_P53 UP"
## [278] "REACTOME_DEGRADATION_OF_GLI1_BY_THE_PROTEASOME UP"
## [279] "REACTOME_IMMUNOREGULATORY_INTERACTIONS_BETWEEN_A_LYMPHOID_AND_A_NON_LYMPHOID_CELL DN"
## [280] "REACTOME_FORMATION_OF_RNA_POL_II_ELONGATION_COMPLEX UP"
## [281] "REACTOME_RESPIRATORY_ELECTRON_TRANSPORT_ATP_SYNTHESIS_BY_CHEMIOSMOTIC_COUPLING_AND_HEAT_PRODUCTION_BY_UNCOUPLING_PROTEINS UP"
## [282] "REACTOME_AUF1_HNRNP_D0_BINDS_AND_DESTABILIZES_MRNA UP"
## [283] "REACTOME_TRNA_PROCESSING UP"
## [284] "REACTOME_G1_S_DNA_DAMAGE_CHECKPOINTS UP"
## [285] "REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR UP"
## [286] "REACTOME_EXTRA_NUCLEAR_ESTROGEN_SIGNALING UP"
## [287] "REACTOME_MITOTIC_G1_PHASE_AND_G1_S_TRANSITION UP"
## [288] "REACTOME_MITOCHONDRIAL_TRANSLATION UP"
## [289] "REACTOME_RNA_POLYMERASE_II_PRE_TRANSCRIPTION_EVENTS UP"
## [290] "REACTOME_SEMAPHORIN_INTERACTIONS UP"
## [291] "REACTOME_RESPIRATORY_ELECTRON_TRANSPORT UP"
## [292] "REACTOME_BETA_CATENIN_INDEPENDENT_WNT_SIGNALING UP"
## [293] "REACTOME_DUAL_INCISION_IN_TC_NER UP"
## [294] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_TP53 UP"
## [295] "REACTOME_THE_CITRIC_ACID_TCA_CYCLE_AND_RESPIRATORY_ELECTRON_TRANSPORT UP"
## [296] "REACTOME_RHO_GTPASE_EFFECTORS UP"
## [297] "REACTOME_COPI_MEDIATED_ANTEROGRADE_TRANSPORT UP"
## [298] "REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_CELL_DEATH_GENES UP"
## [299] "REACTOME_M_PHASE UP"
## [300] "REACTOME_SUMOYLATION_OF_CHROMATIN_ORGANIZATION_PROTEINS UP"
## [301] "REACTOME_EPH_EPHRIN_MEDIATED_REPULSION_OF_CELLS UP"
## [302] "REACTOME_MYD88_INDEPENDENT_TLR4_CASCADE UP"
## [303] "REACTOME_CIRCADIAN_CLOCK UP"
## [304] "REACTOME_GLOBAL_GENOME_NUCLEOTIDE_EXCISION_REPAIR_GG_NER UP"
## [305] "REACTOME_TRANSCRIPTION_COUPLED_NUCLEOTIDE_EXCISION_REPAIR_TC_NER UP"
## [306] "REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_DNA_REPAIR_GENES UP"
## [307] "REACTOME_IRE1ALPHA_ACTIVATES_CHAPERONES UP"
## [308] "REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS UP"
## [309] "REACTOME_CELL_CYCLE_MITOTIC UP"
## [310] "REACTOME_UB_SPECIFIC_PROCESSING_PROTEASES UP"
## [311] "REACTOME_CA2_PATHWAY UP"
## [312] "REACTOME_CELL_CYCLE_CHECKPOINTS UP"
## [313] "REACTOME_CELLULAR_RESPONSE_TO_HEAT_STRESS UP"
## [314] "REACTOME_DRUG_ADME DN"
## [315] "REACTOME_TRANS_GOLGI_NETWORK_VESICLE_BUDDING UP"
## [316] "REACTOME_CELL_CYCLE UP"
## [317] "REACTOME_TRANSCRIPTION_OF_THE_HIV_GENOME UP"
## [318] "REACTOME_METABOLISM_OF_RNA UP"
## [319] "REACTOME_REGULATION_OF_TP53_ACTIVITY_THROUGH_PHOSPHORYLATION UP"
## [320] "REACTOME_REGULATION_OF_CHOLESTEROL_BIOSYNTHESIS_BY_SREBP_SREBF UP"
## [321] "REACTOME_REGULATION_OF_RAS_BY_GAPS UP"
## [322] "REACTOME_TOLL_LIKE_RECEPTOR_9_TLR9_CASCADE UP"
## [323] "REACTOME_SUMOYLATION_OF_DNA_DAMAGE_RESPONSE_AND_REPAIR_PROTEINS UP"
## [324] "REACTOME_HEDGEHOG_LIGAND_BIOGENESIS UP"
## [325] "REACTOME_DEUBIQUITINATION UP"
## [326] "REACTOME_INTERLEUKIN_17_SIGNALING UP"
## [327] "REACTOME_ONCOGENIC_MAPK_SIGNALING UP"
## [328] "REACTOME_PYRUVATE_METABOLISM_AND_CITRIC_ACID_TCA_CYCLE UP"
## [329] "REACTOME_PROTEIN_FOLDING UP"
## [330] "REACTOME_REGULATION_OF_PTEN_STABILITY_AND_ACTIVITY UP"
## [331] "REACTOME_HIV_INFECTION UP"
## [332] "REACTOME_MITOCHONDRIAL_PROTEIN_IMPORT UP"
## [333] "REACTOME_SWITCHING_OF_ORIGINS_TO_A_POST_REPLICATIVE_STATE UP"
## [334] "REACTOME_SCF_BETA_TRCP_MEDIATED_DEGRADATION_OF_EMI1 UP"
## [335] "REACTOME_IRON_UPTAKE_AND_TRANSPORT UP"
## [336] "REACTOME_DECTIN_1_MEDIATED_NONCANONICAL_NF_KB_SIGNALING UP"
## [337] "REACTOME_S_PHASE UP"
## [338] "REACTOME_DEGRADATION_OF_DVL UP"
## [339] "REACTOME_APOPTOSIS UP"
## [340] "REACTOME_SYNTHESIS_OF_DNA UP"
## [341] "REACTOME_HIV_LIFE_CYCLE UP"
## [342] "REACTOME_REGULATION_OF_HSF1_MEDIATED_HEAT_SHOCK_RESPONSE UP"
## [343] "REACTOME_ER_TO_GOLGI_ANTEROGRADE_TRANSPORT UP"
## [344] "REACTOME_HDR_THROUGH_HOMOLOGOUS_RECOMBINATION_HRR UP"
## [345] "REACTOME_DOWNSTREAM_SIGNALING_EVENTS_OF_B_CELL_RECEPTOR_BCR UP"
## [346] "REACTOME_CLATHRIN_MEDIATED_ENDOCYTOSIS UP"
## [347] "REACTOME_CELLULAR_RESPONSES_TO_STIMULI UP"
## [348] "REACTOME_KEAP1_NFE2L2_PATHWAY UP"
## [349] "REACTOME_SIGNALING_BY_RHO_GTPASES_MIRO_GTPASES_AND_RHOBTB3 UP"
## [350] "REACTOME_HOST_INTERACTIONS_OF_HIV_FACTORS UP"
## [351] "REACTOME_FOXO_MEDIATED_TRANSCRIPTION UP"
## [352] "REACTOME_NUCLEAR_EVENTS_MEDIATED_BY_NFE2L2 UP"
## [353] "REACTOME_MAPK_FAMILY_SIGNALING_CASCADES UP"
## [354] "REACTOME_RHO_GTPASES_ACTIVATE_FORMINS UP"
## [355] "REACTOME_MITOTIC_METAPHASE_AND_ANAPHASE UP"
## [356] "REACTOME_SPHINGOLIPID_METABOLISM UP"
## [357] "REACTOME_FCERI_MEDIATED_NF_KB_ACTIVATION UP"
## [358] "REACTOME_NEDDYLATION UP"
## [359] "REACTOME_SIGNALING_BY_HEDGEHOG UP"
## [360] "REACTOME_MITOTIC_SPINDLE_CHECKPOINT UP"
## [361] "REACTOME_ANTIVIRAL_MECHANISM_BY_IFN_STIMULATED_GENES UP"
## [362] "REACTOME_PROTEIN_LOCALIZATION UP"
## [363] "REACTOME_REGULATION_OF_LIPID_METABOLISM_BY_PPARALPHA UP"
## [364] "REACTOME_INTERLEUKIN_1_SIGNALING UP"
## [365] "REACTOME_PROGRAMMED_CELL_DEATH UP"
## [366] "REACTOME_REGULATION_OF_PLK1_ACTIVITY_AT_G2_M_TRANSITION UP"
## [367] "REACTOME_SIGNALING_BY_ROBO_RECEPTORS UP"
## [368] "REACTOME_VISUAL_PHOTOTRANSDUCTION DN"
## [369] "REACTOME_SEPARATION_OF_SISTER_CHROMATIDS UP"
## [370] "REACTOME_CARGO_RECOGNITION_FOR_CLATHRIN_MEDIATED_ENDOCYTOSIS UP"
## [371] "REACTOME_MITOCHONDRIAL_BIOGENESIS UP"
## [372] "REACTOME_GLYCOSAMINOGLYCAN_METABOLISM UP"
## [373] "REACTOME_INTRACELLULAR_SIGNALING_BY_SECOND_MESSENGERS UP"
## [374] "REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION UP"
## [375] "REACTOME_SARS_COV_1_HOST_INTERACTIONS UP"
## [376] "REACTOME_ASPARAGINE_N_LINKED_GLYCOSYLATION UP"
## [377] "REACTOME_MEMBRANE_TRAFFICKING UP"
## [378] "REACTOME_RHO_GTPASE_CYCLE UP"
## [379] "REACTOME_SIGNALING_BY_RECEPTOR_TYROSINE_KINASES UP"
## [380] "REACTOME_RHOA_GTPASE_CYCLE UP"
## [381] "REACTOME_HEDGEHOG_OFF_STATE UP"
## [382] "REACTOME_MITOTIC_G2_G2_M_PHASES UP"
## [383] "REACTOME_RESOLUTION_OF_SISTER_CHROMATID_COHESION UP"
## [384] "REACTOME_TRANSLATION UP"
## [385] "REACTOME_AUTOPHAGY UP"
## [386] "REACTOME_TRANSPORT_TO_THE_GOLGI_AND_SUBSEQUENT_MODIFICATION UP"
## [387] "REACTOME_MITOTIC_PROMETAPHASE UP"
## [388] "REACTOME_REGULATION_OF_EXPRESSION_OF_SLITS_AND_ROBOS UP"
## [389] "REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION UP"
## [390] "REACTOME_INTRA_GOLGI_AND_RETROGRADE_GOLGI_TO_ER_TRAFFIC UP"
## [391] "REACTOME_SARS_COV_1_INFECTION UP"
## [392] "REACTOME_RRNA_PROCESSING UP"
## [393] "REACTOME_VESICLE_MEDIATED_TRANSPORT UP"
## [394] "REACTOME_INFECTIOUS_DISEASE UP"
## [395] "REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION UP"
## [396] "REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION UP"
## [397] "REACTOME_CELLULAR_RESPONSE_TO_CHEMICAL_STRESS UP"
## [398] "REACTOME_NERVOUS_SYSTEM_DEVELOPMENT UP"
## [399] "REACTOME_ORGANELLE_BIOGENESIS_AND_MAINTENANCE UP"
## [400] "REACTOME_SARS_COV_INFECTIONS UP"
## [401] "REACTOME_DEVELOPMENTAL_BIOLOGY UP"
## [402] "REACTOME_METABOLISM_OF_CARBOHYDRATES UP"
## [403] "REACTOME_SIGNALING_BY_INTERLEUKINS UP"
## [404] "REACTOME_METABOLISM_OF_LIPIDS UP"
## [405] "REACTOME_INNATE_IMMUNE_SYSTEM DN"
## [406] "REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM UP"gsigsets## [1] "REACTOME_NEURONAL_SYSTEM UP"
## [2] "REACTOME_SIGNALING_BY_RECEPTOR_TYROSINE_KINASES UP"
## [3] "REACTOME_RHO_GTPASE_CYCLE UP"
## [4] "REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION UP"
## [5] "REACTOME_CDC42_GTPASE_CYCLE UP"
## [6] "REACTOME_SIGNALING_BY_GPCR UP"
## [7] "REACTOME_RAC1_GTPASE_CYCLE UP"
## [8] "REACTOME_DISEASES_OF_SIGNAL_TRANSDUCTION_BY_GROWTH_FACTOR_RECEPTORS_AND_SECOND_MESSENGERS UP"
## [9] "REACTOME_SIGNALING_BY_RHO_GTPASES_MIRO_GTPASES_AND_RHOBTB3 UP"
## [10] "REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES UP"
## [11] "REACTOME_GLYCOSAMINOGLYCAN_METABOLISM UP"
## [12] "REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS UP"
## [13] "REACTOME_RHOA_GTPASE_CYCLE UP"
## [14] "REACTOME_POTASSIUM_CHANNELS UP"
## [15] "REACTOME_ECM_PROTEOGLYCANS UP"
## [16] "REACTOME_DEATH_RECEPTOR_SIGNALING UP"
## [17] "REACTOME_INTEGRATION_OF_ENERGY_METABOLISM UP"
## [18] "REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION UP"
## [19] "REACTOME_HEMOSTASIS UP"
## [20] "REACTOME_DEGRADATION_OF_THE_EXTRACELLULAR_MATRIX UP"
## [21] "REACTOME_EPH_EPHRIN_SIGNALING UP"
## [22] "REACTOME_TRANSPORT_OF_SMALL_MOLECULES UP"
## [23] "REACTOME_SIGNALING_BY_WNT UP"
## [24] "REACTOME_CELL_JUNCTION_ORGANIZATION UP"
## [25] "REACTOME_PROTEIN_PROTEIN_INTERACTIONS_AT_SYNAPSES UP"
## [26] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_MECP2 UP"
## [27] "REACTOME_VESICLE_MEDIATED_TRANSPORT UP"
## [28] "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION UP"
## [29] "REACTOME_MEMBRANE_TRAFFICKING UP"
## [30] "REACTOME_OPIOID_SIGNALLING UP"
## [31] "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP"
## [32] "REACTOME_MUSCLE_CONTRACTION UP"
## [33] "REACTOME_COLLAGEN_FORMATION UP"
## [34] "REACTOME_RHOC_GTPASE_CYCLE UP"
## [35] "REACTOME_ASSEMBLY_OF_COLLAGEN_FIBRILS_AND_OTHER_MULTIMERIC_STRUCTURES UP"
## [36] "REACTOME_RAC2_GTPASE_CYCLE UP"
## [37] "REACTOME_RNA_POLYMERASE_II_TRANSCRIPTION UP"
## [38] "REACTOME_STIMULI_SENSING_CHANNELS UP"
## [39] "REACTOME_CELL_CELL_COMMUNICATION UP"
## [40] "REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS UP"
## [41] "REACTOME_CA2_PATHWAY UP"
## [42] "REACTOME_INTEGRIN_CELL_SURFACE_INTERACTIONS UP"
## [43] "REACTOME_HEPARAN_SULFATE_HEPARIN_HS_GAG_METABOLISM UP"
## [44] "REACTOME_CELL_CELL_JUNCTION_ORGANIZATION UP"
## [45] "REACTOME_PLATELET_HOMEOSTASIS UP"
## [46] "REACTOME_CLATHRIN_MEDIATED_ENDOCYTOSIS UP"
## [47] "REACTOME_REGULATION_OF_INSULIN_SECRETION UP"
## [48] "REACTOME_TRAFFICKING_OF_AMPA_RECEPTORS UP"
## [49] "REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS UP"
## [50] "REACTOME_THE_ROLE_OF_NEF_IN_HIV_1_REPLICATION_AND_DISEASE_PATHOGENESIS UP"
## [51] "REACTOME_METABOLISM_OF_LIPIDS UP"
## [52] "REACTOME_SIGNALING_BY_NTRKS UP"
## [53] "REACTOME_G_ALPHA_12_13_SIGNALLING_EVENTS UP"
## [54] "REACTOME_SIGNALING_BY_FGFR_IN_DISEASE UP"
## [55] "REACTOME_EPH_EPHRIN_MEDIATED_REPULSION_OF_CELLS UP"
## [56] "REACTOME_NEUREXINS_AND_NEUROLIGINS UP"
## [57] "REACTOME_LAMININ_INTERACTIONS UP"
## [58] "REACTOME_RHOQ_GTPASE_CYCLE UP"
## [59] "REACTOME_CARDIAC_CONDUCTION UP"
## [60] "REACTOME_CLASS_B_2_SECRETIN_FAMILY_RECEPTORS UP"
## [61] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_PLURIPOTENT_STEM_CELLS UP"
## [62] "REACTOME_TRANSPORT_OF_INORGANIC_CATIONS_ANIONS_AND_AMINO_ACIDS_OLIGOPEPTIDES UP"
## [63] "REACTOME_GPCR_LIGAND_BINDING UP"
## [64] "REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK UP"
## [65] "REACTOME_FGFR1_MUTANT_RECEPTOR_ACTIVATION UP"
## [66] "REACTOME_ION_CHANNEL_TRANSPORT UP"
## [67] "REACTOME_RET_SIGNALING UP"
## [68] "REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS UP"
## [69] "REACTOME_GASTRULATION UP"
## [70] "REACTOME_MAPK_FAMILY_SIGNALING_CASCADES UP"
## [71] "REACTOME_EFFECTS_OF_PIP2_HYDROLYSIS UP"
## [72] "REACTOME_RAC3_GTPASE_CYCLE UP"
## [73] "REACTOME_RHOB_GTPASE_CYCLE UP"
## [74] "REACTOME_ELASTIC_FIBRE_FORMATION UP"
## [75] "REACTOME_NETRIN_1_SIGNALING UP"
## [76] "REACTOME_METABOLISM_OF_LIPIDS DN"
## [77] "REACTOME_INNATE_IMMUNE_SYSTEM DN"
## [78] "REACTOME_TRANSPORT_OF_SMALL_MOLECULES DN"
## [79] "REACTOME_ADAPTIVE_IMMUNE_SYSTEM DN"
## [80] "REACTOME_SENSORY_PERCEPTION DN"
## [81] "REACTOME_HEMOSTASIS DN"
## [82] "REACTOME_RHO_GTPASE_CYCLE DN"
## [83] "REACTOME_OLFACTORY_SIGNALING_PATHWAY DN"
## [84] "REACTOME_NEURONAL_SYSTEM DN"
## [85] "REACTOME_PHOSPHOLIPID_METABOLISM DN"
## [86] "REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION DN"
## [87] "REACTOME_FATTY_ACID_METABOLISM DN"
## [88] "REACTOME_ION_CHANNEL_TRANSPORT DN"
## [89] "REACTOME_SLC_MEDIATED_TRANSMEMBRANE_TRANSPORT DN"
## [90] "REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION DN"
## [91] "REACTOME_VESICLE_MEDIATED_TRANSPORT DN"
## [92] "REACTOME_NEUTROPHIL_DEGRANULATION DN"
## [93] "REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION DN"
## [94] "REACTOME_MEMBRANE_TRAFFICKING DN"
## [95] "REACTOME_DISEASES_OF_METABOLISM DN"
## [96] "REACTOME_KERATINIZATION DN"
## [97] "REACTOME_MITOTIC_METAPHASE_AND_ANAPHASE DN"
## [98] "REACTOME_RAC1_GTPASE_CYCLE DN"
## [99] "REACTOME_ORGANELLE_BIOGENESIS_AND_MAINTENANCE DN"
## [100] "REACTOME_METABOLISM_OF_CARBOHYDRATES DN"
## [101] "REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES DN"
## [102] "REACTOME_GLYCEROPHOSPHOLIPID_BIOSYNTHESIS DN"
## [103] "REACTOME_MITOTIC_PROMETAPHASE DN"
## [104] "REACTOME_CILIUM_ASSEMBLY DN"
## [105] "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION DN"
## [106] "REACTOME_METABOLISM_OF_STEROIDS DN"
## [107] "REACTOME_INTRACELLULAR_SIGNALING_BY_SECOND_MESSENGERS DN"v1 <- list("LAM"=lamsigsets2,"GSA"=gsigsets)
plot(euler(v1),quantities = TRUE)
message("common")## commonintersect(lamsigsets2, gsigsets)## [1] "REACTOME_OLFACTORY_SIGNALING_PATHWAY DN"
## [2] "REACTOME_SENSORY_PERCEPTION DN"
## [3] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_PLURIPOTENT_STEM_CELLS UP"
## [4] "REACTOME_GASTRULATION UP"
## [5] "REACTOME_KERATINIZATION DN"
## [6] "REACTOME_SIGNALING_BY_WNT UP"
## [7] "REACTOME_ELASTIC_FIBRE_FORMATION UP"
## [8] "REACTOME_SIGNALING_BY_FGFR_IN_DISEASE UP"
## [9] "REACTOME_RNA_POLYMERASE_II_TRANSCRIPTION UP"
## [10] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_MECP2 UP"
## [11] "REACTOME_RHOB_GTPASE_CYCLE UP"
## [12] "REACTOME_DISEASES_OF_SIGNAL_TRANSDUCTION_BY_GROWTH_FACTOR_RECEPTORS_AND_SECOND_MESSENGERS UP"
## [13] "REACTOME_SIGNALING_BY_NTRKS UP"
## [14] "REACTOME_RHOC_GTPASE_CYCLE UP"
## [15] "REACTOME_CLASS_B_2_SECRETIN_FAMILY_RECEPTORS UP"
## [16] "REACTOME_EPH_EPHRIN_SIGNALING UP"
## [17] "REACTOME_EPH_EPHRIN_MEDIATED_REPULSION_OF_CELLS UP"
## [18] "REACTOME_CA2_PATHWAY UP"
## [19] "REACTOME_CLATHRIN_MEDIATED_ENDOCYTOSIS UP"
## [20] "REACTOME_SIGNALING_BY_RHO_GTPASES_MIRO_GTPASES_AND_RHOBTB3 UP"
## [21] "REACTOME_MAPK_FAMILY_SIGNALING_CASCADES UP"
## [22] "REACTOME_GLYCOSAMINOGLYCAN_METABOLISM UP"
## [23] "REACTOME_MEMBRANE_TRAFFICKING UP"
## [24] "REACTOME_RHO_GTPASE_CYCLE UP"
## [25] "REACTOME_SIGNALING_BY_RECEPTOR_TYROSINE_KINASES UP"
## [26] "REACTOME_RHOA_GTPASE_CYCLE UP"
## [27] "REACTOME_VESICLE_MEDIATED_TRANSPORT UP"
## [28] "REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION UP"
## [29] "REACTOME_METABOLISM_OF_LIPIDS UP"
## [30] "REACTOME_INNATE_IMMUNE_SYSTEM DN"message("specific to LAM")## specific to LAMLAMspec <- setdiff(lamsigsets2, gsigsets)
LAMspec## [1] "REACTOME_REGULATION_OF_GENE_EXPRESSION_IN_EARLY_PANCREATIC_PRECURSOR_CELLS UP"
## [2] "REACTOME_FORMATION_OF_LATERAL_PLATE_MESODERM UP"
## [3] "REACTOME_BETA_DEFENSINS DN"
## [4] "REACTOME_METAL_SEQUESTRATION_BY_ANTIMICROBIAL_PROTEINS DN"
## [5] "REACTOME_DIGESTION_OF_DIETARY_CARBOHYDRATE DN"
## [6] "REACTOME_CD22_MEDIATED_BCR_REGULATION DN"
## [7] "REACTOME_DEFENSINS DN"
## [8] "REACTOME_MELANIN_BIOSYNTHESIS DN"
## [9] "REACTOME_ANTIMICROBIAL_PEPTIDES DN"
## [10] "REACTOME_FBXW7_MUTANTS_AND_NOTCH1_IN_CANCER UP"
## [11] "REACTOME_AMINO_ACID_CONJUGATION DN"
## [12] "REACTOME_ENDOSOMAL_VACUOLAR_PATHWAY UP"
## [13] "REACTOME_VITAMINS UP"
## [14] "REACTOME_BIOSYNTHESIS_OF_MARESIN_LIKE_SPMS DN"
## [15] "REACTOME_INTERLEUKIN_9_SIGNALING UP"
## [16] "REACTOME_POU5F1_OCT4_SOX2_NANOG_REPRESS_GENES_RELATED_TO_DIFFERENTIATION UP"
## [17] "REACTOME_REGULATION_OF_GENE_EXPRESSION_IN_LATE_STAGE_BRANCHING_MORPHOGENESIS_PANCREATIC_BUD_PRECURSOR_CELLS UP"
## [18] "REACTOME_REGULATION_OF_GENE_EXPRESSION_BY_HYPOXIA_INDUCIBLE_FACTOR UP"
## [19] "REACTOME_DIGESTION DN"
## [20] "REACTOME_ADRENOCEPTORS UP"
## [21] "REACTOME_ERKS_ARE_INACTIVATED UP"
## [22] "REACTOME_ALPHA_DEFENSINS DN"
## [23] "REACTOME_BETA_CATENIN_PHOSPHORYLATION_CASCADE UP"
## [24] "REACTOME_PROSTANOID_LIGAND_RECEPTORS UP"
## [25] "REACTOME_ATORVASTATIN_ADME DN"
## [26] "REACTOME_CLASS_C_3_METABOTROPIC_GLUTAMATE_PHEROMONE_RECEPTORS DN"
## [27] "REACTOME_DEFECTIVE_GALNT3_CAUSES_HFTC DN"
## [28] "REACTOME_ACTIVATION_OF_THE_TFAP2_AP_2_FAMILY_OF_TRANSCRIPTION_FACTORS UP"
## [29] "REACTOME_SIGNALING_BY_CTNNB1_PHOSPHO_SITE_MUTANTS UP"
## [30] "REACTOME_NEGATIVE_REGULATION_OF_ACTIVITY_OF_TFAP2_AP_2_FAMILY_TRANSCRIPTION_FACTORS UP"
## [31] "REACTOME_REGULATION_OF_FOXO_TRANSCRIPTIONAL_ACTIVITY_BY_ACETYLATION UP"
## [32] "REACTOME_SIGNALING_BY_RNF43_MUTANTS UP"
## [33] "REACTOME_RESPONSE_TO_METAL_IONS UP"
## [34] "REACTOME_ACTIVATION_OF_ANTERIOR_HOX_GENES_IN_HINDBRAIN_DEVELOPMENT_DURING_EARLY_EMBRYOGENESIS UP"
## [35] "REACTOME_METALLOTHIONEINS_BIND_METALS UP"
## [36] "REACTOME_VLDLR_INTERNALISATION_AND_DEGRADATION UP"
## [37] "REACTOME_TRANSPORT_OF_ORGANIC_ANIONS DN"
## [38] "REACTOME_SIRT1_NEGATIVELY_REGULATES_RRNA_EXPRESSION UP"
## [39] "REACTOME_ERCC6_CSB_AND_EHMT2_G9A_POSITIVELY_REGULATE_RRNA_EXPRESSION UP"
## [40] "REACTOME_DEFECTIVE_C1GALT1C1_CAUSES_TNPS DN"
## [41] "REACTOME_DECTIN_2_FAMILY DN"
## [42] "REACTOME_RUNX3_REGULATES_NOTCH_SIGNALING UP"
## [43] "REACTOME_SUMOYLATION_OF_TRANSCRIPTION_FACTORS UP"
## [44] "REACTOME_DNA_METHYLATION UP"
## [45] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_TESTIS_DIFFERENTIATION UP"
## [46] "REACTOME_YAP1_AND_WWTR1_TAZ_STIMULATED_GENE_EXPRESSION UP"
## [47] "REACTOME_PRC2_METHYLATES_HISTONES_AND_DNA UP"
## [48] "REACTOME_ASSEMBLY_OF_THE_ORC_COMPLEX_AT_THE_ORIGIN_OF_REPLICATION UP"
## [49] "REACTOME_FORMATION_OF_AXIAL_MESODERM UP"
## [50] "REACTOME_DIGESTION_AND_ABSORPTION DN"
## [51] "REACTOME_ACTIVATED_PKN1_STIMULATES_TRANSCRIPTION_OF_AR_ANDROGEN_RECEPTOR_REGULATED_GENES_KLK2_AND_KLK3 UP"
## [52] "REACTOME_RHO_GTPASES_ACTIVATE_ROCKS UP"
## [53] "REACTOME_SIGNALING_BY_WNT_IN_CANCER UP"
## [54] "REACTOME_FORMATION_OF_THE_BETA_CATENIN_TCF_TRANSACTIVATING_COMPLEX UP"
## [55] "REACTOME_HDACS_DEACETYLATE_HISTONES UP"
## [56] "REACTOME_RUNX1_REGULATES_GENES_INVOLVED_IN_MEGAKARYOCYTE_DIFFERENTIATION_AND_PLATELET_FUNCTION UP"
## [57] "REACTOME_CELL_EXTRACELLULAR_MATRIX_INTERACTIONS UP"
## [58] "REACTOME_B_WICH_COMPLEX_POSITIVELY_REGULATES_RRNA_EXPRESSION UP"
## [59] "REACTOME_FORMATION_OF_PARAXIAL_MESODERM UP"
## [60] "REACTOME_NGF_STIMULATED_TRANSCRIPTION UP"
## [61] "REACTOME_POSITIVE_EPIGENETIC_REGULATION_OF_RRNA_EXPRESSION UP"
## [62] "REACTOME_CONDENSATION_OF_PROPHASE_CHROMOSOMES UP"
## [63] "REACTOME_RMTS_METHYLATE_HISTONE_ARGININES UP"
## [64] "REACTOME_DISASSEMBLY_OF_THE_DESTRUCTION_COMPLEX_AND_RECRUITMENT_OF_AXIN_TO_THE_MEMBRANE UP"
## [65] "REACTOME_INHIBITION_OF_DNA_RECOMBINATION_AT_TELOMERE UP"
## [66] "REACTOME_REGULATION_OF_FZD_BY_UBIQUITINATION UP"
## [67] "REACTOME_MITOCHONDRIAL_IRON_SULFUR_CLUSTER_BIOGENESIS UP"
## [68] "REACTOME_INITIAL_TRIGGERING_OF_COMPLEMENT DN"
## [69] "REACTOME_RECOGNITION_AND_ASSOCIATION_OF_DNA_GLYCOSYLASE_WITH_SITE_CONTAINING_AN_AFFECTED_PURINE UP"
## [70] "REACTOME_RHO_GTPASES_ACTIVATE_PKNS UP"
## [71] "REACTOME_DOWNREGULATION_OF_SMAD2_3_SMAD4_TRANSCRIPTIONAL_ACTIVITY UP"
## [72] "REACTOME_HATS_ACETYLATE_HISTONES UP"
## [73] "REACTOME_NUCLEAR_EVENTS_KINASE_AND_TRANSCRIPTION_FACTOR_ACTIVATION UP"
## [74] "REACTOME_SEMA4D_INDUCED_CELL_MIGRATION_AND_GROWTH_CONE_COLLAPSE UP"
## [75] "REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_ADDITIONAL_CELL_CYCLE_GENES_WHOSE_EXACT_ROLE_IN_THE_P53_PATHWAY_REMAIN_UNCERTAIN UP"
## [76] "REACTOME_REGULATION_OF_BETA_CELL_DEVELOPMENT UP"
## [77] "REACTOME_DISEASES_OF_PROGRAMMED_CELL_DEATH UP"
## [78] "REACTOME_METABOLISM_OF_NITRIC_OXIDE_NOS3_ACTIVATION_AND_REGULATION UP"
## [79] "REACTOME_SEMA4D_IN_SEMAPHORIN_SIGNALING UP"
## [80] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_GRANULOPOIESIS UP"
## [81] "REACTOME_CREATION_OF_C4_AND_C2_ACTIVATORS DN"
## [82] "REACTOME_RNA_POLYMERASE_I_PROMOTER_ESCAPE UP"
## [83] "REACTOME_NEGATIVE_EPIGENETIC_REGULATION_OF_RRNA_EXPRESSION UP"
## [84] "REACTOME_MEIOTIC_RECOMBINATION UP"
## [85] "REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION UP"
## [86] "REACTOME_BASE_EXCISION_REPAIR_AP_SITE_FORMATION UP"
## [87] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_SMALL_RNAS UP"
## [88] "REACTOME_GERM_LAYER_FORMATION_AT_GASTRULATION UP"
## [89] "REACTOME_DNA_DAMAGE_TELOMERE_STRESS_INDUCED_SENESCENCE UP"
## [90] "REACTOME_NOTCH3_INTRACELLULAR_DOMAIN_REGULATES_TRANSCRIPTION UP"
## [91] "REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC UP"
## [92] "REACTOME_TERMINATION_OF_O_GLYCAN_BIOSYNTHESIS DN"
## [93] "REACTOME_ASPIRIN_ADME DN"
## [94] "REACTOME_RHO_GTPASES_ACTIVATE_CIT UP"
## [95] "REACTOME_INTERLEUKIN_7_SIGNALING UP"
## [96] "REACTOME_SIGNALING_BY_HIPPO UP"
## [97] "REACTOME_RAF_INDEPENDENT_MAPK1_3_ACTIVATION UP"
## [98] "REACTOME_SENESCENCE_ASSOCIATED_SECRETORY_PHENOTYPE_SASP UP"
## [99] "REACTOME_ONCOGENE_INDUCED_SENESCENCE UP"
## [100] "REACTOME_BUTYRATE_RESPONSE_FACTOR_1_BRF1_BINDS_AND_DESTABILIZES_MRNA UP"
## [101] "REACTOME_MRNA_DECAY_BY_5_TO_3_EXORIBONUCLEASE UP"
## [102] "REACTOME_PKMTS_METHYLATE_HISTONE_LYSINES UP"
## [103] "REACTOME_NEGATIVE_REGULATION_OF_MAPK_PATHWAY UP"
## [104] "REACTOME_REGULATION_OF_TLR_BY_ENDOGENOUS_LIGAND DN"
## [105] "REACTOME_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION UP"
## [106] "REACTOME_ERK_MAPK_TARGETS UP"
## [107] "REACTOME_HCMV_LATE_EVENTS UP"
## [108] "REACTOME_SIGNALING_BY_FGFR4 UP"
## [109] "REACTOME_SENSORY_PERCEPTION_OF_TASTE DN"
## [110] "REACTOME_FOXO_MEDIATED_TRANSCRIPTION_OF_CELL_CYCLE_GENES UP"
## [111] "REACTOME_TCF_DEPENDENT_SIGNALING_IN_RESPONSE_TO_WNT UP"
## [112] "REACTOME_MEIOTIC_SYNAPSIS UP"
## [113] "REACTOME_SPRY_REGULATION_OF_FGF_SIGNALING UP"
## [114] "REACTOME_TELOMERE_MAINTENANCE UP"
## [115] "REACTOME_FGFR2_ALTERNATIVE_SPLICING UP"
## [116] "REACTOME_RUNX1_REGULATES_TRANSCRIPTION_OF_GENES_INVOLVED_IN_DIFFERENTIATION_OF_HSCS UP"
## [117] "REACTOME_MEIOSIS UP"
## [118] "REACTOME_NEPHRIN_FAMILY_INTERACTIONS UP"
## [119] "REACTOME_INCRETIN_SYNTHESIS_SECRETION_AND_INACTIVATION UP"
## [120] "REACTOME_ESTROGEN_DEPENDENT_GENE_EXPRESSION UP"
## [121] "REACTOME_SIGNALING_BY_BMP UP"
## [122] "REACTOME_CHROMATIN_MODIFYING_ENZYMES UP"
## [123] "REACTOME_HDMS_DEMETHYLATE_HISTONES UP"
## [124] "REACTOME_OXIDATIVE_STRESS_INDUCED_SENESCENCE UP"
## [125] "REACTOME_DOWNSTREAM_SIGNAL_TRANSDUCTION UP"
## [126] "REACTOME_KSRP_KHSRP_BINDS_AND_DESTABILIZES_MRNA UP"
## [127] "REACTOME_SIGNALING_BY_ALK_IN_CANCER UP"
## [128] "REACTOME_SIGNALING_BY_FGFR2_IIIA_TM UP"
## [129] "REACTOME_DEPOSITION_OF_NEW_CENPA_CONTAINING_NUCLEOSOMES_AT_THE_CENTROMERE UP"
## [130] "REACTOME_PROSTACYCLIN_SIGNALLING_THROUGH_PROSTACYCLIN_RECEPTOR UP"
## [131] "REACTOME_MICRORNA_MIRNA_BIOGENESIS UP"
## [132] "REACTOME_WNT_LIGAND_BIOGENESIS_AND_TRAFFICKING UP"
## [133] "REACTOME_REGULATION_OF_TP53_ACTIVITY_THROUGH_ACETYLATION UP"
## [134] "REACTOME_APOPTOTIC_FACTOR_MEDIATED_RESPONSE UP"
## [135] "REACTOME_SIGNALING_BY_FGFR2 UP"
## [136] "REACTOME_ACTIVATION_OF_SMO UP"
## [137] "REACTOME_DNA_DOUBLE_STRAND_BREAK_RESPONSE UP"
## [138] "REACTOME_BASE_EXCISION_REPAIR UP"
## [139] "REACTOME_NOTCH1_INTRACELLULAR_DOMAIN_REGULATES_TRANSCRIPTION UP"
## [140] "REACTOME_MITOTIC_PROPHASE UP"
## [141] "REACTOME_SIGNALING_BY_FGFR3 UP"
## [142] "REACTOME_PRE_NOTCH_EXPRESSION_AND_PROCESSING UP"
## [143] "REACTOME_NEGATIVE_REGULATION_OF_FGFR4_SIGNALING UP"
## [144] "REACTOME_SIGNALING_BY_NOTCH1_PEST_DOMAIN_MUTANTS_IN_CANCER UP"
## [145] "REACTOME_MAPK_TARGETS_NUCLEAR_EVENTS_MEDIATED_BY_MAP_KINASES UP"
## [146] "REACTOME_SYNTHESIS_SECRETION_AND_INACTIVATION_OF_GLUCAGON_LIKE_PEPTIDE_1_GLP_1 UP"
## [147] "REACTOME_SIGNALING_BY_FGFR2_IN_DISEASE UP"
## [148] "REACTOME_DOWNSTREAM_SIGNALING_OF_ACTIVATED_FGFR4 UP"
## [149] "REACTOME_RAF_ACTIVATION UP"
## [150] "REACTOME_NEGATIVE_REGULATION_OF_FGFR3_SIGNALING UP"
## [151] "REACTOME_TRANSCRIPTIONAL_ACTIVITY_OF_SMAD2_SMAD3_SMAD4_HETEROTRIMER UP"
## [152] "REACTOME_ESR_MEDIATED_SIGNALING UP"
## [153] "REACTOME_DEGRADATION_OF_BETA_CATENIN_BY_THE_DESTRUCTION_COMPLEX UP"
## [154] "REACTOME_CHROMOSOME_MAINTENANCE UP"
## [155] "REACTOME_ABORTIVE_ELONGATION_OF_HIV_1_TRANSCRIPT_IN_THE_ABSENCE_OF_TAT UP"
## [156] "REACTOME_SMAD2_SMAD3_SMAD4_HETEROTRIMER_REGULATES_TRANSCRIPTION UP"
## [157] "REACTOME_DOWNSTREAM_SIGNALING_OF_ACTIVATED_FGFR3 UP"
## [158] "REACTOME_FGFR2_MUTANT_RECEPTOR_ACTIVATION UP"
## [159] "REACTOME_CYCLIN_D_ASSOCIATED_EVENTS_IN_G1 UP"
## [160] "REACTOME_NEGATIVE_REGULATION_OF_FGFR1_SIGNALING UP"
## [161] "REACTOME_DEACTIVATION_OF_THE_BETA_CATENIN_TRANSACTIVATING_COMPLEX UP"
## [162] "REACTOME_REGULATION_OF_TP53_EXPRESSION_AND_DEGRADATION UP"
## [163] "REACTOME_NEGATIVE_REGULATION_OF_FGFR2_SIGNALING UP"
## [164] "REACTOME_RUNX1_INTERACTS_WITH_CO_FACTORS_WHOSE_PRECISE_EFFECT_ON_RUNX1_TARGETS_IS_NOT_KNOWN UP"
## [165] "REACTOME_REGULATION_OF_IFNA_IFNB_SIGNALING DN"
## [166] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_RUNX1 UP"
## [167] "REACTOME_DNA_REPLICATION_PRE_INITIATION UP"
## [168] "REACTOME_SIGNALING_BY_NOTCH3 UP"
## [169] "REACTOME_GENE_SILENCING_BY_RNA UP"
## [170] "REACTOME_CELLULAR_SENESCENCE UP"
## [171] "REACTOME_HCMV_EARLY_EVENTS UP"
## [172] "REACTOME_COMPLEMENT_CASCADE DN"
## [173] "REACTOME_DOWNSTREAM_SIGNALING_OF_ACTIVATED_FGFR2 UP"
## [174] "REACTOME_RNA_POLYMERASE_II_TRANSCRIBES_SNRNA_GENES UP"
## [175] "REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_TERMINATION UP"
## [176] "REACTOME_NONHOMOLOGOUS_END_JOINING_NHEJ UP"
## [177] "REACTOME_SIGNALING_BY_FGFR UP"
## [178] "REACTOME_DNA_REPLICATION UP"
## [179] "REACTOME_SIGNALING_BY_FGFR1 UP"
## [180] "REACTOME_MOLECULES_ASSOCIATED_WITH_ELASTIC_FIBRES UP"
## [181] "REACTOME_HCMV_INFECTION UP"
## [182] "REACTOME_REGULATION_OF_PTEN_GENE_TRANSCRIPTION UP"
## [183] "REACTOME_AMYLOID_FIBER_FORMATION UP"
## [184] "REACTOME_SIGNALING_BY_ALK UP"
## [185] "REACTOME_DEFECTIVE_INTRINSIC_PATHWAY_FOR_APOPTOSIS UP"
## [186] "REACTOME_PROCESSING_OF_DNA_DOUBLE_STRAND_BREAK_ENDS UP"
## [187] "REACTOME_SIGNALING_BY_NOTCH4 UP"
## [188] "REACTOME_SIGNALING_BY_TGFB_FAMILY_MEMBERS UP"
## [189] "REACTOME_DOWNSTREAM_SIGNALING_OF_ACTIVATED_FGFR1 UP"
## [190] "REACTOME_UCH_PROTEINASES UP"
## [191] "REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX UP"
## [192] "REACTOME_PLASMA_LIPOPROTEIN_CLEARANCE UP"
## [193] "REACTOME_SIGNALING_BY_NUCLEAR_RECEPTORS UP"
## [194] "REACTOME_SIGNALING_BY_NOTCH1 UP"
## [195] "REACTOME_CELLULAR_RESPONSE_TO_HYPOXIA UP"
## [196] "REACTOME_REGULATION_OF_RUNX2_EXPRESSION_AND_ACTIVITY UP"
## [197] "REACTOME_REGULATION_OF_RUNX3_EXPRESSION_AND_ACTIVITY UP"
## [198] "REACTOME_HEDGEHOG_ON_STATE UP"
## [199] "REACTOME_SUMOYLATION_OF_TRANSCRIPTION_COFACTORS UP"
## [200] "REACTOME_RNA_POLYMERASE_II_TRANSCRIPTION_TERMINATION UP"
## [201] "REACTOME_FLT3_SIGNALING_IN_DISEASE UP"
## [202] "REACTOME_METALLOPROTEASE_DUBS UP"
## [203] "REACTOME_SIGNALING_BY_NOTCH UP"
## [204] "REACTOME_ASSOCIATION_OF_TRIC_CCT_WITH_TARGET_PROTEINS_DURING_BIOSYNTHESIS UP"
## [205] "REACTOME_TGF_BETA_RECEPTOR_SIGNALING_ACTIVATES_SMADS UP"
## [206] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_RUNX3 UP"
## [207] "REACTOME_THROMBIN_SIGNALLING_THROUGH_PROTEINASE_ACTIVATED_RECEPTORS_PARS UP"
## [208] "REACTOME_RHOV_GTPASE_CYCLE UP"
## [209] "REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21 UP"
## [210] "REACTOME_HOMOLOGY_DIRECTED_REPAIR UP"
## [211] "REACTOME_DNA_DOUBLE_STRAND_BREAK_REPAIR UP"
## [212] "REACTOME_REGULATION_OF_MECP2_EXPRESSION_AND_ACTIVITY UP"
## [213] "REACTOME_SIGNALING_BY_FGFR1_IN_DISEASE UP"
## [214] "REACTOME_COMPLEX_I_BIOGENESIS UP"
## [215] "REACTOME_ACTIVATION_OF_MATRIX_METALLOPROTEINASES DN"
## [216] "REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT UP"
## [217] "REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE DN"
## [218] "REACTOME_EXTENSION_OF_TELOMERES UP"
## [219] "REACTOME_TRNA_PROCESSING_IN_THE_NUCLEUS UP"
## [220] "REACTOME_MRNA_SPLICING UP"
## [221] "REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS UP"
## [222] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_RUNX2 UP"
## [223] "REACTOME_DEADENYLATION_DEPENDENT_MRNA_DECAY UP"
## [224] "REACTOME_PERK_REGULATES_GENE_EXPRESSION UP"
## [225] "REACTOME_SUMOYLATION UP"
## [226] "REACTOME_RHO_GTPASES_ACTIVATE_WASPS_AND_WAVES UP"
## [227] "REACTOME_NEGATIVE_REGULATION_OF_NOTCH4_SIGNALING UP"
## [228] "REACTOME_CYTOSOLIC_SENSORS_OF_PATHOGEN_ASSOCIATED_DNA UP"
## [229] "REACTOME_ASYMMETRIC_LOCALIZATION_OF_PCP_PROTEINS UP"
## [230] "REACTOME_REGULATION_OF_MRNA_STABILITY_BY_PROTEINS_THAT_BIND_AU_RICH_ELEMENTS UP"
## [231] "REACTOME_O_LINKED_GLYCOSYLATION_OF_MUCINS DN"
## [232] "REACTOME_HIV_TRANSCRIPTION_INITIATION UP"
## [233] "REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION UP"
## [234] "REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA UP"
## [235] "REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION UP"
## [236] "REACTOME_MAPK6_MAPK4_SIGNALING UP"
## [237] "REACTOME_REGULATION_OF_TP53_ACTIVITY UP"
## [238] "REACTOME_DNA_REPAIR UP"
## [239] "REACTOME_E3_UBIQUITIN_LIGASES_UBIQUITINATE_TARGET_PROTEINS UP"
## [240] "REACTOME_HDR_THROUGH_SINGLE_STRAND_ANNEALING_SSA UP"
## [241] "REACTOME_PTEN_REGULATION UP"
## [242] "REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_CELL_CYCLE_GENES UP"
## [243] "REACTOME_REPRODUCTION UP"
## [244] "REACTOME_SIGNALING_BY_RETINOIC_ACID UP"
## [245] "REACTOME_DEFECTIVE_CFTR_CAUSES_CYSTIC_FIBROSIS UP"
## [246] "REACTOME_G2_M_CHECKPOINTS UP"
## [247] "REACTOME_CYCLIN_A_CDK2_ASSOCIATED_EVENTS_AT_S_PHASE_ENTRY UP"
## [248] "REACTOME_COPII_MEDIATED_VESICLE_TRANSPORT UP"
## [249] "REACTOME_RETROGRADE_TRANSPORT_AT_THE_TRANS_GOLGI_NETWORK UP"
## [250] "REACTOME_TRANSPORT_OF_MATURE_TRANSCRIPT_TO_CYTOPLASM UP"
## [251] "REACTOME_SUMOYLATION_OF_DNA_REPLICATION_PROTEINS UP"
## [252] "REACTOME_ORC1_REMOVAL_FROM_CHROMATIN UP"
## [253] "REACTOME_MRNA_SPLICING_MINOR_PATHWAY UP"
## [254] "REACTOME_GOLGI_ASSOCIATED_VESICLE_BIOGENESIS UP"
## [255] "REACTOME_DNA_DAMAGE_BYPASS UP"
## [256] "REACTOME_POTENTIAL_THERAPEUTICS_FOR_SARS UP"
## [257] "REACTOME_DEGRADATION_OF_AXIN UP"
## [258] "REACTOME_PCP_CE_PATHWAY UP"
## [259] "REACTOME_NUCLEOTIDE_EXCISION_REPAIR UP"
## [260] "REACTOME_PROTEIN_UBIQUITINATION UP"
## [261] "REACTOME_STABILIZATION_OF_P53 UP"
## [262] "REACTOME_DEGRADATION_OF_GLI1_BY_THE_PROTEASOME UP"
## [263] "REACTOME_IMMUNOREGULATORY_INTERACTIONS_BETWEEN_A_LYMPHOID_AND_A_NON_LYMPHOID_CELL DN"
## [264] "REACTOME_FORMATION_OF_RNA_POL_II_ELONGATION_COMPLEX UP"
## [265] "REACTOME_RESPIRATORY_ELECTRON_TRANSPORT_ATP_SYNTHESIS_BY_CHEMIOSMOTIC_COUPLING_AND_HEAT_PRODUCTION_BY_UNCOUPLING_PROTEINS UP"
## [266] "REACTOME_AUF1_HNRNP_D0_BINDS_AND_DESTABILIZES_MRNA UP"
## [267] "REACTOME_TRNA_PROCESSING UP"
## [268] "REACTOME_G1_S_DNA_DAMAGE_CHECKPOINTS UP"
## [269] "REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR UP"
## [270] "REACTOME_EXTRA_NUCLEAR_ESTROGEN_SIGNALING UP"
## [271] "REACTOME_MITOTIC_G1_PHASE_AND_G1_S_TRANSITION UP"
## [272] "REACTOME_MITOCHONDRIAL_TRANSLATION UP"
## [273] "REACTOME_RNA_POLYMERASE_II_PRE_TRANSCRIPTION_EVENTS UP"
## [274] "REACTOME_SEMAPHORIN_INTERACTIONS UP"
## [275] "REACTOME_RESPIRATORY_ELECTRON_TRANSPORT UP"
## [276] "REACTOME_BETA_CATENIN_INDEPENDENT_WNT_SIGNALING UP"
## [277] "REACTOME_DUAL_INCISION_IN_TC_NER UP"
## [278] "REACTOME_TRANSCRIPTIONAL_REGULATION_BY_TP53 UP"
## [279] "REACTOME_THE_CITRIC_ACID_TCA_CYCLE_AND_RESPIRATORY_ELECTRON_TRANSPORT UP"
## [280] "REACTOME_RHO_GTPASE_EFFECTORS UP"
## [281] "REACTOME_COPI_MEDIATED_ANTEROGRADE_TRANSPORT UP"
## [282] "REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_CELL_DEATH_GENES UP"
## [283] "REACTOME_M_PHASE UP"
## [284] "REACTOME_SUMOYLATION_OF_CHROMATIN_ORGANIZATION_PROTEINS UP"
## [285] "REACTOME_MYD88_INDEPENDENT_TLR4_CASCADE UP"
## [286] "REACTOME_CIRCADIAN_CLOCK UP"
## [287] "REACTOME_GLOBAL_GENOME_NUCLEOTIDE_EXCISION_REPAIR_GG_NER UP"
## [288] "REACTOME_TRANSCRIPTION_COUPLED_NUCLEOTIDE_EXCISION_REPAIR_TC_NER UP"
## [289] "REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_DNA_REPAIR_GENES UP"
## [290] "REACTOME_IRE1ALPHA_ACTIVATES_CHAPERONES UP"
## [291] "REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS UP"
## [292] "REACTOME_CELL_CYCLE_MITOTIC UP"
## [293] "REACTOME_UB_SPECIFIC_PROCESSING_PROTEASES UP"
## [294] "REACTOME_CELL_CYCLE_CHECKPOINTS UP"
## [295] "REACTOME_CELLULAR_RESPONSE_TO_HEAT_STRESS UP"
## [296] "REACTOME_DRUG_ADME DN"
## [297] "REACTOME_TRANS_GOLGI_NETWORK_VESICLE_BUDDING UP"
## [298] "REACTOME_CELL_CYCLE UP"
## [299] "REACTOME_TRANSCRIPTION_OF_THE_HIV_GENOME UP"
## [300] "REACTOME_METABOLISM_OF_RNA UP"
## [301] "REACTOME_REGULATION_OF_TP53_ACTIVITY_THROUGH_PHOSPHORYLATION UP"
## [302] "REACTOME_REGULATION_OF_CHOLESTEROL_BIOSYNTHESIS_BY_SREBP_SREBF UP"
## [303] "REACTOME_REGULATION_OF_RAS_BY_GAPS UP"
## [304] "REACTOME_TOLL_LIKE_RECEPTOR_9_TLR9_CASCADE UP"
## [305] "REACTOME_SUMOYLATION_OF_DNA_DAMAGE_RESPONSE_AND_REPAIR_PROTEINS UP"
## [306] "REACTOME_HEDGEHOG_LIGAND_BIOGENESIS UP"
## [307] "REACTOME_DEUBIQUITINATION UP"
## [308] "REACTOME_INTERLEUKIN_17_SIGNALING UP"
## [309] "REACTOME_ONCOGENIC_MAPK_SIGNALING UP"
## [310] "REACTOME_PYRUVATE_METABOLISM_AND_CITRIC_ACID_TCA_CYCLE UP"
## [311] "REACTOME_PROTEIN_FOLDING UP"
## [312] "REACTOME_REGULATION_OF_PTEN_STABILITY_AND_ACTIVITY UP"
## [313] "REACTOME_HIV_INFECTION UP"
## [314] "REACTOME_MITOCHONDRIAL_PROTEIN_IMPORT UP"
## [315] "REACTOME_SWITCHING_OF_ORIGINS_TO_A_POST_REPLICATIVE_STATE UP"
## [316] "REACTOME_SCF_BETA_TRCP_MEDIATED_DEGRADATION_OF_EMI1 UP"
## [317] "REACTOME_IRON_UPTAKE_AND_TRANSPORT UP"
## [318] "REACTOME_DECTIN_1_MEDIATED_NONCANONICAL_NF_KB_SIGNALING UP"
## [319] "REACTOME_S_PHASE UP"
## [320] "REACTOME_DEGRADATION_OF_DVL UP"
## [321] "REACTOME_APOPTOSIS UP"
## [322] "REACTOME_SYNTHESIS_OF_DNA UP"
## [323] "REACTOME_HIV_LIFE_CYCLE UP"
## [324] "REACTOME_REGULATION_OF_HSF1_MEDIATED_HEAT_SHOCK_RESPONSE UP"
## [325] "REACTOME_ER_TO_GOLGI_ANTEROGRADE_TRANSPORT UP"
## [326] "REACTOME_HDR_THROUGH_HOMOLOGOUS_RECOMBINATION_HRR UP"
## [327] "REACTOME_DOWNSTREAM_SIGNALING_EVENTS_OF_B_CELL_RECEPTOR_BCR UP"
## [328] "REACTOME_CELLULAR_RESPONSES_TO_STIMULI UP"
## [329] "REACTOME_KEAP1_NFE2L2_PATHWAY UP"
## [330] "REACTOME_HOST_INTERACTIONS_OF_HIV_FACTORS UP"
## [331] "REACTOME_FOXO_MEDIATED_TRANSCRIPTION UP"
## [332] "REACTOME_NUCLEAR_EVENTS_MEDIATED_BY_NFE2L2 UP"
## [333] "REACTOME_RHO_GTPASES_ACTIVATE_FORMINS UP"
## [334] "REACTOME_MITOTIC_METAPHASE_AND_ANAPHASE UP"
## [335] "REACTOME_SPHINGOLIPID_METABOLISM UP"
## [336] "REACTOME_FCERI_MEDIATED_NF_KB_ACTIVATION UP"
## [337] "REACTOME_NEDDYLATION UP"
## [338] "REACTOME_SIGNALING_BY_HEDGEHOG UP"
## [339] "REACTOME_MITOTIC_SPINDLE_CHECKPOINT UP"
## [340] "REACTOME_ANTIVIRAL_MECHANISM_BY_IFN_STIMULATED_GENES UP"
## [341] "REACTOME_PROTEIN_LOCALIZATION UP"
## [342] "REACTOME_REGULATION_OF_LIPID_METABOLISM_BY_PPARALPHA UP"
## [343] "REACTOME_INTERLEUKIN_1_SIGNALING UP"
## [344] "REACTOME_PROGRAMMED_CELL_DEATH UP"
## [345] "REACTOME_REGULATION_OF_PLK1_ACTIVITY_AT_G2_M_TRANSITION UP"
## [346] "REACTOME_SIGNALING_BY_ROBO_RECEPTORS UP"
## [347] "REACTOME_VISUAL_PHOTOTRANSDUCTION DN"
## [348] "REACTOME_SEPARATION_OF_SISTER_CHROMATIDS UP"
## [349] "REACTOME_CARGO_RECOGNITION_FOR_CLATHRIN_MEDIATED_ENDOCYTOSIS UP"
## [350] "REACTOME_MITOCHONDRIAL_BIOGENESIS UP"
## [351] "REACTOME_INTRACELLULAR_SIGNALING_BY_SECOND_MESSENGERS UP"
## [352] "REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION UP"
## [353] "REACTOME_SARS_COV_1_HOST_INTERACTIONS UP"
## [354] "REACTOME_ASPARAGINE_N_LINKED_GLYCOSYLATION UP"
## [355] "REACTOME_HEDGEHOG_OFF_STATE UP"
## [356] "REACTOME_MITOTIC_G2_G2_M_PHASES UP"
## [357] "REACTOME_RESOLUTION_OF_SISTER_CHROMATID_COHESION UP"
## [358] "REACTOME_TRANSLATION UP"
## [359] "REACTOME_AUTOPHAGY UP"
## [360] "REACTOME_TRANSPORT_TO_THE_GOLGI_AND_SUBSEQUENT_MODIFICATION UP"
## [361] "REACTOME_MITOTIC_PROMETAPHASE UP"
## [362] "REACTOME_REGULATION_OF_EXPRESSION_OF_SLITS_AND_ROBOS UP"
## [363] "REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION UP"
## [364] "REACTOME_INTRA_GOLGI_AND_RETROGRADE_GOLGI_TO_ER_TRAFFIC UP"
## [365] "REACTOME_SARS_COV_1_INFECTION UP"
## [366] "REACTOME_RRNA_PROCESSING UP"
## [367] "REACTOME_INFECTIOUS_DISEASE UP"
## [368] "REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION UP"
## [369] "REACTOME_CELLULAR_RESPONSE_TO_CHEMICAL_STRESS UP"
## [370] "REACTOME_NERVOUS_SYSTEM_DEVELOPMENT UP"
## [371] "REACTOME_ORGANELLE_BIOGENESIS_AND_MAINTENANCE UP"
## [372] "REACTOME_SARS_COV_INFECTIONS UP"
## [373] "REACTOME_DEVELOPMENTAL_BIOLOGY UP"
## [374] "REACTOME_METABOLISM_OF_CARBOHYDRATES UP"
## [375] "REACTOME_SIGNALING_BY_INTERLEUKINS UP"
## [376] "REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM UP"message("specific to GSA")## specific to GSAGSAspec <- setdiff(gsigsets, lamsigsets2)
GSAspec## [1] "REACTOME_NEURONAL_SYSTEM UP"
## [2] "REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION UP"
## [3] "REACTOME_CDC42_GTPASE_CYCLE UP"
## [4] "REACTOME_SIGNALING_BY_GPCR UP"
## [5] "REACTOME_RAC1_GTPASE_CYCLE UP"
## [6] "REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES UP"
## [7] "REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS UP"
## [8] "REACTOME_POTASSIUM_CHANNELS UP"
## [9] "REACTOME_ECM_PROTEOGLYCANS UP"
## [10] "REACTOME_DEATH_RECEPTOR_SIGNALING UP"
## [11] "REACTOME_INTEGRATION_OF_ENERGY_METABOLISM UP"
## [12] "REACTOME_HEMOSTASIS UP"
## [13] "REACTOME_DEGRADATION_OF_THE_EXTRACELLULAR_MATRIX UP"
## [14] "REACTOME_TRANSPORT_OF_SMALL_MOLECULES UP"
## [15] "REACTOME_CELL_JUNCTION_ORGANIZATION UP"
## [16] "REACTOME_PROTEIN_PROTEIN_INTERACTIONS_AT_SYNAPSES UP"
## [17] "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION UP"
## [18] "REACTOME_OPIOID_SIGNALLING UP"
## [19] "REACTOME_G_PROTEIN_MEDIATED_EVENTS UP"
## [20] "REACTOME_MUSCLE_CONTRACTION UP"
## [21] "REACTOME_COLLAGEN_FORMATION UP"
## [22] "REACTOME_ASSEMBLY_OF_COLLAGEN_FIBRILS_AND_OTHER_MULTIMERIC_STRUCTURES UP"
## [23] "REACTOME_RAC2_GTPASE_CYCLE UP"
## [24] "REACTOME_STIMULI_SENSING_CHANNELS UP"
## [25] "REACTOME_CELL_CELL_COMMUNICATION UP"
## [26] "REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS UP"
## [27] "REACTOME_INTEGRIN_CELL_SURFACE_INTERACTIONS UP"
## [28] "REACTOME_HEPARAN_SULFATE_HEPARIN_HS_GAG_METABOLISM UP"
## [29] "REACTOME_CELL_CELL_JUNCTION_ORGANIZATION UP"
## [30] "REACTOME_PLATELET_HOMEOSTASIS UP"
## [31] "REACTOME_REGULATION_OF_INSULIN_SECRETION UP"
## [32] "REACTOME_TRAFFICKING_OF_AMPA_RECEPTORS UP"
## [33] "REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS UP"
## [34] "REACTOME_THE_ROLE_OF_NEF_IN_HIV_1_REPLICATION_AND_DISEASE_PATHOGENESIS UP"
## [35] "REACTOME_G_ALPHA_12_13_SIGNALLING_EVENTS UP"
## [36] "REACTOME_NEUREXINS_AND_NEUROLIGINS UP"
## [37] "REACTOME_LAMININ_INTERACTIONS UP"
## [38] "REACTOME_RHOQ_GTPASE_CYCLE UP"
## [39] "REACTOME_CARDIAC_CONDUCTION UP"
## [40] "REACTOME_TRANSPORT_OF_INORGANIC_CATIONS_ANIONS_AND_AMINO_ACIDS_OLIGOPEPTIDES UP"
## [41] "REACTOME_GPCR_LIGAND_BINDING UP"
## [42] "REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK UP"
## [43] "REACTOME_FGFR1_MUTANT_RECEPTOR_ACTIVATION UP"
## [44] "REACTOME_ION_CHANNEL_TRANSPORT UP"
## [45] "REACTOME_RET_SIGNALING UP"
## [46] "REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS UP"
## [47] "REACTOME_EFFECTS_OF_PIP2_HYDROLYSIS UP"
## [48] "REACTOME_RAC3_GTPASE_CYCLE UP"
## [49] "REACTOME_NETRIN_1_SIGNALING UP"
## [50] "REACTOME_METABOLISM_OF_LIPIDS DN"
## [51] "REACTOME_TRANSPORT_OF_SMALL_MOLECULES DN"
## [52] "REACTOME_ADAPTIVE_IMMUNE_SYSTEM DN"
## [53] "REACTOME_HEMOSTASIS DN"
## [54] "REACTOME_RHO_GTPASE_CYCLE DN"
## [55] "REACTOME_NEURONAL_SYSTEM DN"
## [56] "REACTOME_PHOSPHOLIPID_METABOLISM DN"
## [57] "REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION DN"
## [58] "REACTOME_FATTY_ACID_METABOLISM DN"
## [59] "REACTOME_ION_CHANNEL_TRANSPORT DN"
## [60] "REACTOME_SLC_MEDIATED_TRANSMEMBRANE_TRANSPORT DN"
## [61] "REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION DN"
## [62] "REACTOME_VESICLE_MEDIATED_TRANSPORT DN"
## [63] "REACTOME_NEUTROPHIL_DEGRANULATION DN"
## [64] "REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION DN"
## [65] "REACTOME_MEMBRANE_TRAFFICKING DN"
## [66] "REACTOME_DISEASES_OF_METABOLISM DN"
## [67] "REACTOME_MITOTIC_METAPHASE_AND_ANAPHASE DN"
## [68] "REACTOME_RAC1_GTPASE_CYCLE DN"
## [69] "REACTOME_ORGANELLE_BIOGENESIS_AND_MAINTENANCE DN"
## [70] "REACTOME_METABOLISM_OF_CARBOHYDRATES DN"
## [71] "REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES DN"
## [72] "REACTOME_GLYCEROPHOSPHOLIPID_BIOSYNTHESIS DN"
## [73] "REACTOME_MITOTIC_PROMETAPHASE DN"
## [74] "REACTOME_CILIUM_ASSEMBLY DN"
## [75] "REACTOME_NEUROTRANSMITTER_RECEPTORS_AND_POSTSYNAPTIC_SIGNAL_TRANSMISSION DN"
## [76] "REACTOME_METABOLISM_OF_STEROIDS DN"
## [77] "REACTOME_INTRACELLULAR_SIGNALING_BY_SECOND_MESSENGERS DN"message("discordant")## discordantintersect( sapply(strsplit(LAMspec," "),"[[",1) , sapply(strsplit(GSAspec," "),"[[",1) )## [1] "REACTOME_MITOTIC_METAPHASE_AND_ANAPHASE"
## [2] "REACTOME_INTRACELLULAR_SIGNALING_BY_SECOND_MESSENGERS"
## [3] "REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION"
## [4] "REACTOME_MITOTIC_PROMETAPHASE"
## [5] "REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION"
## [6] "REACTOME_ORGANELLE_BIOGENESIS_AND_MAINTENANCE"
## [7] "REACTOME_METABOLISM_OF_CARBOHYDRATES"Now look at the size of these genesets. Make sure these are ACTUALLY detected. Make a vector of genes.
detgenes <- unique(unlist(strsplit(dm$UCSC_RefGene_Name,";")))
gsigsets1 <- sapply(strsplit(gsigsets," "),'[[',1)
gsigsets1set <- gs_symbols[names(gs_symbols) %in% gsigsets1]
gsigsets1len <- unlist(lapply(gsigsets1set,function(set) {
length(set[which(set %in% detgenes)])
}))
lamsigsets1 <- sapply(strsplit(lamsigsets2," "),'[[',1)
lamsigsets1set <- gs_symbols[names(gs_symbols) %in% lamsigsets1]
lamsigsets1len <- unlist(lapply(lamsigsets1set,function(set) {
length(set[which(set %in% detgenes)])
}))
summary(gsigsets1len)## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 26.0 66.5 135.0 219.8 283.5 1266.0summary(lamsigsets1len)## Min. 1st Qu. Median Mean 3rd Qu. Max.
## 5.0 28.0 54.5 104.2 98.0 1292.0GSANAME=paste("GSA (",length(gsigsets1len),")",sep="")
LAMNAME=paste("LAM (",length(lamsigsets1len),")",sep="")
mylist <- list(GSANAME=gsigsets1len,LAMNAME=lamsigsets1len)
boxplot(mylist,cex=0, ylab="gene set size",names=c(GSANAME,LAMNAME))
beeswarm(mylist,pch=19,add=TRUE,cex=0.7)
Make Fig3 an euler diagram, boxplot of sizes and barplot of top results.
png(filename="euler.png",height=75,width=105,units="mm",res=200)
plot(euler(v1),quantities = TRUE)
dev.off()## png
## 2pic <- readPNG("euler.png")
png(filename="fig3.png",height=150,width=210,units="mm",res=200)
par(mar = c(4.5, 4.1, 2.1, 0.5))
par(mfrow=c(2,2))
#A overlap of LAM and GSA results
par(mar = c(2,0,2,0))
plot.new()
plot.window(xlim = c(0 , 1), ylim = c( 0, 1))
rasterImage(pic,0,0,1,1)
par(mar = c(4.5, 4.1, 2.1, 0.5))
#B
par(mar = c(4.5, 4.1, 2.1, 0.5))
boxplot(mylist,cex=0, ylab="gene set size",names=c(GSANAME,LAMNAME))
beeswarm(mylist,pch=1,add=TRUE,cex=0.3)
#C
top <- head(lamsig,20)
top <- top[order(top$s.dist),]
barnames <- gsub("_"," ",gsub("REACTOME_","",rownames(top)))
barnames2 <- substring(barnames, 1, 60)
barnames2 <- paste(barnames2,gsub("TRUE","...",gsub("FALSE","",sapply(barnames,nchar)>60)))
cols <- gsub("TRUE","red",gsub("FALSE","blue",as.character(top$s.dist>0)))
par(mar = c(6.1, 20.1, 1.1, 0.5))
barplot(abs(top$s.dist),horiz=TRUE,las=1,names.arg=barnames2, cex.names=0.55,
cex.axis=0.7,col=cols)
title(main="LAM",cex = 0.8)
title(xlab="S dist",cex=0.6)
grid()
#D
barnames <- gsub("_"," ",gsub("REACTOME_","",rownames(gsiges)))
cols <- gsub("FALSE","blue",gsub("TRUE","red",grepl(" UP",barnames)))
barnames <- gsub("DN","",gsub(" UP","",barnames))
barnames2 <- substring(barnames, 1, 60)
barnames2 <- paste(barnames2,gsub("TRUE","...",gsub("FALSE","",sapply(barnames,nchar)>60)))
par(mar = c(6.1, 20.1, 1.1, 0.5))
barplot(abs(gsiges$ES),horiz=TRUE,las=1,names.arg=barnames2, cex.names=0.55,
cex.axis=0.7, col=cols, xlab="Enrichment score",main="GSA")
grid()
dev.off()## png
## 2Interesting result that shows that LAM detected gene sets are smaller (59.5) than GSA sets (205).
This could be due to one of the quirks in some ORA analyses were genes without an annotation are excluded.
Session information
save.image("GSE158422_sensitivity.Rdata")
sessionInfo()## R version 4.3.2 (2023-10-31)
## Platform: x86_64-pc-linux-gnu (64-bit)
## Running under: Ubuntu 22.04.3 LTS
##
## Matrix products: default
## BLAS: /usr/lib/x86_64-linux-gnu/openblas-pthread/libblas.so.3
## LAPACK: /usr/lib/x86_64-linux-gnu/openblas-pthread/libopenblasp-r0.3.20.so; LAPACK version 3.10.0
##
## locale:
## [1] LC_CTYPE=en_US.UTF-8 LC_NUMERIC=C
## [3] LC_TIME=en_US.UTF-8 LC_COLLATE=en_US.UTF-8
## [5] LC_MONETARY=en_US.UTF-8 LC_MESSAGES=en_US.UTF-8
## [7] LC_PAPER=en_US.UTF-8 LC_NAME=C
## [9] LC_ADDRESS=C LC_TELEPHONE=C
## [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C
##
## time zone: Etc/UTC
## tzcode source: system (glibc)
##
## attached base packages:
## [1] parallel stats4 stats graphics grDevices utils datasets
## [8] methods base
##
## other attached packages:
## [1] png_0.1-8
## [2] gridExtra_2.3
## [3] missMethyl_1.36.0
## [4] IlluminaHumanMethylation450kanno.ilmn12.hg19_0.6.1
## [5] beeswarm_0.4.0
## [6] kableExtra_1.3.4
## [7] mitch_1.15.0
## [8] tictoc_1.2
## [9] HGNChelper_0.8.1
## [10] IlluminaHumanMethylationEPICanno.ilm10b4.hg19_0.6.0
## [11] IlluminaHumanMethylation450kmanifest_0.4.0
## [12] minfi_1.48.0
## [13] bumphunter_1.44.0
## [14] locfit_1.5-9.8
## [15] iterators_1.0.14
## [16] foreach_1.5.2
## [17] Biostrings_2.70.1
## [18] XVector_0.42.0
## [19] SummarizedExperiment_1.32.0
## [20] Biobase_2.62.0
## [21] MatrixGenerics_1.14.0
## [22] matrixStats_1.2.0
## [23] GenomicRanges_1.54.1
## [24] GenomeInfoDb_1.38.2
## [25] IRanges_2.36.0
## [26] S4Vectors_0.40.2
## [27] BiocGenerics_0.48.1
## [28] eulerr_7.0.0
## [29] limma_3.58.1
##
## loaded via a namespace (and not attached):
## [1] splines_4.3.2 later_1.3.2
## [3] BiocIO_1.12.0 bitops_1.0-7
## [5] filelock_1.0.3 BiasedUrn_2.0.11
## [7] tibble_3.2.1 polyclip_1.10-6
## [9] preprocessCore_1.64.0 XML_3.99-0.16
## [11] lifecycle_1.0.4 lattice_0.22-5
## [13] MASS_7.3-60 base64_2.0.1
## [15] scrime_1.3.5 magrittr_2.0.3
## [17] sass_0.4.8 rmarkdown_2.25
## [19] jquerylib_0.1.4 yaml_2.3.8
## [21] httpuv_1.6.13 doRNG_1.8.6
## [23] askpass_1.2.0 DBI_1.1.3
## [25] RColorBrewer_1.1-3 abind_1.4-5
## [27] zlibbioc_1.48.0 rvest_1.0.3
## [29] quadprog_1.5-8 purrr_1.0.2
## [31] RCurl_1.98-1.13 rappdirs_0.3.3
## [33] GenomeInfoDbData_1.2.11 genefilter_1.84.0
## [35] annotate_1.80.0 svglite_2.1.3
## [37] DelayedMatrixStats_1.24.0 codetools_0.2-19
## [39] DelayedArray_0.28.0 xml2_1.3.6
## [41] tidyselect_1.2.0 beanplot_1.3.1
## [43] BiocFileCache_2.10.1 webshot_0.5.5
## [45] illuminaio_0.44.0 GenomicAlignments_1.38.0
## [47] jsonlite_1.8.8 multtest_2.58.0
## [49] ellipsis_0.3.2 survival_3.5-7
## [51] systemfonts_1.0.5 polylabelr_0.2.0
## [53] tools_4.3.2 progress_1.2.3
## [55] Rcpp_1.0.11 glue_1.6.2
## [57] SparseArray_1.2.2 xfun_0.41
## [59] dplyr_1.1.4 HDF5Array_1.30.0
## [61] fastmap_1.1.1 GGally_2.2.0
## [63] rhdf5filters_1.14.1 fansi_1.0.6
## [65] openssl_2.1.1 caTools_1.18.2
## [67] digest_0.6.33 R6_2.5.1
## [69] mime_0.12 colorspace_2.1-0
## [71] gtools_3.9.5 biomaRt_2.58.0
## [73] RSQLite_2.3.4 utf8_1.2.4
## [75] tidyr_1.3.0 generics_0.1.3
## [77] data.table_1.14.10 rtracklayer_1.62.0
## [79] prettyunits_1.2.0 httr_1.4.7
## [81] htmlwidgets_1.6.4 S4Arrays_1.2.0
## [83] ggstats_0.5.1 pkgconfig_2.0.3
## [85] gtable_0.3.4 blob_1.2.4
## [87] siggenes_1.76.0 htmltools_0.5.7
## [89] echarts4r_0.4.5 scales_1.3.0
## [91] rstudioapi_0.15.0 knitr_1.45
## [93] reshape2_1.4.4 tzdb_0.4.0
## [95] rjson_0.2.21 nlme_3.1-163
## [97] curl_5.2.0 org.Hs.eg.db_3.18.0
## [99] cachem_1.0.8 rhdf5_2.46.1
## [101] stringr_1.5.1 KernSmooth_2.23-22
## [103] AnnotationDbi_1.64.1 restfulr_0.0.15
## [105] GEOquery_2.70.0 pillar_1.9.0
## [107] grid_4.3.2 reshape_0.8.9
## [109] vctrs_0.6.5 gplots_3.1.3
## [111] promises_1.2.1 dbplyr_2.4.0
## [113] xtable_1.8-4 evaluate_0.23
## [115] readr_2.1.4 GenomicFeatures_1.54.1
## [117] cli_3.6.2 compiler_4.3.2
## [119] Rsamtools_2.18.0 rlang_1.1.2
## [121] crayon_1.5.2 rngtools_1.5.2
## [123] nor1mix_1.3-2 mclust_6.0.1
## [125] plyr_1.8.9 stringi_1.8.3
## [127] viridisLite_0.4.2 BiocParallel_1.36.0
## [129] munsell_0.5.0 Matrix_1.6-1.1
## [131] hms_1.1.3 sparseMatrixStats_1.14.0
## [133] bit64_4.0.5 ggplot2_3.4.4
## [135] Rhdf5lib_1.24.1 KEGGREST_1.42.0
## [137] statmod_1.5.0 shiny_1.8.0
## [139] highr_0.10 memoise_2.0.1
## [141] bslib_0.6.1 bit_4.0.5