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Prim_Lib2
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#####
# libraries for the primate analysis
# Use with AnalyzePrim.R
# From paper -> doi:10.1038/nature10532
load.Hum.exp <- function(){
humExp <- read.table(as.matrix("Documents/primate_mac/Human_Ensembl57_TopHat_UniqueReads.txt"),header=TRUE)
humExp <- humExp[humExp$Chr != "X" & humExp$Chr != "Y",]
## Remove samples with no expression
mTest <- apply(X=humExp[,-c(1:6)],MARGIN=2,FUN=mean)
#sTest <- apply(X=humExp[,-c(1:6)],MARGIN=2,FUN=sd)
rm <- ""
for (i in 1:length(mTest)){
if (mTest[i] == 0){
rm <- c(rm,i)
}
}
rm <- as.numeric(rm[-c(1)]) + 6
if (length(rm) > 0){
humExp <- humExp[,-c(rm)]
}
return(humExp)
}
load.Prim.exp <- function (prim){
if (prim == "RheMac"){
primExp <- read.table(as.matrix("Documents/primate_mac/Macaque_Ensembl57_TopHat_UniqueReads.txt"),header=TRUE)
}else if (prim == "GorGor"){
primExp <- read.table(as.matrix("Documents/primate_mac/Gorilla_Ensembl57_TopHat_UniqueReads.txt"),header=TRUE)
}else if (prim == "Chimp"){
primExp <- read.table(as.matrix("Documents/primate_mac/Chimpanzee_Ensembl57_TopHat_UniqueReads.txt"),header=TRUE)
}else if (prim == "Orangutan"){
primExp <- read.table(as.matrix("Documents/primate_mac/Orangutan_Ensembl57_TopHat_UniqueReads.txt"),header=TRUE)
}else if (prim == "Bonobo"){
primExp <- read.table(as.matrix("Documents/primate_mac/Bonobo_Ensembl57_TopHat_UniqueReads.txt"),header=TRUE)
}
primExp <- primExp[primExp$Chr != "X" & primExp$Chr != "Y",]
mTest <- apply(X=primExp[,-c(1:6)],MARGIN=2,FUN=mean)
#sTest <- apply(X=primExp[,-c(1:6)],MARGIN=2,FUN=sd)
rm <- ""
for (i in 1:length(mTest)){
if (mTest[i] == 0){
rm <- c(rm,i)
}
}
rm <- as.numeric(rm[-c(1)])+ 6
if (length(rm) > 0){
primExp <- primExp[,-c(rm)]
}
return(primExp)
}
load.polymorphisms <- function(polyGenes.frame,test.type){
nomen <- c("chr","start","stop","GeneID","score","stranda","strandb","dis")
if (length(colnames(polyGenes.frame)) == length(nomen)){
colnames(polyGenes.frame) <- c("chr","start","stop","GeneID","score","stranda","strandb","dis")
}else if (regexpr("ExonReg",text=test.type)[1] >=1){
colnames(polyGenes.frame) <- c("chr","start","stop","GeneID","score","stranda","strandb","dis")
}else{
colnames(polyGenes.frame) <- c("chr","start","stop","GeneID","score","strand")
}
return(polyGenes.frame)
}
get.poly.genes <- function (polyGenes.frame,count.test){
#grab genes that contain a polymorphic element
count <- table(polyGenes.frame$GeneID)
polyGenes <- data.frame(names(count),count)
polyGenes <- polyGenes[,-c(1)]
# colnames(polyGenes) <- c("GeneID","count")
if (count.test == FALSE){
polyGenes <- as.data.frame(polyGenes[polyGenes$count ==1,])
colnames(polyGenes) <- c("GeneID","count")
}
else{
polyGenes <- as.data.frame(polyGenes.frame$GeneID)
}
return(polyGenes)
}
hum.orthologs <- function (humExp,orth,prim){
colnames(orth) <- c("GeneID","Chimpanzee","Gorilla","Orangutan","Macaque")
if (prim == "RheMac"){
primGeneID <- join(orth,humExp,by="GeneID")[,c(1,5)]
#primGeneID <- na.exclude(orth[match(orth$Human,humExp$GeneID),][c(1,5)])
colnames(primGeneID) <- c("GeneID","Macaque")
}else if (prim == "GorGor"){
primGeneID <- join(orth,humExp,by="GeneID")[,c(1,3)]
#primGeneID <- na.exclude(orth[match(orth$Human,humExp$GeneID),][c(1,3)])
colnames(primGeneID) <- c("GeneID","Gorilla")
}else if (prim == "Chimp"){
primGeneID <- join(orth,humExp,by="GeneID")[,c(1,2)]
#primGeneID <- na.exclude(orth[match(orth$Human,humExp$GeneID),][c(1,2)])
colnames(primGeneID) <- c("GeneID","Chimpanzee")
}else if (prim == "Orangutan"){
primGeneID <- join(orth,humExp,by="GeneID")[,c(1,4)]
#primGeneID <- na.exclude(orth[match(orth$Human,humExp$GeneID),][c(1,4)])
colnames(primGeneID) <- c("GeneID","Orangutan")
}
humExp2 <- join(primGeneID,humExp,by="GeneID",type="inner",match="all")
return(humExp2)
}
prim.orthologs <- function (primExp,orth,prim){
if (prim == "RheMac"){
#humGeneID <- na.exclude(orth[match(orth$Macaque,primExp$GeneID),][c(1,5)])
colnames(orth) <- c("Human","Chimpanzee","Gorilla","Orangutan","GeneID")
humGeneID <- join(orth,primExp,by="GeneID")[,c(1,5)]
colnames(humGeneID) <- c("Human","GeneID")
}else if (prim == "GorGor"){
#humGeneID <- na.exclude(orth[match(orth$Gorilla,primExp$GeneID),][c(1,3)])
colnames(orth) <- c("Human","Chimpanzee","GeneID","Orangutan","Macaque")
humGeneID <- join(orth,primExp,by="GeneID")[,c(1,3)]
colnames(humGeneID) <- c("Human","GeneID")
}else if (prim == "Chimp"){
#humGeneID <- na.exclude(orth[match(orth$Chimpanzee,primExp$GeneID),][c(1,2)])
colnames(orth) <- c("Human","GeneID","Gorilla","Orangutan","Macaque")
humGeneID <- join(orth,primExp,by="GeneID")[,c(1,2)]
colnames(humGeneID) <- c("Human","GeneID")
}else if (prim == "Orangutan"){
#humGeneID <- na.exclude(orth[match(orth$Orangutan,primExp$GeneID),][c(1,4)])
colnames(orth) <- c("Human","Chimpanzee","Gorilla","GeneID","Macaque")
humGeneID <- join(orth,primExp,by="GeneID")[,c(1,4)]
colnames(humGeneID) <- c("Human","GeneID")
}
primExp <- join(humGeneID,primExp,by="GeneID",type="inner",match="all")
return(primExp)
}
poly.expression <- function (humExp2,primExp2,polyGenes,polyGenes.frame,test.type,type){
#make sure that hum and primate have the same #rows
# once the polyGenes are selected (need to double back to do this)
#1.)match hum to poly genes
if(ncol(polyGenes) == 2){
colnames(polyGenes) <- c("GeneID","count")
}else if (ncol(polyGenes) == 1){
colnames(polyGenes) <- c("GeneID")
}
humPolyExp <- join(humExp2,unique(polyGenes),by="GeneID",type="inner",match="all") #CHANGED HERE
#humPolyExp2 <- merge(x=humPolyExp,y=unique(polyGenes),by="GeneID")
#2.)match prim to those that hum matched
if(ncol(polyGenes) == 2){
colnames(polyGenes) <- c("Human","count")
}else if (ncol(polyGenes) == 1){
colnames(polyGenes) <- c("Human")
}
primPolyExp <- join(x=primExp2,y=unique(polyGenes),by="Human",type="inner",match="all")#CHANGE first -. all here
#primPolyExp <- merge(x=primPolyExp,y=unique(polyGenes),by.y="Human",by.x="Human")
#3.)double back: match hum to those that prim matched
colnames(humPolyExp) <- c("Human",colnames(humPolyExp[,-c(1)]))
humPolyExp2 <- join(humPolyExp,primPolyExp,by="Human",type="inner",match="first")
primPolyExp2 <- join(primPolyExp,humPolyExp,by="Human",type="inner",match="first")
colnames(humPolyExp) <- c("GeneID",colnames(humPolyExp[,-c(1)]))
if (regexpr("ExonReg",text=test.type)[1] >=1 ){
h <- humPolyExp2[,-c(27:44)]
#humPolyExp2 <- merge(h,polyGenes.frame,by="GeneID")
humPolyExp2 <- join(h,polyGenes.frame,by="GeneID",match="all")#changed first to all
}
if (type == "human"){
return(humPolyExp2)
}else{
return(primPolyExp2)
}
}
cons.expression <- function (humExp,humPolyExp,primExp,primPolyExp) {
humPolyGenes <- humExp[match(humExp$GeneID,humPolyExp$GeneID),][2]
compare <- data.frame(humExp$GeneID,humPolyGenes[,1])
#Get genes that are not polymorphic
humConsGenes <- as.data.frame(compare[(is.na(compare[,2] == TRUE)),][,1])
colnames(humConsGenes) <- c("GeneID")
humExp$GeneID <- as.factor(humExp$GeneID)
humConsExp <- join(humExp,humConsGenes,by="GeneID",type="inner",match="all")#CHANGE first to all
#remove instances where primate doesn't have an orth. gene
humConsExp <- na.exclude(humConsExp)
primPolyGenes <- primExp[match(primExp$GeneID,primPolyExp$GeneID),][2]
compare <- data.frame(primExp$GeneID,primPolyGenes[,1])
primConsGenes <- compare[(is.na(compare[,2] == TRUE)),][,1]
primConsExp <- primExp[match(primConsGenes,primExp$GeneID,nomatch=FALSE),]
#remove instances where primate doesn't have an orth. gene
primConsExp <- na.exclude(primConsExp)
colnames(humConsExp) <- c("Human",colnames(humConsExp[,-c(1)]))
primConsExp <- join(primConsExp,humConsExp,by="Human",type="inner",match="all")#CHANGED first -> all here
humConsExp <- join(humConsExp,primConsExp,by="Human",type="inner",match="all")#CHANGED first -> all here
if (type == "human"){
return(humConsExp)
}else{
return(primConsExp)
}
}
tissue.values <- function (tissue,prim,humPolyExp,humConsExp,primPolyExp,primConsExp,type) {
###Average over tissue depending on the species, tissue type, and sex
if (tissue == "brain"){
if (sex.specific == "male"){
hPolymean <- apply(X=humPolyExp[,c(9:13)],MARGIN=1,FUN=mean)
hConsmean <- apply(X=humConsExp[,c(9:13)],MARGIN=1,FUN=mean)
if (prim == "RheMac" | prim == "GorGor" | prim == "Orangutan"){
pPolymean <- primPolyExp[,c(9)]
pConsmean <- primConsExp[,c(9)]
}else if (prim == "Chimp"){
pPolymean <- apply(X=primPolyExp[,c(8:12)],MARGIN=1,FUN=mean)
pConsmean <- apply(X=primConsExp[,c(8:12)],MARGIN=1,FUN=mean)
}else{
pPolymean <- NA
pConsmean <- NA
}
}else if (sex.specific == "female"){
hPolymean <- humPolyExp[,c(8)]
hConsmean <- humConsExp[,c(8)]
if (prim == "RheMac"| prim == "GorGor"| prim == "Orangutan"){
pPolymean <- primPolyExp[,c(8)]
pConsmean <- primConsExp[,c(8)]
}else if (prim == "Chimp"){
pPolymean <- primPolyExp[,c(13)]
pConsmean <- primConsExp[,c(13)]
}else{
pPolymean <- NA
pConsmean <- NA
}
}else{
hPolymean <- apply(X=humPolyExp[,c(8:13)],MARGIN=1,FUN=mean)
hConsmean <- apply(X=humConsExp[,c(8:13)],MARGIN=1,FUN=mean)
if (prim == "RheMac"| prim == "GorGor"){
pPolymean <- apply(X=primPolyExp[,c(8:9)],MARGIN=1,FUN=mean)
pConsmean <- apply(X=primConsExp[,c(8:9)],MARGIN=1,FUN=mean)
}else{
pPolymean <- NA
pConsmean <- NA
}
}
}else if (tissue == "cerebellum"){
if (sex.specific == "male"){
hPolymean <- humPolyExp[,c(15)]
hConsmean <- humConsExp[,c(15)]
if (prim == "RheMac"| prim == "GorGor"| prim == "Orangutan"){
pPolymean <- primPolyExp[,c(11)]
pConsmean <- primConsExp[,c(11)]
}else if (prim == "Chimp"){
pPolymean <- primPolyExp[,c(14)]
pConsmean <- primConsExp[,c(14)]
}else{
pPolymean <- NA
pConsmean <- NA
}
}else if (sex.specific == "female"){
hPolymean <- humPolyExp[,c(14)]
hConsmean <- humConsExp[,c(14)]
if (prim == "RheMac"| prim == "GorGor"| prim == "Orangutan"){
pPolymean <- primPolyExp[,c(10)]
pConsmean <- primConsExp[,c(10)]
}else if (prim == "Chimp"){
pPolymean <- primPolyExp[,c(15)]
pConsmean <- primConsExp[,c(15)]
}else{
pPolymean <- NA
pConsmean <- NA
}
}else{
hPolymean <- apply(X=humPolyExp[,c(14:15)],MARGIN=1,FUN=mean)
hConsmean <- apply(X=humConsExp[,c(14:15)],MARGIN=1,FUN=mean)
if (prim == "RheMac"| prim == "GorGor"){
pPolymean <- apply(X=primPolyExp[,c(10:11)],MARGIN=1,FUN=mean)
pConsmean <- apply(X=primConsExp[,c(10:11)],MARGIN=1,FUN=mean)
}else{
pPolymean <- NA
pConsmean <- NA
}
}
}else if (tissue == "heart"){
if (sex.specific == "male"){
hPolymean <- apply(X=humPolyExp[,c(17:18)],MARGIN=1,FUN=mean)
hConsmean <- apply(X=humConsExp[,c(17:18)],MARGIN=1,FUN=mean)
if (prim == "RheMac"| prim == "GorGor"| prim == "Orangutan"){
pPolymean <- primPolyExp[,c(13)]
pConsmean <- primConsExp[,c(13)]
}else if (prim == "Chimp"){
pPolymean <- primPolyExp[,c(16)]
pConsmean <- primConsExp[,c(16)]
}else{
pPolymean <- NA
pConsmean <- NA
}
}else if (sex.specific == "female"){
hPolymean <- humPolyExp[,c(16)]
hConsmean <- humConsExp[,c(16)]
if (prim == "RheMac"| prim == "GorGor"| prim == "Orangutan"){
pPolymean <- primPolyExp[,c(12)]
pConsmean <- primConsExp[,c(12)]
}else if (prim == "Chimp"){
pPolymean <- primPolyExp[,c(17)]
pConsmean <- primConsExp[,c(17)]
}else{
pPolymean <- NA
pConsmean <- NA
}
}else{
hPolymean <- apply(X=humPolyExp[,c(16:18)],MARGIN=1,FUN=mean)
hConsmean <- apply(X=humConsExp[,c(16:18)],MARGIN=1,FUN=mean)
if (prim == "RheMac"| prim == "GorGor"){
pPolymean <- apply(X=primPolyExp[,c(12:13)],MARGIN=1,FUN=mean)
pConsmean <- apply(X=primConsExp[,c(12:13)],MARGIN=1,FUN=mean)
}else{
pPolymean <- NA
pConsmean <- NA
}
}
}else if (tissue == "kidney"){
if (sex.specific == "male"){
hPolymean <- apply(X=humPolyExp[,c(20:21)],MARGIN=1,FUN=mean)
hConsmean <- apply(X=humConsExp[,c(20:21)],MARGIN=1,FUN=mean)
if (prim == "RheMac"| prim == "GorGor"| prim == "Orangutan"){
pPolymean <- primPolyExp[,c(15)]
pConsmean <- primConsExp[,c(15)]
}else if (prim == "Chimp"){
pPolymean <- primPolyExp[,c(18)]
pConsmean <- primConsExp[,c(18)]
}else{
pPolymean <- NA
pConsmean <- NA
}
}else if (sex.specific == "female"){
hPolymean <- humPolyExp[,c(19)]
hConsmean <- humConsExp[,c(19)]
if (prim == "RheMac"| prim == "GorGor"| prim == "Orangutan"){
pPolymean <- primPolyExp[,c(14)]
pConsmean <- primConsExp[,c(14)]
}else if (prim == "Chimp"){
pPolymean <- primPolyExp[,c(19)]
pConsmean <- primConsExp[,c(19)]
}else{
pPolymean <- NA
pConsmean <- NA
}
}else{
hPolymean <- apply(X=humPolyExp[,c(19:21)],MARGIN=1,FUN=mean)
hConsmean <- apply(X=humConsExp[,c(19:21)],MARGIN=1,FUN=mean)
if (prim == "RheMac"| prim == "GorGor"){
pPolymean <- apply(X=primPolyExp[,c(14:15)],MARGIN=1,FUN=mean)
pConsmean <- apply(X=primConsExp[,c(14:15)],MARGIN=1,FUN=mean)
}else{
pPolymean <- NA
pConsmean <- NA
}
}
}else if (tissue == "liver"){
if (sex.specific == "male"){
hPolymean <- apply(X=humPolyExp[,c(22:23)],MARGIN=1,FUN=mean)
hConsmean <- apply(X=humConsExp[,c(22:23)],MARGIN=1,FUN=mean)
if (prim == "RheMac"| prim == "GorGor"| prim == "Orangutan"){
pPolymean <- primPolyExp[,c(17)]
pConsmean <- primConsExp[,c(17)]
}else if (prim == "Chimp"){
pPolymean <- primPolyExp[,c(20)]
pConsmean <- primConsExp[,c(20)]
}else{
pPolymean <- NA
pConsmean <- NA
}
}else if (sex.specific == "female"){
hPolymean <- NA
hConsmean <- NA
if (prim == "RheMac"| prim == "GorGor"| prim == "Orangutan"){
pPolymean <- primPolyExp[,c(16)]
pConsmean <- primConsExp[,c(16)]
}else if (prim == "Chimp"){
pPolymean <- primPolyExp[,c(21)]
pConsmean <- primConsExp[,c(21)]
}else{
pPolymean <- NA
pConsmean <- NA
}
}else{
hPolymean <- apply(X=humPolyExp[,c(22:23)],MARGIN=1,FUN=mean)
hConsmean <- apply(X=humConsExp[,c(22:23)],MARGIN=1,FUN=mean)
if (prim == "RheMac"| prim == "GorGor"){
pPolymean <- apply(X=primPolyExp[,c(16:17)],MARGIN=1,FUN=mean)
pConsmean <- apply(X=primConsExp[,c(16:17)],MARGIN=1,FUN=mean)
}else{
pPolymean <- NA
pConsmean <- NA
}
}
}else if (tissue == "testis"){
if (sex.specific == "male"){
hPolymean <- apply(X=humPolyExp[,c(24:25)],MARGIN=1,FUN=mean)
hConsmean <- apply(X=humConsExp[,c(24:25)],MARGIN=1,FUN=mean)
if (prim == "RheMac"| prim == "GorGor"| prim == "Orangutan"){
pPolymean <- primPolyExp[,c(18)]
pConsmean <- primConsExp[,c(18)]
}else if (prim == "Chimp"){
pPolymean <- primPolyExp[,c(22)]
pConsmean <- primConsExp[,c(22)]
}else{
pPolymean <- NA
pConsmean <- NA
}
}else if (sex.specific == "female"){
hPolymean <- NA
hConsmean <- NA
pPolymean <- NA
pConsmean <- NA
}else{
hPolymean <- apply(X=humPolyExp[,c(24:25)],MARGIN=1,FUN=mean)
hConsmean <- apply(X=humConsExp[,c(24:25)],MARGIN=1,FUN=mean)
if (prim == "RheMac"| prim == "GorGor"| prim == "Orangutan"){
pPolymean <- primPolyExp[,c(18)]
pConsmean <- primConsExp[,c(18)]
}else{
pPolymean <- NA
pConsmean <- NA
}
}
}
if (type =="poly"){
df <- data.frame(hPolymean,pPolymean)
}else{
df <- data.frame(hConsmean,pConsmean)
}
return(df)
}
fisher <- function(minFC,poly.frame,cons.frame){
hPolymean <- poly.frame$hPolymean
pPolymean <- poly.frame$pPolymean
hConsmean <- cons.frame$hConsmean
pConsmean <- cons.frame$pConsmean
CalcPoly.df2 <- data.frame(hPolymean,pPolymean)
CalcCons.df2 <- data.frame(hConsmean,pConsmean)
# Determine which of the polymorphic genes are higher in hum or primate
if (length(minFC) == 1){#if using a minimum fold change
DirPoly2 <- CalcPoly.df2$hPolymean-CalcPoly.df2$pPolymean > minFC
DirCons2 <- ( CalcCons.df2$hConsmean- CalcCons.df2$pConsmean) > minFC
DirPoly1 <- CalcPoly.df2$hPolymean-CalcPoly.df2$pPolymean < -1 * minFC
DirCons1 <- ( CalcCons.df2$hConsmean- CalcCons.df2$pConsmean) < -1 * minFC
}else{
DirPoly1 <- CalcPoly.df2$hPolymean < CalcPoly.df2$pPolymean #hless than
DirCons1 <- CalcCons.df2$hConsmean < CalcCons.df2$pConsmean
DirPoly2 <- CalcPoly.df2$hPolymean > CalcPoly.df2$pPolymean
DirCons2 <- CalcCons.df2$hConsmean > CalcCons.df2$pConsmean
}
#FISCHER TEST
cons <- c(length(DirCons2[DirCons2 == "TRUE"]),length(DirCons1[DirCons1 == "TRUE"]))
poly <- c(length(DirPoly2[DirPoly2 == "TRUE"]),length(DirPoly1[DirPoly1 == "TRUE"]))
df <- data.frame(poly,cons)
rownames(df) <- c("human.greater","human.less")
return(df)
# f <- (fisher.test(x=df))
# f$cons <- cons
# f$poly <- poly
# return(f)
}
regression.frame <- function (poly.frame,cons.frame,humPolyExp,primPolyExp,minFC){
hPolymean <- poly.frame$hPolymean
pPolymean <- poly.frame$pPolymean
hConsmean <- cons.frame$hConsmean
pConsmean <- cons.frame$pConsmean
model.expUP <- ((hPolymean - pPolymean) > minFC) * 2
model.expDOWN <- ((hPolymean - pPolymean) < (-1 * minFC))*1
model.exp <- model.expUP + model.expDOWN
model.bin <- c(humPolyExp[,33] )
model.sub <- c(humPolyExp$score)
model.dis <- c(humPolyExp$ExonicLength)
model.length <- c(humPolyExp$End - humPolyExp$Begin)
model.poly <- c(rep(1,times=nrow(humPolyExp)))
model.orient <- c(as.character(humPolyExp$stranda) == as.character(humPolyExp$strandb))
dftest <- na.exclude(data.frame(model.exp,model.bin,model.dis,model.poly,model.sub,model.orient,model.length))
colnames(dftest) <- c("exp","bin","dis","poly","sub","orient","length")
dftest <- dftest[dftest[,1] != Inf & dftest[,1] != -Inf ,]
dftest <- dftest[dftest$exp !=0,]
return(dftest)
}