diff --git a/README.md b/README.md
index d44d563b63ce8f6d904c85e4734207537005ed4e..e09eba1b33cc2f0f658d1015875840947a9319a3 100755
--- a/README.md
+++ b/README.md
@@ -2,36 +2,36 @@ Author: Min Kim <MinS.Kim@UTSouthwestern.edu> and Spencer Barnes <Spencer.Barnes
Date: April 20, 2017
Description: Shiny app for analyzing TCGA data for frequently asked requests through the Help-Desk.
-Project name Cancer type
-ACC Adrenocortical Carcinoma
-BLCA Bladder Urothelial Carcinoma
-BRCA Breast Invasive Carcinoma
-CESC Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma
-CHOL Cholangiocarcinoma
-COAD Colon Adenocarcinoma
-DLBC Lymphoid Neoplasm Diffuse Large B-cell Lymphoma
-GBM Glioblastoma Multiforme
-HNSC Head and Neck Squamous Cell Carcinoma
-KICH Kidney Chromophobe
-KIRC Kidney Renal Clear Cell Carcinoma
-KIRP Kidney Renal Papillary Cell Carcinoma
-LAML Acute Myeloid Leukemia
-LGG Brain Lower Grade Glioma
-LIHC Liver Hepatocellular Carcinoma
-LUAD Lung Adenocarcinoma
-LUSC Lung Squamous Cell Carcinoma
-MESO Mesothelioma
-OV Ovarian Serous Cystadenocarcinoma
-PAAD Pancreatic Adenocarcinoma
-PCPG Pheochromocytoma and Paraganglioma
-PRAD Prostate Adenocarcinoma
-READ Rectum Adenocarcinoma
-SARC Sarcoma
-SKCM Skin Cutaneous Melanoma
-TGCT Testicular Germ Cell Tumors
-THCA Thyroid Carcinoma
-THYM Thymoma
-UCEC Uterine Corpus Endometrial Carcinoma
-UCS Uterine Carcinosarcoma
-UVM Uveal Melanoma
+Project name Cancer type
+ACC Adrenocortical Carcinoma
+BLCA Bladder Urothelial Carcinoma
+BRCA Breast Invasive Carcinoma
+CESC Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma
+CHOL Cholangiocarcinoma
+COAD Colon Adenocarcinoma
+DLBC Lymphoid Neoplasm Diffuse Large B-cell Lymphoma
+GBM Glioblastoma Multiforme
+HNSC Head and Neck Squamous Cell Carcinoma
+KICH Kidney Chromophobe
+KIRC Kidney Renal Clear Cell Carcinoma
+KIRP Kidney Renal Papillary Cell Carcinoma
+LAML Acute Myeloid Leukemia
+LGG Brain Lower Grade Glioma
+LIHC Liver Hepatocellular Carcinoma
+LUAD Lung Adenocarcinoma
+LUSC Lung Squamous Cell Carcinoma
+MESO Mesothelioma
+OV Ovarian Serous Cystadenocarcinoma
+PAAD Pancreatic Adenocarcinoma
+PCPG Pheochromocytoma and Paraganglioma
+PRAD Prostate Adenocarcinoma
+READ Rectum Adenocarcinoma
+SARC Sarcoma
+SKCM Skin Cutaneous Melanoma
+TGCT Testicular Germ Cell Tumors
+THCA Thyroid Carcinoma
+THYM Thymoma
+UCEC Uterine Corpus Endometrial Carcinoma
+UCS Uterine Carcinosarcoma
+UVM Uveal Melanoma
diff --git a/scripts/server.R b/scripts/server.R
old mode 100755
new mode 100644
index cd4b61d53a94ff20cfe6c734d1fe7fa70b4f8dee..c62a923625f164f937501f09705059eff23239a0
--- a/scripts/server.R
+++ b/scripts/server.R
@@ -4,8 +4,12 @@ library(shinyjs)
library("survival")
library("survminer")
+cat("reading in gene list...")
+all.genes<-read.table("tcga_genes.txt",sep = "\t",header = FALSE)
+all.genes<-as.character(all.genes[,1])
+cat("done\n")
get.filt<-function(var){
- if(var$operation=="Pancan"){
+ if(var$operation=="Boxplot"){
return(
list(
operation=var$operation,
@@ -14,14 +18,26 @@ get.filt<-function(var){
)
)
}else{
- return(
- list(
- operation=var$operation,
- gene=var$gene2,
- cancer=var$cancerType2,
- cutoff=var$cut.off
+ if(var$operation2 == "Manual"){
+ return(
+ list(
+ operation=var$operation,
+ operation2=var$operation2,
+ gene=var$gene2,
+ cancer=var$cancerType2,
+ cutoff=var$cut.off
+ )
)
- )
+ }else if(var$operation2 == "Automatic"){
+ return(
+ list(
+ operation=var$operation,
+ operation2=var$operation2,
+ gene=var$gene2,
+ cancer=var$cancerType2
+ )
+ )
+ }
}
}
@@ -33,143 +49,468 @@ shinyServer(
})
output$myPlot <- renderPlot({
- if(vars()$operation=="Pancan"){
-
- gene<-as.character(vars()$gene)
- cancer.list<-as.character(vars()$cancer.list)
-
- data <- data.frame(value=as.numeric(),type=as.character(),cancer=as.character(),pval=as.numeric())
- pval <- NULL
- for(i in cancer.list){
- if(!file.exists(paste0("../Expression/out_genes/",gene,"/",i,".txt"))){
- cat("File not present\n")
- system(paste0("mkdir ../Expression/out_genes/",gene))
- cat("Made directory/n")
- system(paste("ls ../Expression/*txt | while read line ; do fname=$(basename $line); head -1 $line > ../Expression/out_genes/",
- gene,"/","$fname; grep -wi ",gene," $line >> ../Expression/out_genes/",gene,"/","$fname;done",sep=""))
- cat("creating data\n")
+ #PANCAN BOX PLOT
+ withProgress(message = 'Making plot', value = 0,{
+ if(vars()$operation=="Boxplot"){
+
+ gene<-toupper(gsub("\\s", "", as.character(vars()$gene)))
+ cancer.list<-as.character(vars()$cancer.list)
+ if(!(gene %in% all.genes)){
+ showNotification(paste0("SORRY! ", gene, " is not a valid gene!"), duration = 8, type = "error")
+ }else{
+ data <- data.frame(value=as.numeric(),type=as.character(),cancer=as.character(),pval=as.numeric())
+ pval <- NULL
+ count <- 1
+ n = length(cancer.list) + 1
+ for(i in cancer.list){
+ incProgress(1/n, detail = paste0("collating data ", count, " of ", length(cancer.list)))
+ if(!file.exists(paste0("../Expression/out_genes/",gene,"/",i,".txt"))){
+ cat("File not present\n")
+ if(!dir.exists(paste0("../Expression/out_genes/",gene))){
+ system(paste0("mkdir ../Expression/out_genes/",gene))
+ cat("Made directory\n")
+ }
+ system(paste0("ls ../Expression/*",i,"*txt | while read line ; do fname=$(basename $line); head -1 $line > ../Expression/out_genes/",
+ gene,"/","$fname; grep -wi ",gene," $line >> ../Expression/out_genes/",gene,"/","$fname;done"))
+ cat("creating data\n")
+
+ }
+ temp <- as.data.frame(t(read.table(paste("../Expression/out_genes/",gene,"/",i,".txt",sep=""),header=T,sep="\t",row.names=1)))
+ temp$type <- as.factor(ifelse(grepl("11",row.names(temp)),"Normal","Tumor"))
+ temp$cancer <- rep(i,nrow(temp))
+ if(ncol(temp)<3 | length(unique(temp$type))<2){
+ if(length(cancer.list) > 1){
+ showNotification(paste0("WARNING! Project ", i, " does not have normal tissue data! Skipping..."), duration = 8, type = "warning")
+ next
+ }else{
+ showNotification(paste0("SORRY! Project ", i, " does not have normal tissue data! Choose another project."), duration = 8, type = "error")
+ break
+ }
+
+ }else{
+ colnames(temp) <- c("value","type","cancer")
+ print(i)
+ pval <- c(pval,signif(kruskal.test(value~type,temp)$p.value,2))
+ data <- rbind(data,temp)
+ }
+ count <- count + 1
+ }
+ if(nrow(data)==0){
+ return()
+ }else{
+ data$value <- 2^data$value
+ p <- ggplot(data = data, aes(x=type, y=value)) + geom_boxplot(aes(fill=type),outlier.size = 0.2,outlier.alpha=0.8) + scale_y_continuous(limits = c(0, 2000)) +
+ geom_text(data=data.frame(x=1.5,y=1800,labels=pval,cancer=unique(data$cancer)),aes(x,y,label=labels),size=3 , inherit.aes=FALSE) +
+ theme(panel.grid.major = element_blank(), panel.grid.minor = element_blank(),
+ panel.background = element_blank(), axis.line = element_line(colour = "black"))
+ #cat("printing",gene,"\n")
+ print(p + facet_wrap( ~ cancer, scales="free") + ggtitle(gene) + theme(plot.title = element_text(hjust = 0.5)))
+ incProgress(1/n, detail = paste0("printing plot!"))
+ }
}
- temp <- as.data.frame(t(read.table(paste("../Expression/out_genes/",gene,"/",i,".txt",sep=""),header=T,sep="\t",row.names=1)))
- temp$type <- as.factor(ifelse(grepl("11",row.names(temp)),"Normal","Tumor"))
- temp$cancer <- rep(i,nrow(temp))
- if(ncol(temp)<3 | length(unique(temp$type))<2){
- next
+ #SURVIVAL PLOTS
+ }else if(vars()$operation=="Survival"){
+ #Define Cancer & Gene
+ oldw <- getOption("warn")
+ options(warn = -1)
+ cat("Survival plot\n")
+ cancer <- vars()$cancer
+ gene<-toupper(gsub("\\s", "", as.character(vars()$gene)))
+ cat(paste0(cancer," ",gene,"\n"))
+ if(!(gene %in% all.genes)){
+ showNotification(paste0("SORRY! ", gene, " is not a valid gene!"), duration = 8, type = "error")
}else{
- colnames(temp) <- c("value","type","cancer")
- print(i)
- pval <- c(pval,signif(kruskal.test(value~type,temp)$p.value,2))
- data <- rbind(data,temp)
+ n <- 4
+ incProgress(1/n, detail = "Getting expression data")
+ #Import Expression and Clinical Data
+ cat(paste0("going to read expression ",cancer,"\n"))
+ if(!file.exists(paste0("../Expression/out_genes/",gene,"/",cancer,".txt"))){
+ cat("File not present\n")
+ if(!dir.exists(paste0("../Expression/out_genes/",gene))){
+ system(paste0("mkdir ../Expression/out_genes/",gene))
+ cat("Made directory\n")
+ }
+ system(paste0("ls ../Expression/*",cancer,"*txt | while read line ; do fname=$(basename $line); head -1 $line > ../Expression/out_genes/",
+ gene,"/","$fname; grep -wi ",gene," $line >> ../Expression/out_genes/",gene,"/","$fname;done"))
+ cat("creating data\n")
+
+ }
+ exp <- read.table(paste0("../Expression/out_genes/",gene,"/",cancer,".txt"),header=T,row.names=1,check.names=F)
+ #exp <- read.table(paste0("../Expression/",cancer,".txt"),header=T,row.names=1,check.names=F) #Instead of importing entire expression matrix should import single gene.
+ cat("going to read clinical data\n")
+ incProgress(1/n, detail = "Getting clinical data")
+ clinical <- read.table(paste("../Clinical/",cancer,".txt",sep=""),header=T,row.names=1,sep="\t")
+
+
+ #Process Clinical
+ # get the columns that contain data we can use: days to death, new tumor event, last day contact to....
+ ind_keep <- grep("days_to_new_tumor_event_after_initial_treatment",colnames(clinical))
+
+ # this is a bit tedious, since there are numerous follow ups, let's collapse them together and keep the first value (the higher one) if more than one is available
+ new_tum <- as.matrix(clinical[,ind_keep])
+ new_tum_collapsed <- c()
+ for (i in 1:dim(new_tum)[1]){
+ if(sum(is.na(new_tum[i,])) < dim(new_tum)[2]){
+ m <- min(new_tum[i,],na.rm=T)
+ new_tum_collapsed <- c(new_tum_collapsed,m)
+ } else {
+ new_tum_collapsed <- c(new_tum_collapsed,"NA")
+ }
+ }
+
+ # do the same to death
+ ind_keep <- grep("days_to_death",colnames(clinical))
+ death <- as.matrix(clinical[,ind_keep])
+ death_collapsed <- c()
+ for (i in 1:dim(death)[1]){
+ if(sum(is.na(death[i,])) < dim(death)[2]){
+ m <- max(death[i,],na.rm=T)
+ death_collapsed <- c(death_collapsed,m)
+ } else {
+ death_collapsed <- c(death_collapsed,"NA")
+ }
+ }
+
+ # and days last follow up here we take the most recent which is the max number
+ ind_keep <- grep("days_to_last_followup",colnames(clinical))
+ fl <- as.matrix(clinical[,ind_keep])
+ fl_collapsed <- c()
+ for (i in 1:dim(fl)[1]){
+ if(sum(is.na(fl[i,])) < dim(fl)[2]){
+ m <- max(fl[i,],na.rm=T)
+ fl_collapsed <- c(fl_collapsed,m)
+ } else {
+ fl_collapsed <- c(fl_collapsed,"NA")
+ }
+ }
+
+ # and put everything together
+ all_clin <- data.frame(new_tum_collapsed,death_collapsed,fl_collapsed)
+ colnames(all_clin) <- c("new_tumor_days", "death_days", "followUp_days")
+
+ # create vector with time to new tumor containing data to censor for new_tumor
+ all_clin$new_time <- c()
+ for (i in 1:length(as.numeric(as.character(all_clin$new_tumor_days)))){
+ all_clin$new_time[i] <- ifelse(is.na(as.numeric(as.character(all_clin$new_tumor_days))[i]),
+ as.numeric(as.character(all_clin$followUp_days))[i],as.numeric(as.character(all_clin$new_tumor_days))[i])
+ }
+
+ # create vector time to death containing values to censor for death
+ all_clin$new_death <- c()
+ for (i in 1:length(as.numeric(as.character(all_clin$death_days)))){
+ all_clin$new_death[i] <- ifelse(is.na(as.numeric(as.character(all_clin$death_days))[i]),
+ as.numeric(as.character(all_clin$followUp_days))[i],as.numeric(as.character(all_clin$death_days))[i])
+ }
+
+ all_clin$death_event <- ifelse(clinical$vital_status == "LIVING", 0,1)
+ row.names(all_clin) <- row.names(clinical)
+ colnames(exp) <- gsub("01A","01",colnames(exp))
+ gene.exp <- t(exp[gene,])
+ colnames(gene.exp) <- "gene"
+
+ #Fork for Manual vs Automatic selection
+ if(vars()$operation2 == "Manual"){
+ cutoff <- as.numeric(vars()$cutoff)
+ #Setup Data
+
+ colnames(exp) <- gsub("01A","01",colnames(exp))
+ gene.exp <- t(exp[gene,])
+ colnames(gene.exp) <- "gene"
+ data <- merge(all_clin,gene.exp,by="row.names")
+ data$event_rna <- ifelse(data$gene > quantile(as.numeric(data$gene),1-cutoff),1,0)
+ data <- data[which(data$gene > quantile(as.numeric(data$gene),1-cutoff) | data$gene < quantile(as.numeric(data$gene),cutoff)),]
+ # run survival analysis
+ s <- surv_fit(Surv(as.numeric(as.character(data$new_death)),data$death_event)~event_rna,data)
+ incProgress(1/n, detail = "Printing plot")
+ p<-ggsurvplot(s,conf.int=F,xlab="Time(days)",pval=T,pval.coord=c(1000,0.3),risk.table=TRUE,legend.title="",legend=c(0.8,0.8),legend.labs = c( paste(gene,"LOW",sep=" "), paste(gene,"HIGH",sep=" ")))
+ print(p+ggtitle(paste(cancer, gene,"cutoff: ", cutoff)))
+ options(warn = oldw)
+ }else{
+ cutoff.vals=c(.10, .15, .20, .25, .30, .35, .40, .45, .50)
+ incProgress(1/n, detail = "Checking Cutoffs")
+ for(cutoff in cutoff.vals){
+ cat("\tchecking cutoff value:",cutoff,"\n") ###add status update here
+ data <- merge(all_clin,gene.exp,by="row.names")
+ if(is.na(data$gene)[1]){
+ showNotification(paste0("SORRY! No data for gene ", gene,"!"), duration = 8, type = "error")
+ break
+ }
+ data$event_rna <- ifelse(data$gene > quantile(as.numeric(data$gene),1-cutoff),1,0)
+ data <- data[which(data$gene > quantile(as.numeric(data$gene),1-cutoff) | data$gene < quantile(as.numeric(data$gene),cutoff)),]
+ # run survival analysis
+ if(length(unique(data$event_rna)) < 2){
+ next
+ }
+
+ cat("done!\n")
+ if(cutoff == 0.10){
+ cat("first run\n")
+ best.data <- data
+ best.res <- surv_fit(Surv(as.numeric(as.character(best.data$new_death)),best.data$death_event)~event_rna,best.data)
+ p<-ggsurvplot(best.res,conf.int=F,xlab="Time(days)",pval=TRUE,pval.coord=c(1000,0.3),risk.table=TRUE,legend.title="",legend=c(0.8,0.8),
+ legend.labs = c( paste(gene,"LOW",sep=" "), paste(gene,"HIGH",sep=" ")))
+ best.cutoff <- cutoff
+ }else{
+ s <- surv_fit(Surv(as.numeric(as.character(data$new_death)),data$death_event)~event_rna,data)
+ p<-ggsurvplot(s,conf.int=F,xlab="Time(days)",pval=TRUE,pval.coord=c(1000,0.3),risk.table=TRUE,legend.title="",legend=c(0.8,0.8),
+ legend.labs = c( paste(gene,"LOW",sep=" "), paste(gene,"HIGH",sep=" ")))
+ if((as.numeric(surv_pvalue(s)[2]) < as.numeric(surv_pvalue(best.res)[2])) & (p$table$data$n.risk[1] > 10) & (p$table$data$n.risk[6] > 10)){
+ best.data <- data
+ best.res <- surv_fit(Surv(as.numeric(as.character(best.data$new_death)),best.data$death_event)~event_rna,best.data)
+ p<-ggsurvplot(best.res,conf.int=F,xlab="Time(days)",pval=TRUE,pval.coord=c(1000,0.3),risk.table=TRUE,legend.title="",legend=c(0.8,0.8),
+ legend.labs = c( paste(gene,"LOW",sep=" "), paste(gene,"HIGH",sep=" ")))
+ best.cutoff <- cutoff
+ }
+ }
+
+ }
+ incProgress(1/n, detail = "Printing plot")
+ p <- ggsurvplot(best.res,conf.int=F,xlab="Time(days)",pval=TRUE,pval.coord=c(1000,0.3),risk.table=TRUE,legend.title="",legend=c(0.8,0.8),
+ legend.labs = c( paste(gene,"LOW",sep=" "), paste(gene,"HIGH",sep=" ")))
+ print(p+ggtitle(paste(cancer, "cutoff: ", best.cutoff)))
+
+ }
}
}
+ })
+
+ })
+
+ plotInput = function(){
+ if(vars()$operation=="Boxplot"){
- if(nrow(data)==0){
- cat("Not enough data for this cancer type\n")
+ gene<-toupper(gsub("\\s", "", as.character(vars()$gene)))
+ cancer.list<-as.character(vars()$cancer.list)
+ if(!(gene %in% all.genes)){
+ #showNotification(paste0("SORRY! ", gene, " is not a valid gene!"), duration = 8, type = "error")
}else{
- data$value <- 2^data$value
- p <- ggplot(data = data, aes(x=type, y=value)) + geom_boxplot(aes(fill=type),outlier.size = 0.2,outlier.alpha=0.8) + scale_y_continuous(limits = c(0, 2000)) + geom_text(data=data.frame(x=1.5,y=1800,labels=pval,cancer=cancer.list),aes(x,y,label=labels),size=3 , inherit.aes=FALSE)
- #cat("printing",gene,"\n")
- print(p + facet_wrap( ~ cancer, scales="free") + ggtitle(gene) + theme(plot.title = element_text(hjust = 0.5)))
-
+ data <- data.frame(value=as.numeric(),type=as.character(),cancer=as.character(),pval=as.numeric())
+ pval <- NULL
+ count <- 1
+ n = length(cancer.list) + 1
+ for(i in cancer.list){
+ #incProgress(1/n, detail = paste0("collating data ", count, " of ", length(cancer.list)))
+ if(!file.exists(paste0("../Expression/out_genes/",gene,"/",i,".txt"))){
+ cat("File not present\n")
+ if(!dir.exists(paste0("../Expression/out_genes/",gene))){
+ system(paste0("mkdir ../Expression/out_genes/",gene))
+ cat("Made directory\n")
+ }
+ system(paste0("ls ../Expression/*",i,"*txt | while read line ; do fname=$(basename $line); head -1 $line > ../Expression/out_genes/",
+ gene,"/","$fname; grep -wi ",gene," $line >> ../Expression/out_genes/",gene,"/","$fname;done"))
+ cat("creating data\n")
+
+ }
+ temp <- as.data.frame(t(read.table(paste("../Expression/out_genes/",gene,"/",i,".txt",sep=""),header=T,sep="\t",row.names=1)))
+ temp$type <- as.factor(ifelse(grepl("11",row.names(temp)),"Normal","Tumor"))
+ temp$cancer <- rep(i,nrow(temp))
+ if(ncol(temp)<3 | length(unique(temp$type))<2){
+ if(length(cancer.list) > 1){
+ #showNotification(paste0("WARNING! Project ", i, " does not have normal tissue data! Skipping..."), duration = 8, type = "warning")
+ next
+ }else{
+ #showNotification(paste0("SORRY! Project ", i, " does not have normal tissue data! Choose another project."), duration = 8, type = "error")
+ break
+ }
+
+ }else{
+ colnames(temp) <- c("value","type","cancer")
+ print(i)
+ pval <- c(pval,signif(kruskal.test(value~type,temp)$p.value,2))
+ data <- rbind(data,temp)
+ }
+ count <- count + 1
+ }
+
+ if(nrow(data)==0){
+ return()
+ }else{
+ data$value <- 2^data$value
+ p <- ggplot(data = data, aes(x=type, y=value)) + geom_boxplot(aes(fill=type),outlier.size = 0.2,outlier.alpha=0.8) + scale_y_continuous(limits = c(0, 2000)) +
+ geom_text(data=data.frame(x=1.5,y=1800,labels=pval,cancer=unique(data$cancer)),aes(x,y,label=labels),size=3 , inherit.aes=FALSE) +
+ theme(panel.grid.major = element_blank(), panel.grid.minor = element_blank(),
+ panel.background = element_blank(), axis.line = element_line(colour = "black"))
+ #cat("printing",gene,"\n")
+ print(p + facet_wrap( ~ cancer, scales="free") + ggtitle(gene) + theme(plot.title = element_text(hjust = 0.5)))
+ #incProgress(1/n, detail = paste0("printing plot!"))
+ }
}
+ #SURVIVAL PLOTS
}else if(vars()$operation=="Survival"){
#Define Cancer & Gene
- cat("Survival plot/n")
+ oldw <- getOption("warn")
+ options(warn = -1)
+ cat("Survival plot\n")
cancer <- vars()$cancer
- gene <- vars()$gene
+ gene<-toupper(gsub("\\s", "", as.character(vars()$gene)))
cat(paste0(cancer," ",gene,"\n"))
-
- #Import Expression and Clinical Data
- cat(paste0("going to read expression ",cancer))
- exp <- read.table(paste0("../Expression/",cancer,".txt"),header=T,row.names=1,check.names=F) #Instead of importing entire expression matrix should import single gene.
- # exp <- read.table(paste("Expression/",cancer,".txt",sep=""),header=T,row.names=1,check.names=F)
- cat("going to read clinical data")
- clinical <- read.table(paste("../Clinical/",cancer,".txt",sep=""),header=T,row.names=1,sep="\t")
-
-
- #Process Clinical
- # get the columns that contain data we can use: days to death, new tumor event, last day contact to....
- ind_keep <- grep("days_to_new_tumor_event_after_initial_treatment",colnames(clinical))
-
- # this is a bit tedious, since there are numerous follow ups, let's collapse them together and keep the first value (the higher one) if more than one is available
- new_tum <- as.matrix(clinical[,ind_keep])
- new_tum_collapsed <- c()
- for (i in 1:dim(new_tum)[1]){
- if(sum(is.na(new_tum[i,])) < dim(new_tum)[2]){
- m <- min(new_tum[i,],na.rm=T)
- new_tum_collapsed <- c(new_tum_collapsed,m)
- } else {
- new_tum_collapsed <- c(new_tum_collapsed,"NA")
+ if(!(gene %in% all.genes)){
+ #showNotification(paste0("SORRY! ", gene, " is not a valid gene!"), duration = 8, type = "error")
+ }else{
+ n <- 4
+ #incProgress(1/n, detail = "Getting expression data")
+ #Import Expression and Clinical Data
+ cat(paste0("going to read expression ",cancer,"\n"))
+ if(!file.exists(paste0("../Expression/out_genes/",gene,"/",cancer,".txt"))){
+ cat("File not present\n")
+ if(!dir.exists(paste0("../Expression/out_genes/",gene))){
+ system(paste0("mkdir ../Expression/out_genes/",gene))
+ cat("Made directory\n")
+ }
+ system(paste0("ls ../Expression/*",cancer,"*txt | while read line ; do fname=$(basename $line); head -1 $line > ../Expression/out_genes/",
+ gene,"/","$fname; grep -wi ",gene," $line >> ../Expression/out_genes/",gene,"/","$fname;done"))
+ cat("creating data\n")
+
}
- }
-
- # do the same to death
- ind_keep <- grep("days_to_death",colnames(clinical))
- death <- as.matrix(clinical[,ind_keep])
- death_collapsed <- c()
- for (i in 1:dim(death)[1]){
- if(sum(is.na(death[i,])) < dim(death)[2]){
- m <- max(death[i,],na.rm=T)
- death_collapsed <- c(death_collapsed,m)
- } else {
- death_collapsed <- c(death_collapsed,"NA")
+ exp <- read.table(paste0("../Expression/out_genes/",gene,"/",cancer,".txt"),header=T,row.names=1,check.names=F)
+ #exp <- read.table(paste0("../Expression/",cancer,".txt"),header=T,row.names=1,check.names=F) #Instead of importing entire expression matrix should import single gene.
+ cat("going to read clinical data\n")
+ #incProgress(1/n, detail = "Getting clinical data")
+ clinical <- read.table(paste("../Clinical/",cancer,".txt",sep=""),header=T,row.names=1,sep="\t")
+
+
+ #Process Clinical
+ # get the columns that contain data we can use: days to death, new tumor event, last day contact to....
+ ind_keep <- grep("days_to_new_tumor_event_after_initial_treatment",colnames(clinical))
+
+ # this is a bit tedious, since there are numerous follow ups, let's collapse them together and keep the first value (the higher one) if more than one is available
+ new_tum <- as.matrix(clinical[,ind_keep])
+ new_tum_collapsed <- c()
+ for (i in 1:dim(new_tum)[1]){
+ if(sum(is.na(new_tum[i,])) < dim(new_tum)[2]){
+ m <- min(new_tum[i,],na.rm=T)
+ new_tum_collapsed <- c(new_tum_collapsed,m)
+ } else {
+ new_tum_collapsed <- c(new_tum_collapsed,"NA")
+ }
}
- }
-
- # and days last follow up here we take the most recent which is the max number
- ind_keep <- grep("days_to_last_followup",colnames(clinical))
- fl <- as.matrix(clinical[,ind_keep])
- fl_collapsed <- c()
- for (i in 1:dim(fl)[1]){
- if(sum(is.na(fl[i,])) < dim(fl)[2]){
- m <- max(fl[i,],na.rm=T)
- fl_collapsed <- c(fl_collapsed,m)
- } else {
- fl_collapsed <- c(fl_collapsed,"NA")
+
+ # do the same to death
+ ind_keep <- grep("days_to_death",colnames(clinical))
+ death <- as.matrix(clinical[,ind_keep])
+ death_collapsed <- c()
+ for (i in 1:dim(death)[1]){
+ if(sum(is.na(death[i,])) < dim(death)[2]){
+ m <- max(death[i,],na.rm=T)
+ death_collapsed <- c(death_collapsed,m)
+ } else {
+ death_collapsed <- c(death_collapsed,"NA")
+ }
+ }
+
+ # and days last follow up here we take the most recent which is the max number
+ ind_keep <- grep("days_to_last_followup",colnames(clinical))
+ fl <- as.matrix(clinical[,ind_keep])
+ fl_collapsed <- c()
+ for (i in 1:dim(fl)[1]){
+ if(sum(is.na(fl[i,])) < dim(fl)[2]){
+ m <- max(fl[i,],na.rm=T)
+ fl_collapsed <- c(fl_collapsed,m)
+ } else {
+ fl_collapsed <- c(fl_collapsed,"NA")
+ }
+ }
+
+ # and put everything together
+ all_clin <- data.frame(new_tum_collapsed,death_collapsed,fl_collapsed)
+ colnames(all_clin) <- c("new_tumor_days", "death_days", "followUp_days")
+
+ # create vector with time to new tumor containing data to censor for new_tumor
+ all_clin$new_time <- c()
+ for (i in 1:length(as.numeric(as.character(all_clin$new_tumor_days)))){
+ all_clin$new_time[i] <- ifelse(is.na(as.numeric(as.character(all_clin$new_tumor_days))[i]),
+ as.numeric(as.character(all_clin$followUp_days))[i],as.numeric(as.character(all_clin$new_tumor_days))[i])
+ }
+
+ # create vector time to death containing values to censor for death
+ all_clin$new_death <- c()
+ for (i in 1:length(as.numeric(as.character(all_clin$death_days)))){
+ all_clin$new_death[i] <- ifelse(is.na(as.numeric(as.character(all_clin$death_days))[i]),
+ as.numeric(as.character(all_clin$followUp_days))[i],as.numeric(as.character(all_clin$death_days))[i])
+ }
+
+ all_clin$death_event <- ifelse(clinical$vital_status == "LIVING", 0,1)
+ row.names(all_clin) <- row.names(clinical)
+ colnames(exp) <- gsub("01A","01",colnames(exp))
+ gene.exp <- t(exp[gene,])
+ colnames(gene.exp) <- "gene"
+
+ #Fork for Manual vs Automatic selection
+ if(vars()$operation2 == "Manual"){
+ cutoff <- as.numeric(vars()$cutoff)
+ #Setup Data
+
+ colnames(exp) <- gsub("01A","01",colnames(exp))
+ gene.exp <- t(exp[gene,])
+ colnames(gene.exp) <- "gene"
+ data <- merge(all_clin,gene.exp,by="row.names")
+ data$event_rna <- ifelse(data$gene > quantile(as.numeric(data$gene),1-cutoff),1,0)
+ data <- data[which(data$gene > quantile(as.numeric(data$gene),1-cutoff) | data$gene < quantile(as.numeric(data$gene),cutoff)),]
+ # run survival analysis
+ s <- surv_fit(Surv(as.numeric(as.character(data$new_death)),data$death_event)~event_rna,data)
+ #incProgress(1/n, detail = "Printing plot")
+ p<-ggsurvplot(s,conf.int=F,xlab="Time(days)",pval=T,pval.coord=c(1000,0.3),risk.table=TRUE,legend.title="",legend=c(0.8,0.8),legend.labs = c( paste(gene,"LOW",sep=" "), paste(gene,"HIGH",sep=" ")))
+ print(p+ggtitle(paste(cancer, gene,"cutoff: ", cutoff)))
+ options(warn = oldw)
+ }else{
+ cutoff.vals=c(.10, .15, .20, .25, .30, .35, .40, .45, .50)
+ #incProgress(1/n, detail = "Checking Cutoffs")
+ for(cutoff in cutoff.vals){
+ cat("\tchecking cutoff value:",cutoff,"\n") ###add status update here
+ data <- merge(all_clin,gene.exp,by="row.names")
+ if(is.na(data$gene)[1]){
+ showNotification(paste0("SORRY! No data for gene ", gene,"!"), duration = 8, type = "error")
+ break
+ }
+ data$event_rna <- ifelse(data$gene > quantile(as.numeric(data$gene),1-cutoff),1,0)
+ data <- data[which(data$gene > quantile(as.numeric(data$gene),1-cutoff) | data$gene < quantile(as.numeric(data$gene),cutoff)),]
+ # run survival analysis
+ if(length(unique(data$event_rna)) < 2){
+ next
+ }
+
+ cat("done!\n")
+ if(cutoff == 0.10){
+ cat("first run\n")
+ best.data <- data
+ best.res <- surv_fit(Surv(as.numeric(as.character(best.data$new_death)),best.data$death_event)~event_rna,best.data)
+ p<-ggsurvplot(best.res,conf.int=F,xlab="Time(days)",pval=TRUE,pval.coord=c(1000,0.3),risk.table=TRUE,legend.title="",legend=c(0.8,0.8),
+ legend.labs = c( paste(gene,"LOW",sep=" "), paste(gene,"HIGH",sep=" ")))
+ best.cutoff <- cutoff
+ }else{
+ s <- surv_fit(Surv(as.numeric(as.character(data$new_death)),data$death_event)~event_rna,data)
+ p<-ggsurvplot(s,conf.int=F,xlab="Time(days)",pval=TRUE,pval.coord=c(1000,0.3),risk.table=TRUE,legend.title="",legend=c(0.8,0.8),
+ legend.labs = c( paste(gene,"LOW",sep=" "), paste(gene,"HIGH",sep=" ")))
+ if((as.numeric(surv_pvalue(s)[2]) < as.numeric(surv_pvalue(best.res)[2])) & (p$table$data$n.risk[1] > 10) & (p$table$data$n.risk[6] > 10)){
+ best.data <- data
+ best.res <- surv_fit(Surv(as.numeric(as.character(best.data$new_death)),best.data$death_event)~event_rna,best.data)
+ p<-ggsurvplot(best.res,conf.int=F,xlab="Time(days)",pval=TRUE,pval.coord=c(1000,0.3),risk.table=TRUE,legend.title="",legend=c(0.8,0.8),
+ legend.labs = c( paste(gene,"LOW",sep=" "), paste(gene,"HIGH",sep=" ")))
+ best.cutoff <- cutoff
+ }
+ }
+
+ }
+ #incProgress(1/n, detail = "Printing plot")
+ p <- ggsurvplot(best.res,conf.int=F,xlab="Time(days)",pval=TRUE,pval.coord=c(1000,0.3),risk.table=TRUE,legend.title="",legend=c(0.8,0.8),
+ legend.labs = c( paste(gene,"LOW",sep=" "), paste(gene,"HIGH",sep=" ")))
+ print(p+ggtitle(paste(cancer, "cutoff: ", best.cutoff)))
+
}
}
-
- # and put everything together
- all_clin <- data.frame(new_tum_collapsed,death_collapsed,fl_collapsed)
- colnames(all_clin) <- c("new_tumor_days", "death_days", "followUp_days")
-
- # create vector with time to new tumor containing data to censor for new_tumor
- all_clin$new_time <- c()
- for (i in 1:length(as.numeric(as.character(all_clin$new_tumor_days)))){
- all_clin$new_time[i] <- ifelse(is.na(as.numeric(as.character(all_clin$new_tumor_days))[i]),
- as.numeric(as.character(all_clin$followUp_days))[i],as.numeric(as.character(all_clin$new_tumor_days))[i])
- }
-
- # create vector time to death containing values to censor for death
- all_clin$new_death <- c()
- for (i in 1:length(as.numeric(as.character(all_clin$death_days)))){
- all_clin$new_death[i] <- ifelse(is.na(as.numeric(as.character(all_clin$death_days))[i]),
- as.numeric(as.character(all_clin$followUp_days))[i],as.numeric(as.character(all_clin$death_days))[i])
- }
-
- all_clin$death_event <- ifelse(clinical$vital_status == "LIVING", 0,1)
- row.names(all_clin) <- row.names(clinical)
-
- cutoff <- as.numeric(vars()$cutoff)
- #Setup Data
- ### Deprecated Code ###
- # data <- all_clin[names[names %in% row.names(all_clin)],]#[which(substr(colnames(exp),14,14) == "0"),]
- #all_clin$event_rna <- apply(exp[gene,], 1, function(x) ifelse(abs(x) > median(as.numeric(exp[gene,])),1,0))
- # gene.exp <- apply(gene.exp,2,function(x) ifelse(x > quantile(as.numeric(x),1-cutoff),1,0))
- # gene.exp <- t(as.data.frame(sapply(by(gene.exp,rownames(gene.exp),colSums),identity)))
- colnames(exp) <- gsub("01A","01",colnames(exp))
- gene.exp <- t(exp[gene,])
- colnames(gene.exp) <- "gene"
- data <- merge(all_clin,gene.exp,by="row.names")
- data$event_rna <- ifelse(data$gene > quantile(as.numeric(data$gene),1-cutoff),1,0)
- data <- data[which(data$gene > quantile(as.numeric(data$gene),1-cutoff) | data$gene < quantile(as.numeric(data$gene),cutoff)),]
- # run survival analysis
- s <- surv_fit(Surv(as.numeric(as.character(data$new_death)),data$death_event)~event_rna,data)
- p<-ggsurvplot(s,conf.int=F,xlab="Time(days)",pval=T,pval.coord=c(1000,0.3),risk.table=TRUE,legend.title="",legend=c(0.8,0.8),legend.labs = c( paste(gene,"LOW",sep=" "), paste(gene,"HIGH",sep=" ")))
- print(p+ggtitle(paste(cancer, gene,"cutoff: ", cutoff)))
}
-
- })
+ }
+
+ output$downloadplot <- downloadHandler(
+ filename = function() { paste0("plot", '.pdf') },
+ content = function(file) {
+ #ggsave(file = file, plot = plotInput(), device = "pdf")
+ pdf(file)
+ plotInput()
+ dev.off()
+ }
+ )
}
diff --git a/scripts/tcga_genes.txt b/scripts/tcga_genes.txt
new file mode 100755
index 0000000000000000000000000000000000000000..8645a50825cbb36c227f288578350c3be818118c
--- /dev/null
+++ b/scripts/tcga_genes.txt
@@ -0,0 +1,20530 @@
+?|100130426
+?|100133144
+?|100134869
+?|10357
+?|10431
+?|136542
+?|155060
+?|26823
+?|280660
+?|317712
+?|340602
+?|388795
+?|390284
+?|391343
+?|391714
+?|404770
+?|441362
+?|442388
+?|553137
+?|57714
+?|645851
+?|652919
+?|653553
+?|728045
+?|728603
+?|728788
+?|729884
+?|8225
+?|90288
+A1BG
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+ALOX5
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+ALPK1
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+AMPD1
+AMPD2
+AMPD3
+AMPH
+AMT
+AMTN
+AMY1A
+AMY2A
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diff --git a/scripts/ui.R b/scripts/ui.R
old mode 100755
new mode 100644
index c7b5a3d434fbc67273d81d409cfa8069739eaa50..4db5af678a6c0d4136ec354f341ee1deff51de8b
--- a/scripts/ui.R
+++ b/scripts/ui.R
@@ -1,41 +1,36 @@
shinyUI(
- pageWithSidebar(
- headerPanel("TGCA Analysis"),
- sidebarPanel(
- selectInput("operation","Select Plot Type",choices = c("Pancan","Survival")),
- conditionalPanel(condition = "input.operation=='Pancan'",
- selectInput("cancerType","Select one or more cancer types",
- choices = substr(list.files("../Expression/",pattern=".txt"),1,
- nchar(list.files("../Expression/",pattern=".txt"))-4),
- multiple = TRUE),
- textInput("gene","Please input one gene of interest",placeholder = "Gene name ie 'TRIM21'")
- ),
- conditionalPanel(condition="input.operation=='Survival'",
- selectInput("cancerType2","Select a cancer type",
- choices = substr(list.files("../Expression/",pattern=".txt"),1,
- nchar(list.files("../Expression/",pattern=".txt"))-4)),
- textInput("gene2","Please input one gene of interest",placeholder = "Gene name ie 'TRIM21'",value="TRIM21"),
- sliderInput("cut.off","Select a cutoff value",min = .10,max=.50,step = .05,value = .25)
+ fluidPage(
+ headerPanel("TCGA Analysis"),
+ sidebarLayout(
+ sidebarPanel(
+ selectInput("operation","Select Plot Type",choices = c("Boxplot","Survival")),
+ conditionalPanel(condition = "input.operation=='Boxplot'",
+ selectInput("cancerType","Select one or more cancer types",
+ choices = substr(list.files("../Expression/",pattern=".txt"),1,
+ nchar(list.files("../Expression/",pattern=".txt"))-4),
+ multiple = TRUE),
+ textInput("gene","Please input one gene of interest",placeholder = "Gene name ie TRIM21")
+ ),
+ conditionalPanel(condition="input.operation=='Survival'",
+ selectInput("cancerType2","Select a cancer type",
+ choices = substr(list.files("../Expression/",pattern=".txt"),1,
+ nchar(list.files("../Expression/",pattern=".txt"))-4)),
+ textInput("gene2","Please input one gene of interest",placeholder = "Gene name ie BRCA1"),
+ selectInput("operation2","Select automatic or manual cutoff", choices = c("Automatic", "Manual"))
+
+ ),
+ conditionalPanel(condition="input.operation2=='Manual' & input.operation=='Survival'",
+ sliderInput("cut.off","Select a cutoff value",min = .10,max=.50,step = .05,value = .25)
+ ),
+ actionButton("go","GO")
+
),
- actionButton("go","GO")
- #conditionalPanel(condition = "input.operation=='Pancan'"
-
- # )
- #selectInput("Distribution", "Select dist type",
- # choices=c("normal","expo")),
- #sliderInput("sampleSize","Select sample size: ",
- # min=100,max=5000,value=1000,step=100),
- #conditionalPanel(condition = "input.Distribution=='normal'",
- # textInput("Mean","Plase Select the mean",10),
- # textInput("sd","Please Select Standard Deviation",3)),
- #conditionalPanel(condition="input.Distribution == 'expo'",
- # textInput("lambda","Pleas select Expo Lambda",1)
- #)
- ),
- mainPanel(
- plotOutput("myPlot")
+ mainPanel(
+ plotOutput("myPlot"),
+ downloadButton('downloadplot',"Download Figure")
+ )
+
)
-
)
)