R/drugGDSC.R
In seanchen607/deplink: Compares the genetic/epigenetic features between cancer cell lines with different dependencies of a gene set (signature)
Defines functions
drugGDSC
Documented in
drugGDSC
##' 'drugGDSC' compares the drug sensitivity (GDSC dataset) between cancer cell lines with highest and lowest dependencies of a gene set (signature).
##'
##'
##' @title drugGDSC
##' @param signature.name Names of a signature (format: character)
##' @param signature Gene names of a signature (format: vector)
##' @param cutoff.freq Cutoff for frequency of cancer cell lines for each cancer type, default 10
##' @param cutoff.percentile Cutoff for percentile of cancer cell lines with highest/lowest dependency, default 0.2
##' @param cutoff.pvalue Cutoff for p-value of the T-test results, default 0.05
##' @param cutoff.diff Cutoff for difference of the T-test results, default 0.5
##' @return plot
##' @importFrom stats complete.cases
##' @importFrom wesanderson wes_palette
##' @importFrom cowplot plot_grid
##' @importFrom purrr map
##' @importFrom ggrepel geom_label_repel
##' @import data.table ggpubr ggplot2
##' @export
##' @author Xiao Chen
##' @references 1. X Chen, J McGuire, F Zhu, X Xu, Y Li, D Karagiannis, R Dalla-Favera, A Ciccia, J Amengual, C Lu (2020).
##' Harnessing genetic dependency correlation network to reveal chromatin vulnerability in cancer.
##' In preparation.
##' @examples
##' source(system.file("script", "load_libs.R", package = "deplink"))
##' signature.name = "9-1-1"
##' signature = c("RAD9A", "RAD1", "HUS1", "RAD17")
##' drugGDSC(signature.name, signature)
## Main
drugGDSC <- function(signature.name,
signature,
cutoff.freq = 10,
cutoff.percentile = 0.2,
cutoff.pvalue = 0.05,
cutoff.diff = 0.5
) {
# Primary.Disease.freq = table(dep.t.signature.meta.order$disease)
Primary.Disease.freq = table(dep.t.meta$tcga_code)
Primary.Disease.freq.cutoff = Primary.Disease.freq[Primary.Disease.freq >= cutoff.freq]
TCGA.tumor.target = TCGA.tumor[TCGA.tumor$tcga_code %in% names(Primary.Disease.freq.cutoff),,drop=FALSE]
head(TCGA.tumor.target)
dim(TCGA.tumor.target)
# 1047 1
dep.t = dep.t[rownames(dep.t) %in% rownames(TCGA.tumor.target),,drop=FALSE]
head(dep.t)
dim(dep.t)
# 458 18333
dep.t.signature = dep.t[,colnames(dep.t) %in% signature, drop=FALSE]
dep.t.signature$signature.score = rowMeans(dep.t.signature)*(-1)
dep.t.signature = dep.t.signature[order(dep.t.signature$signature.score, decreasing=TRUE),]
head(dep.t.signature)
dim(dep.t.signature)
# 558 5
dep.t.signature.high = dep.t.signature[1:ceiling(nrow(dep.t.signature)*cutoff.percentile),,drop=FALSE]
head(dep.t.signature.high)
dim(dep.t.signature.high)
# 56 12
dep.t.signature.low = dep.t.signature[(nrow(dep.t.signature)-ceiling(nrow(dep.t.signature)*cutoff.percentile) + 1):nrow(dep.t.signature),,drop=FALSE]
head(dep.t.signature.low)
dim(dep.t.signature.low)
# 56 12
# write.csv(dep.t.signature, paste0("dep_", signature.name, "_score.csv"))
# write.csv(dep.t.signature.high, paste0("dep_", signature.name, "_score.high", cutoff.percentile, ".csv"))
# write.csv(dep.t.signature.low, paste0("dep_", signature.name, "_score.low", cutoff.percentile, ".csv"))
#############################################
# Drug sensitivity - GDSC
drug.share = drug[rownames(drug) %in% rownames(dep.t),,drop=FALSE]
head(drug.share)
dim(drug.share)
# 327 266
drug.share.signature.high = drug.share[rownames(drug.share) %in% rownames(dep.t.signature.high),,drop=FALSE]
drug.share.signature.high$signature = paste0(signature.name, ".dep.high")
head(drug.share.signature.high)
dim(drug.share.signature.high)
# 27 267
drug.share.signature.low = drug.share[rownames(drug.share) %in% rownames(dep.t.signature.low),,drop=FALSE]
drug.share.signature.low$signature = paste0(signature.name, ".dep.low")
head(drug.share.signature.low)
dim(drug.share.signature.low)
# 33 267
drug.share.signature.mid = drug.share[!rownames(drug.share) %in% c(rownames(dep.t.signature.high), rownames(dep.t.signature.low)),,drop=FALSE]
drug.share.signature.mid$signature = paste0(signature.name, ".dep.mid")
head(drug.share.signature.mid)
dim(drug.share.signature.mid)
# 267 267
drug.share.signature = rbind(drug.share.signature.high, drug.share.signature.mid, drug.share.signature.low)
head(drug.share.signature)
dim(drug.share.signature)
# 327 267
# write.csv(drug.share.signature, paste0("drug.GDSC/dep_", signature.name, "_hml", cutoff.percentile, "_drug.csv"), quote=FALSE)
drug.high = drug.share.signature[drug.share.signature$signature %like% "high",,drop=FALSE]
head(drug.high)
dim(drug.high)
# 27 267
drug.mid = drug.share.signature[drug.share.signature$signature %like% "mid",,drop=FALSE]
drug.low = drug.share.signature[drug.share.signature$signature %like% "low",,drop=FALSE]
# signature.high
drug.high.p = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) ifelse(length(x[1:nrow(drug.high)][!is.na(x[1:nrow(drug.high)])])>1, signif(t.test(x[1:nrow(drug.high)], x[(nrow(drug.high)+1):nrow(drug.share.signature)])$p.value,5), NA))
head(drug.high.p)
length(drug.high.p)
# 266
drug.high.q = signif(p.adjust(drug.high.p, "BH"),5)
head(drug.high.q)
length(drug.high.q)
# 266
drug.high.mean1 = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) signif(mean(na.omit(x[1:nrow(drug.high)])), 5))
drug.high.mean2 = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) signif(mean(na.omit(x[(nrow(drug.high)+1):nrow(drug.share.signature)])), 5))
drug.high.diff = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) signif(mean(na.omit(x[1:nrow(drug.high)])) - mean(na.omit(x[(nrow(drug.high)+1):nrow(drug.share.signature)])), 5))
head(drug.high.diff)
length(drug.high.diff)
# 266
drug.high.deg = data.frame(drug.high.mean1, drug.high.mean2, drug.high.diff, drug.high.p, drug.high.q, row.names=names(drug.high.diff))
colnames(drug.high.deg) = c("drug.high", "drug.other", "diff.high2other", "pvalue", "qvalue")
head(drug.high.deg)
dim(drug.high.deg)
# 266 5
drug.high.deg = merge(drug.high.deg, drug.meta, by="row.names", all.x=TRUE)
rownames(drug.high.deg) = drug.high.deg[,1]
drug.high.deg = drug.high.deg[,-1]
head(drug.high.deg)
dim(drug.high.deg)
# 266 9
# write.csv(drug.high.deg, paste0("drug.GDSC/dep_", signature.name, "_hml", cutoff.percentile, "_drug.high.deg.csv"), quote=TRUE)
# signature.low
drug.low.p = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) ifelse(length(x[1:(nrow(drug.share.signature)-nrow(drug.low))][!is.na(x[1:(nrow(drug.share.signature)-nrow(drug.low))])])>1, signif(t.test(x[1:(nrow(drug.share.signature)-nrow(drug.low))], x[(nrow(drug.share.signature)-nrow(drug.low)+1):nrow(drug.share.signature)])$p.value,5), NA))
head(drug.low.p)
length(drug.low.p)
# 266
drug.low.q = signif(p.adjust(drug.low.p, "BH"),5)
head(drug.low.q)
length(drug.low.q)
# 266
drug.low.mean1 = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) signif(mean(na.omit(x[(nrow(drug.share.signature)-nrow(drug.low)):(nrow(drug.share.signature)-1)])), 5))
drug.low.mean2 = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) signif(mean(na.omit(x[1:(nrow(drug.share.signature)-nrow(drug.low)-1)])), 5))
drug.low.diff = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) signif(mean(na.omit(x[(nrow(drug.share.signature)-nrow(drug.low)+1):nrow(drug.share.signature)])) - mean(na.omit(x[1:(nrow(drug.share.signature)-nrow(drug.low))])), 5))
head(drug.low.diff)
length(drug.low.diff)
# 266
drug.low.deg = data.frame(drug.low.mean1, drug.low.mean2, drug.low.diff, drug.low.p, drug.low.q, row.names=names(drug.low.diff))
colnames(drug.low.deg) = c("drug.low", "drug.other", "diff.low2other", "pvalue", "qvalue")
head(drug.low.deg)
dim(drug.low.deg)
# 266 5
drug.low.deg = merge(drug.low.deg, drug.meta, by="row.names", all.x=TRUE)
rownames(drug.low.deg) = drug.low.deg[,1]
drug.low.deg = drug.low.deg[,-1]
head(drug.low.deg)
dim(drug.low.deg)
# 266 9
# write.csv(drug.low.deg, paste0("drug.GDSC/dep_", signature.name, "_hml", cutoff.percentile, "_drug.low.deg.csv"), quote=TRUE)
drug.high.deg$DRUG_NAME = gsub(" \\(.+\\)", "", drug.high.deg$DRUG_NAME)
drug.low.deg$DRUG_NAME = gsub(" \\(.+\\)", "", drug.low.deg$DRUG_NAME)
# cutoff.pvalue = 0.05
# cutoff.diff = 0.6
set.seed(42)
p1 <- ggplot(data = drug.high.deg, mapping = aes(x = diff.high2other, y = (-1)*log(pvalue, 10))) +
geom_point(size=1, color= ifelse(drug.high.deg$pvalue < cutoff.pvalue & drug.high.deg$diff.high2other > cutoff.diff, "blue", ifelse(drug.high.deg$pvalue < cutoff.pvalue & drug.high.deg$diff.high2other < cutoff.diff*(-1), "red", "grey60")))+
# xlim(-1.5,1.5) +
# ylim(0,4) +
geom_hline(yintercept = (-1)*log(cutoff.pvalue, 10), linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = (-1)*cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
annotate("text", x=min(na.omit(drug.high.deg$diff.high2other), na.omit(drug.high.deg$diff.low2other)), y=max(na.omit((-1)*log(drug.high.deg$pvalue, 10)), na.omit((-1)*log(drug.low.deg$pvalue, 10)))*1.1, parse=FALSE, label = paste0("Signature.high cell lines: ", nrow(drug.share.signature.high)), color = "red", hjust = 0) +
geom_label_repel(aes(label=ifelse(drug.high.deg$pvalue < cutoff.pvalue & abs(drug.high.deg$diff.high2other) > cutoff.diff, as.character(drug.high.deg$DRUG_NAME), "")), size = 2, color = ifelse(drug.high.deg$diff.high2other > 0, "blue", "red"), segment.size=0.2) +
labs(x="Sensitivity difference", y="-log10(p value)", title=paste0("Signature [", signature.name, "] High vs. others"))
p1 <- p1 + theme_classic() + rremove("legend")
# p1
p2 <- ggplot(data = drug.low.deg, mapping = aes(x = diff.low2other, y = (-1)*log(pvalue, 10))) +
geom_point(size=1, color= ifelse(drug.low.deg$pvalue < cutoff.pvalue & drug.low.deg$diff.low2other > cutoff.diff, "blue", ifelse(drug.low.deg$pvalue < cutoff.pvalue & drug.low.deg$diff.low2other < cutoff.diff*(-1), "red", "grey60")))+
# xlim(-1.5,1.5) +
# ylim(0,4) +
geom_hline(yintercept = (-1)*log(cutoff.pvalue, 10), linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = (-1)*cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
annotate("text", x=min(na.omit(drug.high.deg$diff.high2other), na.omit(drug.high.deg$diff.low2other)), y=max(na.omit((-1)*log(drug.high.deg$pvalue, 10)), na.omit((-1)*log(drug.low.deg$pvalue, 10)))*1.1, parse=FALSE, label = paste0("Signature.low cell lines: ", nrow(drug.share.signature.low)), color = "red", hjust = 0) +
geom_label_repel(aes(label=ifelse(drug.low.deg$pvalue < cutoff.pvalue & abs(drug.low.deg$diff.low2other) > cutoff.diff, as.character(drug.low.deg$DRUG_NAME), "")), size = 2, color = ifelse(drug.low.deg$diff.low2other > 0, "blue", "red"), segment.size=0.2) +
labs(x="Sensitivity difference", y="-log10(p value)", title=paste0("Signature [", signature.name, "] Low vs. others"))
p2 <- p2 + theme_classic() + rremove("legend")
# p2
p3 <- ggplot(data = drug.high.deg, mapping = aes(x = diff.high2other, y = (-1)*log(pvalue, 10))) +
geom_point(size=1, color= ifelse(drug.high.deg$pvalue < cutoff.pvalue & drug.high.deg$diff.high2other > cutoff.diff, "blue", ifelse(drug.high.deg$pvalue < cutoff.pvalue & drug.high.deg$diff.high2other < cutoff.diff*(-1), "red", "grey60")))+
# xlim(-1.5,1.5) +
# ylim(0,4) +
geom_hline(yintercept = (-1)*log(cutoff.pvalue, 10), linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = (-1)*cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
annotate("text", x=min(na.omit(drug.high.deg$diff.high2other), na.omit(drug.high.deg$diff.low2other)), y=max(na.omit((-1)*log(drug.high.deg$pvalue, 10)), na.omit((-1)*log(drug.low.deg$pvalue, 10)))*1.1, parse=FALSE, label = paste0("Signature.high cell lines: ", nrow(drug.share.signature.high)), color = "red", hjust = 0) +
geom_label_repel(aes(label=ifelse(drug.high.deg$pvalue < cutoff.pvalue & abs(drug.high.deg$diff.high2other) > cutoff.diff, as.character(drug.high.deg$TARGET_PATHWAY), "")), size = 2, color = ifelse(drug.high.deg$diff.high2other > 0, "blue", "red"), segment.size=0.2) +
labs(x="Sensitivity difference", y="-log10(p value)", title=paste0("Signature [", signature.name, "] High vs. others"))
p3 <- p3 + theme_classic() + rremove("legend")
# p3
p4 <- ggplot(data = drug.low.deg, mapping = aes(x = diff.low2other, y = (-1)*log(pvalue, 10))) +
geom_point(size=1, color= ifelse(drug.low.deg$pvalue < cutoff.pvalue & drug.low.deg$diff.low2other > cutoff.diff, "blue", ifelse(drug.low.deg$pvalue < cutoff.pvalue & drug.low.deg$diff.low2other < cutoff.diff*(-1), "red", "grey60")))+
# xlim(-1.5,1.5) +
# ylim(0,4) +
geom_hline(yintercept = (-1)*log(cutoff.pvalue, 10), linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = (-1)*cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
annotate("text", x=min(na.omit(drug.high.deg$diff.high2other), na.omit(drug.high.deg$diff.low2other)), y=max(na.omit((-1)*log(drug.high.deg$pvalue, 10)), na.omit((-1)*log(drug.low.deg$pvalue, 10)))*1.1, parse=FALSE, label = paste0("Signature.low cell lines: ", nrow(drug.share.signature.low)), color = "red", hjust = 0) +
geom_label_repel(aes(label=ifelse(drug.low.deg$pvalue < cutoff.pvalue & abs(drug.low.deg$diff.low2other) > cutoff.diff, as.character(drug.low.deg$TARGET_PATHWAY), "")), size = 2, color = ifelse(drug.low.deg$diff.low2other > 0, "blue", "red"), segment.size=0.2) +
labs(x="Sensitivity difference", y="-log10(p value)", title=paste0("Signature [", signature.name, "] Low vs. others"))
p4 <- p4 + theme_classic() + rremove("legend")
# p4
# Arranging the plot using cowplot
p = suppressWarnings(plot_grid(p1, p2, p3, p4, ncol = 2, align = "hv", rel_widths = c(1,1), rel_heights = c(1,1)))
# p <- ggplotGrob(p)
return(p)
}
seanchen607/deplink documentation built on Nov. 18, 2020, 11:15 a.m.
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Defines functions drugGDSC
Documented in drugGDSC
##' 'drugGDSC' compares the drug sensitivity (GDSC dataset) between cancer cell lines with highest and lowest dependencies of a gene set (signature).
##'
##'
##' @title drugGDSC
##' @param signature.name Names of a signature (format: character)
##' @param signature Gene names of a signature (format: vector)
##' @param cutoff.freq Cutoff for frequency of cancer cell lines for each cancer type, default 10
##' @param cutoff.percentile Cutoff for percentile of cancer cell lines with highest/lowest dependency, default 0.2
##' @param cutoff.pvalue Cutoff for p-value of the T-test results, default 0.05
##' @param cutoff.diff Cutoff for difference of the T-test results, default 0.5
##' @return plot
##' @importFrom stats complete.cases
##' @importFrom wesanderson wes_palette
##' @importFrom cowplot plot_grid
##' @importFrom purrr map
##' @importFrom ggrepel geom_label_repel
##' @import data.table ggpubr ggplot2
##' @export
##' @author Xiao Chen
##' @references 1. X Chen, J McGuire, F Zhu, X Xu, Y Li, D Karagiannis, R Dalla-Favera, A Ciccia, J Amengual, C Lu (2020).
##' Harnessing genetic dependency correlation network to reveal chromatin vulnerability in cancer.
##' In preparation.
##' @examples
##' source(system.file("script", "load_libs.R", package = "deplink"))
##' signature.name = "9-1-1"
##' signature = c("RAD9A", "RAD1", "HUS1", "RAD17")
##' drugGDSC(signature.name, signature)
## Main
drugGDSC <- function(signature.name,
signature,
cutoff.freq = 10,
cutoff.percentile = 0.2,
cutoff.pvalue = 0.05,
cutoff.diff = 0.5
) {
# Primary.Disease.freq = table(dep.t.signature.meta.order$disease)
Primary.Disease.freq = table(dep.t.meta$tcga_code)
Primary.Disease.freq.cutoff = Primary.Disease.freq[Primary.Disease.freq >= cutoff.freq]
TCGA.tumor.target = TCGA.tumor[TCGA.tumor$tcga_code %in% names(Primary.Disease.freq.cutoff),,drop=FALSE]
head(TCGA.tumor.target)
dim(TCGA.tumor.target)
# 1047 1
dep.t = dep.t[rownames(dep.t) %in% rownames(TCGA.tumor.target),,drop=FALSE]
head(dep.t)
dim(dep.t)
# 458 18333
dep.t.signature = dep.t[,colnames(dep.t) %in% signature, drop=FALSE]
dep.t.signature$signature.score = rowMeans(dep.t.signature)*(-1)
dep.t.signature = dep.t.signature[order(dep.t.signature$signature.score, decreasing=TRUE),]
head(dep.t.signature)
dim(dep.t.signature)
# 558 5
dep.t.signature.high = dep.t.signature[1:ceiling(nrow(dep.t.signature)*cutoff.percentile),,drop=FALSE]
head(dep.t.signature.high)
dim(dep.t.signature.high)
# 56 12
dep.t.signature.low = dep.t.signature[(nrow(dep.t.signature)-ceiling(nrow(dep.t.signature)*cutoff.percentile) + 1):nrow(dep.t.signature),,drop=FALSE]
head(dep.t.signature.low)
dim(dep.t.signature.low)
# 56 12
# write.csv(dep.t.signature, paste0("dep_", signature.name, "_score.csv"))
# write.csv(dep.t.signature.high, paste0("dep_", signature.name, "_score.high", cutoff.percentile, ".csv"))
# write.csv(dep.t.signature.low, paste0("dep_", signature.name, "_score.low", cutoff.percentile, ".csv"))
#############################################
# Drug sensitivity - GDSC
drug.share = drug[rownames(drug) %in% rownames(dep.t),,drop=FALSE]
head(drug.share)
dim(drug.share)
# 327 266
drug.share.signature.high = drug.share[rownames(drug.share) %in% rownames(dep.t.signature.high),,drop=FALSE]
drug.share.signature.high$signature = paste0(signature.name, ".dep.high")
head(drug.share.signature.high)
dim(drug.share.signature.high)
# 27 267
drug.share.signature.low = drug.share[rownames(drug.share) %in% rownames(dep.t.signature.low),,drop=FALSE]
drug.share.signature.low$signature = paste0(signature.name, ".dep.low")
head(drug.share.signature.low)
dim(drug.share.signature.low)
# 33 267
drug.share.signature.mid = drug.share[!rownames(drug.share) %in% c(rownames(dep.t.signature.high), rownames(dep.t.signature.low)),,drop=FALSE]
drug.share.signature.mid$signature = paste0(signature.name, ".dep.mid")
head(drug.share.signature.mid)
dim(drug.share.signature.mid)
# 267 267
drug.share.signature = rbind(drug.share.signature.high, drug.share.signature.mid, drug.share.signature.low)
head(drug.share.signature)
dim(drug.share.signature)
# 327 267
# write.csv(drug.share.signature, paste0("drug.GDSC/dep_", signature.name, "_hml", cutoff.percentile, "_drug.csv"), quote=FALSE)
drug.high = drug.share.signature[drug.share.signature$signature %like% "high",,drop=FALSE]
head(drug.high)
dim(drug.high)
# 27 267
drug.mid = drug.share.signature[drug.share.signature$signature %like% "mid",,drop=FALSE]
drug.low = drug.share.signature[drug.share.signature$signature %like% "low",,drop=FALSE]
# signature.high
drug.high.p = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) ifelse(length(x[1:nrow(drug.high)][!is.na(x[1:nrow(drug.high)])])>1, signif(t.test(x[1:nrow(drug.high)], x[(nrow(drug.high)+1):nrow(drug.share.signature)])$p.value,5), NA))
head(drug.high.p)
length(drug.high.p)
# 266
drug.high.q = signif(p.adjust(drug.high.p, "BH"),5)
head(drug.high.q)
length(drug.high.q)
# 266
drug.high.mean1 = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) signif(mean(na.omit(x[1:nrow(drug.high)])), 5))
drug.high.mean2 = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) signif(mean(na.omit(x[(nrow(drug.high)+1):nrow(drug.share.signature)])), 5))
drug.high.diff = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) signif(mean(na.omit(x[1:nrow(drug.high)])) - mean(na.omit(x[(nrow(drug.high)+1):nrow(drug.share.signature)])), 5))
head(drug.high.diff)
length(drug.high.diff)
# 266
drug.high.deg = data.frame(drug.high.mean1, drug.high.mean2, drug.high.diff, drug.high.p, drug.high.q, row.names=names(drug.high.diff))
colnames(drug.high.deg) = c("drug.high", "drug.other", "diff.high2other", "pvalue", "qvalue")
head(drug.high.deg)
dim(drug.high.deg)
# 266 5
drug.high.deg = merge(drug.high.deg, drug.meta, by="row.names", all.x=TRUE)
rownames(drug.high.deg) = drug.high.deg[,1]
drug.high.deg = drug.high.deg[,-1]
head(drug.high.deg)
dim(drug.high.deg)
# 266 9
# write.csv(drug.high.deg, paste0("drug.GDSC/dep_", signature.name, "_hml", cutoff.percentile, "_drug.high.deg.csv"), quote=TRUE)
# signature.low
drug.low.p = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) ifelse(length(x[1:(nrow(drug.share.signature)-nrow(drug.low))][!is.na(x[1:(nrow(drug.share.signature)-nrow(drug.low))])])>1, signif(t.test(x[1:(nrow(drug.share.signature)-nrow(drug.low))], x[(nrow(drug.share.signature)-nrow(drug.low)+1):nrow(drug.share.signature)])$p.value,5), NA))
head(drug.low.p)
length(drug.low.p)
# 266
drug.low.q = signif(p.adjust(drug.low.p, "BH"),5)
head(drug.low.q)
length(drug.low.q)
# 266
drug.low.mean1 = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) signif(mean(na.omit(x[(nrow(drug.share.signature)-nrow(drug.low)):(nrow(drug.share.signature)-1)])), 5))
drug.low.mean2 = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) signif(mean(na.omit(x[1:(nrow(drug.share.signature)-nrow(drug.low)-1)])), 5))
drug.low.diff = apply(drug.share.signature[1:(ncol(drug.share.signature)-1)], 2, function(x) signif(mean(na.omit(x[(nrow(drug.share.signature)-nrow(drug.low)+1):nrow(drug.share.signature)])) - mean(na.omit(x[1:(nrow(drug.share.signature)-nrow(drug.low))])), 5))
head(drug.low.diff)
length(drug.low.diff)
# 266
drug.low.deg = data.frame(drug.low.mean1, drug.low.mean2, drug.low.diff, drug.low.p, drug.low.q, row.names=names(drug.low.diff))
colnames(drug.low.deg) = c("drug.low", "drug.other", "diff.low2other", "pvalue", "qvalue")
head(drug.low.deg)
dim(drug.low.deg)
# 266 5
drug.low.deg = merge(drug.low.deg, drug.meta, by="row.names", all.x=TRUE)
rownames(drug.low.deg) = drug.low.deg[,1]
drug.low.deg = drug.low.deg[,-1]
head(drug.low.deg)
dim(drug.low.deg)
# 266 9
# write.csv(drug.low.deg, paste0("drug.GDSC/dep_", signature.name, "_hml", cutoff.percentile, "_drug.low.deg.csv"), quote=TRUE)
drug.high.deg$DRUG_NAME = gsub(" \\(.+\\)", "", drug.high.deg$DRUG_NAME)
drug.low.deg$DRUG_NAME = gsub(" \\(.+\\)", "", drug.low.deg$DRUG_NAME)
# cutoff.pvalue = 0.05
# cutoff.diff = 0.6
set.seed(42)
p1 <- ggplot(data = drug.high.deg, mapping = aes(x = diff.high2other, y = (-1)*log(pvalue, 10))) +
geom_point(size=1, color= ifelse(drug.high.deg$pvalue < cutoff.pvalue & drug.high.deg$diff.high2other > cutoff.diff, "blue", ifelse(drug.high.deg$pvalue < cutoff.pvalue & drug.high.deg$diff.high2other < cutoff.diff*(-1), "red", "grey60")))+
# xlim(-1.5,1.5) +
# ylim(0,4) +
geom_hline(yintercept = (-1)*log(cutoff.pvalue, 10), linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = (-1)*cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
annotate("text", x=min(na.omit(drug.high.deg$diff.high2other), na.omit(drug.high.deg$diff.low2other)), y=max(na.omit((-1)*log(drug.high.deg$pvalue, 10)), na.omit((-1)*log(drug.low.deg$pvalue, 10)))*1.1, parse=FALSE, label = paste0("Signature.high cell lines: ", nrow(drug.share.signature.high)), color = "red", hjust = 0) +
geom_label_repel(aes(label=ifelse(drug.high.deg$pvalue < cutoff.pvalue & abs(drug.high.deg$diff.high2other) > cutoff.diff, as.character(drug.high.deg$DRUG_NAME), "")), size = 2, color = ifelse(drug.high.deg$diff.high2other > 0, "blue", "red"), segment.size=0.2) +
labs(x="Sensitivity difference", y="-log10(p value)", title=paste0("Signature [", signature.name, "] High vs. others"))
p1 <- p1 + theme_classic() + rremove("legend")
# p1
p2 <- ggplot(data = drug.low.deg, mapping = aes(x = diff.low2other, y = (-1)*log(pvalue, 10))) +
geom_point(size=1, color= ifelse(drug.low.deg$pvalue < cutoff.pvalue & drug.low.deg$diff.low2other > cutoff.diff, "blue", ifelse(drug.low.deg$pvalue < cutoff.pvalue & drug.low.deg$diff.low2other < cutoff.diff*(-1), "red", "grey60")))+
# xlim(-1.5,1.5) +
# ylim(0,4) +
geom_hline(yintercept = (-1)*log(cutoff.pvalue, 10), linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = (-1)*cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
annotate("text", x=min(na.omit(drug.high.deg$diff.high2other), na.omit(drug.high.deg$diff.low2other)), y=max(na.omit((-1)*log(drug.high.deg$pvalue, 10)), na.omit((-1)*log(drug.low.deg$pvalue, 10)))*1.1, parse=FALSE, label = paste0("Signature.low cell lines: ", nrow(drug.share.signature.low)), color = "red", hjust = 0) +
geom_label_repel(aes(label=ifelse(drug.low.deg$pvalue < cutoff.pvalue & abs(drug.low.deg$diff.low2other) > cutoff.diff, as.character(drug.low.deg$DRUG_NAME), "")), size = 2, color = ifelse(drug.low.deg$diff.low2other > 0, "blue", "red"), segment.size=0.2) +
labs(x="Sensitivity difference", y="-log10(p value)", title=paste0("Signature [", signature.name, "] Low vs. others"))
p2 <- p2 + theme_classic() + rremove("legend")
# p2
p3 <- ggplot(data = drug.high.deg, mapping = aes(x = diff.high2other, y = (-1)*log(pvalue, 10))) +
geom_point(size=1, color= ifelse(drug.high.deg$pvalue < cutoff.pvalue & drug.high.deg$diff.high2other > cutoff.diff, "blue", ifelse(drug.high.deg$pvalue < cutoff.pvalue & drug.high.deg$diff.high2other < cutoff.diff*(-1), "red", "grey60")))+
# xlim(-1.5,1.5) +
# ylim(0,4) +
geom_hline(yintercept = (-1)*log(cutoff.pvalue, 10), linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = (-1)*cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
annotate("text", x=min(na.omit(drug.high.deg$diff.high2other), na.omit(drug.high.deg$diff.low2other)), y=max(na.omit((-1)*log(drug.high.deg$pvalue, 10)), na.omit((-1)*log(drug.low.deg$pvalue, 10)))*1.1, parse=FALSE, label = paste0("Signature.high cell lines: ", nrow(drug.share.signature.high)), color = "red", hjust = 0) +
geom_label_repel(aes(label=ifelse(drug.high.deg$pvalue < cutoff.pvalue & abs(drug.high.deg$diff.high2other) > cutoff.diff, as.character(drug.high.deg$TARGET_PATHWAY), "")), size = 2, color = ifelse(drug.high.deg$diff.high2other > 0, "blue", "red"), segment.size=0.2) +
labs(x="Sensitivity difference", y="-log10(p value)", title=paste0("Signature [", signature.name, "] High vs. others"))
p3 <- p3 + theme_classic() + rremove("legend")
# p3
p4 <- ggplot(data = drug.low.deg, mapping = aes(x = diff.low2other, y = (-1)*log(pvalue, 10))) +
geom_point(size=1, color= ifelse(drug.low.deg$pvalue < cutoff.pvalue & drug.low.deg$diff.low2other > cutoff.diff, "blue", ifelse(drug.low.deg$pvalue < cutoff.pvalue & drug.low.deg$diff.low2other < cutoff.diff*(-1), "red", "grey60")))+
# xlim(-1.5,1.5) +
# ylim(0,4) +
geom_hline(yintercept = (-1)*log(cutoff.pvalue, 10), linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
geom_vline(xintercept = (-1)*cutoff.diff, linetype="dashed", colour="grey30", size=0.2) +
annotate("text", x=min(na.omit(drug.high.deg$diff.high2other), na.omit(drug.high.deg$diff.low2other)), y=max(na.omit((-1)*log(drug.high.deg$pvalue, 10)), na.omit((-1)*log(drug.low.deg$pvalue, 10)))*1.1, parse=FALSE, label = paste0("Signature.low cell lines: ", nrow(drug.share.signature.low)), color = "red", hjust = 0) +
geom_label_repel(aes(label=ifelse(drug.low.deg$pvalue < cutoff.pvalue & abs(drug.low.deg$diff.low2other) > cutoff.diff, as.character(drug.low.deg$TARGET_PATHWAY), "")), size = 2, color = ifelse(drug.low.deg$diff.low2other > 0, "blue", "red"), segment.size=0.2) +
labs(x="Sensitivity difference", y="-log10(p value)", title=paste0("Signature [", signature.name, "] Low vs. others"))
p4 <- p4 + theme_classic() + rremove("legend")
# p4
# Arranging the plot using cowplot
p = suppressWarnings(plot_grid(p1, p2, p3, p4, ncol = 2, align = "hv", rel_widths = c(1,1), rel_heights = c(1,1)))
# p <- ggplotGrob(p)
return(p)
}
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