#' survAnal: runs cox proportional hazard models against patients with top and bottom n percent expression values
#'
#' The runCPH function will process three separate file one with sample ids one with survival data and one with
#' expression values. In test mode if a list of sample ids are supplied but not the other two files it assumes the
#' ids are from the TCGA SKCM data set and uses a cached version of the normalised expression values from the TCGA
#' SKCM data set and a currated set of survival data.
#'
#' It will also perform a limma differential gene expression test for the significance of the fold change between the
#' top and bottom n percent of expression values
#'
#' @param geneData names of the genes to be tested (must be in the rownames of exprData)
#' @param survData survival data must contain a time and status
#' @param exprData normalised gene expression data
#' @param percExpr filter for minimum percentage of samples required to be expression a gene
#' to select genes for testing
#' @param exprRange top and bottom quantiles of expression values to select samples for testing
#' @param sep default separator for delimited survival and sample id files supplied
#' @param exprSep default separator for expression file supplied
#' @param outputDir location to write output files
#' @param analysisName stub to add to output file names
#' @param silent boolean return the full set of statistics as a data frame
#'
#' @return the function creates several csv output files with the Cox PH results, the Limma DGE results, a combined set
#' of both results and a set of those genes for which the DGE result is significant at 0.05 FDR
#'
#' @examples
#' analysisName="test3"
#' exprSep=","
#' res <- runCPH(sampleDataFile=sampleDataFile,expressionDataFile=expressionDataFile,
#' survivalDataFile=survivalDataFile,
#' analysisName=analysisName,exprSep=exprSep)
#'
#' @export
survClust <- function(survData=NULL, exprData=NULL,geneData=NULL,survTime="time", cox=F,plotIt=F,
survStatus="status",mcores=4, clustCol="sampleCl",verbose=FALSE){
require(survival)
# Filter by samples in sample data just incase
exprSamples <- colnames(exprData)
survSamples <- rownames(survData)
# Sanity check the sample ids are the same
if(!identical(unique(sort(exprSamples)), sort(survSamples))){
stop(paste0("The samples in ",paste0(survSamples,collapse=",")," do not match those in the ",
"expression and survival data files"))
}
if(!identical(sort(exprSamples), sort(survSamples))){
warning(paste0("The samples in ",survSamples," potentially have more than one expression",
" sample"))
}
mcParam <- BiocParallel::MulticoreParam(workers=mcores)
exprData[which(!is.finite(exprData))] <- min(exprData[which(is.finite(exprData))])
exprData2 <- t(exprData[which(rownames(exprData)%in%geneData),])
survData2 <- merge(survData[,c(survTime,survStatus,clustCol)], exprData2,by="row.names")
rownames(survData2) <- survData2[,1]
survData2[,clustCol] <- as.factor(survData2[,clustCol])
# filter out genes not expressed in percentage of samples
# run cox proportional hazard on all expressed genes
# get max of either days to death or days to last follow up for time
# Censor the time data to generate survival data
form <- paste0("Surv( ",survTime,",",survStatus,") ~ ",clustCol," -1")
# fit cox proportional hazards (non-parametric) survival model
if(cox){
fit <- survival::coxph(as.formula(form),data=survData2)
}else{
fit <- survival::survfit(as.formula(form),data=survData2)
}
return(list(fit=fit,kmplot=plotKM(as.formula(form),dat=survData2)))
}
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