#!/usr/bin/env Rscript
# example:
# Rscript RNAseq_sexcheck.R -i geneexp_log2fpkm.txt 
# Rscript RNAseq_sexcheck.R -i FUSCCTNBC_RNAseqShi.Complete_log2_448x45308_V15_190209.txt -p 111 -s ./sexgenelist.txt -e GeneSymbol
 
suppressPackageStartupMessages(library("optparse"))

# specify our desired options in a list
# by default OptionParser will add an help option equivalent to 
# make_option(c("-h", "--help"), action="store_true", default=FALSE, 
#               help="Show this help message and exit")

option_list <- list( 
    make_option(c("-o", "--out_dir"), type="character",default="./",
        help="The output directory [default ./]"),
    make_option(c("-i", "--input"),type="character", default=NULL,
        help="The input expression files. required!"),
	make_option(c("-e", "--type_gene_id"),type="character", default="EnsemblID",
        help="The type of gene symbol. Could be either of EnsemblID/EntrezID/GeneSymbol [default: EnsemblID]"),
	make_option(c("-b", "--pre_lowexpr_filtered"), metavar="FALSE",default=FALSE,
        help="Where pre-filterd low expressed genes. [default: FALSE]"),
    make_option(c("-s", "--sex_genes"),type="character",  default="./sexgenelist.txt",
        help="File in tab-delimited format sex gene list with EnsemblID/EntrezID/GeneSymbol. [default: ./sexgenelist.txt ]"),
   make_option(c("-p", "--project_code"), type="character",default="rnaseq",
        help="Project code, which is used as prefix of output file. [default: rnaseq]")
		)
		
# get command line options, if help option encountered print help and exit,
# otherwise if options not found on command line then set defaults, 
opt <- parse_args(OptionParser(option_list=option_list))

#pre analysis
if (is.null(opt$input)){
  print_help(opt_parser)
  stop("At least one argument must be supplied (input file).", call.=FALSE)
}

##import exp file
out_dir<-paste(gsub("/$","",opt$out_dir),"/",sep="")

logexpr<-read.table(opt$input,header=T,stringsAsFactors=F,row.names=1,check.names=F)

#check exp file is log scale
if(max(logexpr[,1])-min(logexpr[,1])>100){
  stop("sex check anlaysis should be conducted based on expression profile on log scale.", call.=FALSE)
}

####import sex gene list
sexgene<-read.delim(opt$sex_genes,header=T,stringsAsFactors=F,check.names=F)

#
if(grepl("Ensembl",opt$type_gene_id,ignore.case=T)){
sexgenelist<-as.character(sexgene$EnsemblID)
}
if(grepl("Entrez",opt$type_gene_id,ignore.case=T)){
sexgenelist<-as.character(sexgene$EntrezID)
}
if(grepl("Symbol",opt$type_gene_id,ignore.case=T)){
sexgenelist<-as.character(sexgene$GeneSymbol)
}

sexexpr<-logexpr[rownames(logexpr) %in% sexgenelist, ]

if(nrow(sexexpr)<=(length(sexgenelist)/2)){
  stop("Not sufficent expression profile sex specific genes were detected for sex prediction. Please check rowname is matched with type_gene_id in the command.", call.=FALSE)
}

#get median value without 
#if pre_lowexpr_filtered = FALSE, remove not expressed values before obtaining median value 

if (opt$pre_lowexpr_filtered){
medians<-apply(logexpr,2,median)
}else{
minvalue<- min(as.numeric(logexpr)[!is.na(as.numeric(logexpr))])
medians<-apply(logexpr,2,function(x){median(x[which(x> minvalue)])})
}

#sexexpr1<-sexexpr[apply(sexexpr,1,function(x){length(which(x<( -6)))}<13),]

#if all of the genes expressed lower than median: female, else male
sexpredict<-ifelse(rowSums(apply(sexexpr,1,function(x){ifelse(x-medians>0,1,0)}))>2,"Male","Female")
sexpredict_tab<-data.frame(
Sample=names(sexpredict),
Sex=sexpredict
)
rownames(sexpredict_tab)<-c(1:nrow(sexpredict_tab))

write.csv(sexpredict_tab,paste(out_dir,opt$project_code,"_sexpredict.csv",sep=""),quote=F,row.names=F)
saveRDS(sexpredict_tab,paste(out_dir,opt$project_code,"_sexpredict.rds",sep=""))
message("RNAseq_sexcheck.R finished!")