## README: prepare Permutations, to make it more efficient
start.time  <-  Sys.time()


#########################
# LIBRARY AND FUNCTIONS #
#########################
library("checkmate")
assertClass(snakemake, "Snakemake")
assertDirectoryExists(snakemake@config$par_general$dir_scripts)
source(paste0(snakemake@config$par_general$dir_scripts, "/functions.R"))

initFunctionsScript(packagesReq = NULL, minRVersion = "3.1.0", warningsLevel = 1, disableScientificNotation = TRUE)
checkAndLoadPackages(c("tidyverse", "futile.logger", "checkmate", "tools", "methods"), verbose = FALSE)

# methods needed here because Rscript does not loads this package automatically, see http://stackoverflow.com/questions/19468506/rscript-could-not-find-function

########################################################################
# SAVE SNAKEMAKE S4 OBJECT THAT IS PASSED ALONG FOR DEBUGGING PURPOSES #
########################################################################
# snakemake=readRDS("/scratch/carnold/CLL/TF_act_noGCBias/output/Logs_and_Benchmarks/preparePermutations.R.rds")
createDebugFile(snakemake, "5.prepareBinning.R")

###################
#### PARAMETERS ###
###################

par.l = list()
par.l$verbose = TRUE
par.l$log_minlevel = "INFO"


#####################
# VERIFY PARAMETERS #
#####################

assertClass(snakemake, "Snakemake")

## INPUT ##
assertList(snakemake@input, min.len = 1)
assertSubset(names(snakemake@input), c("", "nucContent", "motifes"))

par.l$files_input_nucContentGenome  = snakemake@input$nucContent
for (fileCur in par.l$files_input_nucContentGenome) {
  assertFileExists(fileCur , access = "r")
}


par.l$file_input_TF_allMotives = snakemake@input$motifes
assertFileExists(par.l$file_input_TF_allMotives, access = "r")

## OUTPUT ##
assertList(snakemake@output, min.len = 1)
assertSubset(names(snakemake@output), c("", "allTFData", "allTFUniqueData"))

par.l$file_output_allTF       = snakemake@output$allTFData
par.l$file_output_allTFUnique = snakemake@output$allTFUniqueData


## CONFIG ##
assertList(snakemake@config, min.len = 1)

par.l$nPermutations = snakemake@config$par_general$nPermutations
assertIntegerish(par.l$nPermutations, lower = 0)


## PARAMS ##
assertList(snakemake@params, min.len = 1)
assertSubset(names(snakemake@params), c("", "nCGBins"))

par.l$nBins = as.integer(snakemake@params$nCGBins)
assertIntegerish(par.l$nBins, lower = 1, upper = 100)

## LOG ##
assertList(snakemake@log, min.len = 1)
par.l$file_log = snakemake@log[[1]]

allDirs = c(dirname(par.l$file_output_allTF), 
            dirname(par.l$file_output_allTFUnique),
            dirname(par.l$file_log)
)

testExistanceAndCreateDirectoriesRecursively(allDirs)


######################
# FINAL PREPARATIONS #
######################
startLogger(par.l$file_log, par.l$log_minlevel, removeOldLog = TRUE)
printParametersLog(par.l)


#########################
# READ ALL MOTIVES FILE #
#########################
# import original dataframe with motifs. Has to be read only once
TF.motifs.ori = read_tsv(par.l$file_input_TF_allMotives, col_names = TRUE, col_types = cols())

if (nrow(TF.motifs.ori) == 0) {
  message = paste0("The file ", par.l$file_input_TF_allMotives, " is empty. Something went wrong before. Make sure the previous steps succeeded.")
  flog.fatal(message)
  stop(message)
}

colnames(TF.motifs.ori) = c("permutation", "TF","chr","MSS","MES", "strand", "PSS","PES","annotation","ID","identifier","baseMean",
                            "l2FC","lfcSE","stat","pval","padj") # ,"VST_diff")

#Filter permutations in the original files that the user does not want anymore
TF.motifs.ori = filter(TF.motifs.ori, permutation <= par.l$nPermutations)

TF.motifs.ori$CG.identifier = paste0(TF.motifs.ori$TF,":",TF.motifs.ori$chr,":", TF.motifs.ori$MSS, "-", TF.motifs.ori$MES)

#########################
# READ ALL NUC CG FILES #
#########################

TF.motifs.CG = NULL

for (permutationCur in 0:par.l$nPermutations) {
  
  permutationName = paste0("permutation", permutationCur)
  
  if (permutationCur > 0) {
    flog.info(paste0("Reading file from permutation ", permutationCur))
  }
  
  fileCur = par.l$files_input_nucContentGenome[permutationCur+1]
  TF.motifs.CG.cur  = read_tsv(fileCur, col_names = TRUE, col_types = cols())
  
  colnames(TF.motifs.CG.cur) = c("chr","MSS","MES","strand","TF","AT","CG","A","C","G","T","N","other_nucl","length")
  
  nRowsNA = length(which(is.na(TF.motifs.CG.cur$CG)))
  if (nRowsNA > 0) {
    message <- paste0("The file ", fileCur, " contains ", nRowsNA, " rows out of ", nrow(TF.motifs.CG.cur), " with a missing value for the CG content, which most likely results from an assembly discordance between the BAM files and the specified fasta file. These regions will be removed in subsequent steps. The first 10 are printed with their first 3 columns here for debugging purposes:") 
    message = paste0(message, paste0(unlist(TF.motifs.CG.cur[1:10,"chr"]), ":", unlist(TF.motifs.CG.cur[1:10,"MSS"]), "-", unlist(TF.motifs.CG.cur[1:10,"MES"]), collapse = ", "))
    checkAndLogWarningsAndErrors(NULL, message, isWarning = TRUE)
    TF.motifs.CG.cur = TF.motifs.CG.cur[-nRowsNA,]
  }
  
  TF.motifs.CG.cur$permutation = permutationCur
  
  
  # Rbind and add permutation column
  if (is.null(TF.motifs.CG)){
    TF.motifs.CG = TF.motifs.CG.cur
  } else {
    TF.motifs.CG = rbind(TF.motifs.CG, TF.motifs.CG.cur)
  }
  
}


TF.motifs.CG$CG.identifier  = paste0(TF.motifs.CG$TF,":" ,TF.motifs.CG$chr ,":", TF.motifs.CG$MSS,  "-", TF.motifs.CG$MES)

#########
# MERGE #
#########
#TF.motifs.ori = filter(TF.motifs.ori, permutation<6)

# Remove duplicated rows
#TF.motifs.ori =  TF.motifs.ori[!duplicated(TF.motifs.ori),]


# concatenate the data in one df 

drop.cols = c( "A","C","G","T","N","other_nucl","length","chr.y","MSS.y","MES.y","strand.y","AT","CG.identifier","TF.y")

CGBins = seq(0,1, 1/par.l$nBins)

TF.motifs.all =  TF.motifs.ori %>% 
  full_join(TF.motifs.CG, by = c("CG.identifier", "permutation"))  %>% 
  select(-one_of(drop.cols)) %>% 
  mutate(CG.bins = cut(CG, breaks = CGBins, labels = paste0(round(CGBins[-1] * 100,0),"%"), include.lowest = TRUE)) %>%
  #rename(TF = TF.x, chr = chr.x, MSS = MSS.x, MES = MES.x, strand = strand.x)
  dplyr::rename(TF = TF.x, chr = chr.x, MSS = MSS.x, MES = MES.x)

# Not needed anymore, delete
rm(TF.motifs.CG)
rm(TF.motifs.ori)

# remove duplicated TFBS from different TFs to use in the permuations 
TF.motifs.all.unique = TF.motifs.all[!duplicated(TF.motifs.all[,c("permutation", "identifier")]),]

saveRDS(TF.motifs.all, file = par.l$file_output_allTF)
saveRDS(TF.motifs.all.unique, file = par.l$file_output_allTFUnique)