EGSEA: Ensemble of Gene Set Enrichment Analyses

# TODO: Add comment
# 
# Author: monther
###############################################################################


generateMainReport <- function(egseaResults, limma.tops = list(), 
        display.top = 20, sort.by = NULL, 
        report.dir = NULL, kegg.dir = NULL, 
        sum.plot.axis = NULL, sum.plot.cutoff = NULL, 
        num.threads = 4,
        print.base = FALSE,
        interactive = TRUE,
        verbose = FALSE){
    # print("HereReport1")
    # print(limma.tops)
    # create output directory for 'egsea' results
    message("EGSEA HTML report is being generated ...")
    start.time <- proc.time()
    timestamp()
    if (is.null(report.dir))
        report.dir = egseaResults@report.dir
    if (is.null(sort.by))
        sort.by = egseaResults@sort.by
    if (is.null(sum.plot.axis))
        sum.plot.axis = egseaResults@sum.plot.axis
    if (is.null(sum.plot.cutoff))
        sum.plot.cutoff = egseaResults@sum.plot.cutoff  
    contr.names = egseaResults@contr.names
    if (length(limma.tops) == 0 && 
            length(egseaResults@limmaResults) > 0){
        limma.tops = get.toptables(egseaResults@limmaResults,
                egseaResults@contrast)       
    }
    combineMethod = egseaResults@combineMethod
    baseGSEAs = egseaResults@baseMethods
    logFC = egseaResults@logFC
    logFC.calculated = egseaResults@logFC.calculated
    gs.annots = egseaResults@gs.annots
    symbolsMap = egseaResults@symbolsMap
    
    if (is.null(report.dir) || nchar(report.dir) == 0){
        timestamp = as.integer(as.numeric(Sys.time()))
        report.dir = paste0("./egsea_report_", timestamp)
    }
    if (! dir.exists(file.path(report.dir))){
        dir.create(file.path(report.dir), showWarnings = FALSE)        
    }else{
        warning("EGSEA report has been found. Change 'report.dir' to generate a fresh report.\n")
    }
    report.dir = normalizePath(report.dir)
    ranked.gs.dir = paste0(report.dir, "/ranked-gene-sets-base")
    dir.create(file.path(ranked.gs.dir), showWarnings = FALSE)
    summary.dir = paste0(report.dir, "/summary/")
    dir.create(file.path(summary.dir), showWarnings = FALSE)
    gs.annots = gs.annots[names(gs.annots) %in% names(egseaResults@results)]
    num.threads = optimizeNumThreads(num.threads, length(baseGSEAs), 
                                     length(contr.names), verbose)
    
    args.all = list()
    for (gs.annot in gs.annots){
      args.all[[gs.annot@label]] = list(gs.annot = gs.annot,
                                        egseaResults = egseaResults,
                                        sort.by = sort.by,
                                        display.top = display.top,
                                        verbose = verbose,
                                        print.base = print.base,
                                        baseGSEAs = baseGSEAs,
                                        contr.names = contr.names,
                                        sum.plot.cutoff=sum.plot.cutoff, 
                                        sum.plot.axis=sum.plot.axis,
                                        logFC = logFC,
                                        limma.tops = limma.tops,
                                        ranked.gs.dir = ranked.gs.dir,
                                        summary.dir = summary.dir,
                                        kegg.dir = kegg.dir,
                                        report.dir = report.dir,
                                        num.threads = num.threads,
                                        interactive=interactive
                                        )
    }    
    # print(args.all[[1]])
    results = lapply(args.all, generateMainReport.sub)
    # if (Sys.info()['sysname'] == "Windows" ||
    #     length(args.all) <= 1)
    #   results = lapply(args.all, generateMainReport.sub)
    # else{
    #   ## @importFrom BiocParallel bplapply MulticoreParam
    #   # multicoreParam <- MulticoreParam(workers = num.threads)
    #   # results = bplapply(args.all, generateMainReport.sub,
    #   #                    BPPARAM = multicoreParam)
    #   # noquote(tail(attr(results[[1]], "traceback")))
    #   results = mclapply(args.all, generateMainReport.sub, 
    #                      mc.cores = num.threads)
    # }
    
    createEGSEAReport(egseaResults@sampleSize, contr.names, 
            gs.annots, egseaResults@baseInfo, 
            combineMethod, sort.by,  report.dir,
            logFC.calculated, symbolsMap,
            egseaResults@egsea.version,
            egseaResults@egseaData.version)    
    if (interactive()) try(browseURL(paste0("file://", 
                                normalizePath(report.dir),
                                '/index.html')))
    elapsed.time = proc.time() - start.time    
    timestamp()
    message("EGSEA report generation took ", elapsed.time["elapsed"], " seconds.")
    message("EGSEA report has been generated.")
}

generateMainReport.sub <- function(args){
  # print("here1")
  gs.annot = args$gs.annot
  egseaResults = args$egseaResults
  sort.by = args$sort.by
  display.top = args$display.top
  verbose = args$verbose
  print.base = args$print.base
  baseGSEAs = args$baseGSEAs
  contr.names = args$contr.names
  sum.plot.cutoff = args$sum.plot.cutoff 
  sum.plot.axis = args$sum.plot.axis
  logFC = args$logFC
  limma.tops = args$limma.tops
  kegg.dir = args$kegg.dir
  ranked.gs.dir = args$ranked.gs.dir
  summary.dir = args$summary.dir
  report.dir = args$report.dir
  num.threads = args$num.threads
  symbolsMap = egseaResults@symbolsMap
  interactive = args$interactive
  # print("here2")
  message("Report pages and figures are being generated for the ",
          gs.annot@label, " collection ...")
  egsea.results = egseaResults@results[[gs.annot@label]]$test.results
  base.results = egseaResults@results[[gs.annot@label]]$base.results
  # order results based on the sort.by argument
  for (i in 1:length(egsea.results)){
    # sort based on the average ranking
    egsea.results[[i]] = egsea.results[[i]][
      order(egsea.results[[i]][, sort.by],
            decreasing=(sort.by == "significance")), 
      ]      
  }  
  # select top gene sets   
  gsets.top = egsea.selectTopGeneSets(egsea.results = egsea.results, 
                                      display.top = display.top, 
                                      gs.annot = gs.annot, 
                                      verbose= verbose) 
  # write out the base statistics if available 
  if (!is.null(base.results) && print.base){            
    write.base.stats(base.results, baseGSEAs, contr.names,
                     gs.annot, ranked.gs.dir, num.threads)
  }
  # generate summary heatmap for each collection 
  file.name.sum = paste0(summary.dir, gs.annot@label, 
                         "-summary-heatmap-", sort.by) 
  if (!file.exists(paste0(file.name.sum, ".png")))
    plotSummaryHeatmap(egseaResults, gs.annot$label, 
                       number = display.top,
                       sort.by = sort.by, hm.vals = "avg.logfc.dir",  
                       file.name = file.name.sum, 
                       format = NULL, verbose = verbose)
  # Generate heatmaps, pathways, GO graphs and summary plots
  if (length(grep("^kegg", gs.annot@label)) == 1){            
    plotPathways(gene.sets = gsets.top, fc=logFC, 
                 gs.annot=gs.annot, 
                 report.dir=report.dir, kegg.dir=kegg.dir, verbose = 
                   verbose)            
    file.name.pv = paste0(report.dir, "/pv-top-gs-", gs.annot@label, 
                          "/", 
                          contr.names,"-allPathways.html")
  }
  
  if ((length(grep("^c5", gs.annot@label)) == 1 || 
       length(grep("^gsdbgo", gs.annot@label)) == 1) && 
      "GOID" %in% colnames(gs.annot@anno)){
    plotGOGraphs(egsea.results=egsea.results,
                 gs.annot=gs.annot, report.dir=report.dir, sort.by=sort.by,
                 verbose)
    file.name.go = paste0(report.dir, "/go-graphs/", 
                          contr.names,"-", gs.annot@label,
                          "-allGOgraphs.html")
  }
  # print("HereReport2")
  # print(limma.tops)
  plotHeatMapsLogFC(gene.sets = gsets.top, fc=logFC, 
                    limma.tops = limma.tops,
                    gs.annot=gs.annot, 
                    symbolsMap=symbolsMap,
                    report.dir=report.dir)
  
  generateSumPlots(egsea.results = egsea.results, baseGSEAs = baseGSEAs, 
                   gs.annot = gs.annot, report.dir = report.dir,
                   sum.plot.cutoff = sum.plot.cutoff, 
                   sum.plot.axis = sum.plot.axis,
                   interactive = interactive)
  
  # Select the annotations of the top gene sets and generate HTLM 
  # reports 
  file.name = paste0(ranked.gs.dir, "/ranked-", gs.annot@label, 
                     "-gene-sets-", 
                     contr.names, '.txt')    
  file.name.hm = paste0(report.dir, "/hm-top-gs-", gs.annot@label, 
                        "/", 
                        contr.names,"-allHeatmaps.html")    
  file.name.sum = paste0(summary.dir,  sub(" - ", "-", 
                                           contr.names),
                         "-", gs.annot@label, "-summary.html")   
  
  # Create an HTML page for each contrast 
  for (i in 1:length(egsea.results)){  
    file.name.bar = paste0(summary.dir,                      
                           contr.names [i], "-", gs.annot@label, "-bar-plot-",
                           sort.by) 
    if (!file.exists(paste0(file.name.bar, ".png")))
      plotBars(egseaResults, gs.annot@label, contrast = i, 
               number = display.top, sort.by = sort.by,
               bar.vals = "p.adj",
               file.name = file.name.bar, 
               format = NULL, verbose=verbose)
    temp = egsea.results[[i]][1:ifelse(nrow(egsea.results[[i]]) > 
                                         display.top, 
                                       display.top, nrow(egsea.results[[i]])), ]
    if(interactive){
      writeEGSEAResultsToHTML(contr.names[i], egsea.results[[i]], gs.annot, 
                              file.name[i], interactive=interactive)
    }else{
      writeEGSEAResultsToHTML(contr.names[i], temp, gs.annot, 
                              file.name[i], interactive=interactive)
    }
    generateAllHeatmapsPage(contr.names[i], temp, gs.annot, 
                            file.name.hm[i])
    if (length(grep("^kegg", gs.annot@label)) == 1){
      generateAllPathwaysPage(contr.names[i], temp, 
                              gs.annot, file.name.pv[i])
    }
    if ((length(grep("^c5", gs.annot@label)) == 1 || 
         length(grep("^gsdbgo", gs.annot@label)) == 1) 
        && "GOID" %in% colnames(gs.annot@anno) ){
      generateAllGOgraphsPage(contr.names[i], gs.annot, sort.by,
                              file.name.go[i])
    }
    
    generateSummaryPage(contr.names[i], gs.annot, sum.plot.axis, 
                        sort.by, length(egsea.results), file.name.sum[i], interactive=interactive)
  }   
  # print out the comparison analysis pages
  if (length(gsets.top) > 1){      
    egsea.comparison.all = egseaResults@results[[gs.annot@label]]$comparison[["test.results"]]
    egsea.comparison.all = egsea.comparison.all[order(egsea.comparison.all[,sort.by]), ]
    egsea.comparison = egsea.comparison.all[1 : ifelse(
      nrow(egsea.comparison.all) > display.top, 
      display.top, nrow(egsea.comparison.all)), ]           
    # Comparison analysis reports generated here
    generateSumPlots.comparison(egsea.results = egsea.results, 
                                egsea.comparison = egsea.comparison.all, 
                                gs.annot = gs.annot, report.dir = report.dir, 
                                sum.plot.cutoff = sum.plot.cutoff, 
                                sum.plot.axis = sum.plot.axis,
                                interactive = interactive)    
    plotHeatMapsLogFC.comparison(gene.sets = 
                                   rownames(egsea.comparison), 
                                 fc=logFC,
                                 limma.tops = limma.tops,
                                 gs.annot=gs.annot, symbolsMap=symbolsMap,
                                 report.dir = report.dir)
    
    file.name.bar = paste0(summary.dir, "comparison-", gs.annot@label, 
                           "-bar-plot-", sort.by)
    file.name = paste0(ranked.gs.dir, "/ranked-", gs.annot@label, 
                       "-gene-sets-compare.txt")   
    file.name.hm = paste0(report.dir, "/hm-top-gs-", gs.annot@label, 
                          "/allHeatmaps.html")                
    file.name.sum = paste0(summary.dir,gs.annot@label, 
                           "-summary.html") 
    
    if (interactive)
      writeEGSEAResultsToHTML("Comparison Analysis", egsea.comparison.all,
                            gs.annot, file.name, comparison=TRUE, 
                            interactive = interactive)
    else
      writeEGSEAResultsToHTML("Comparison Analysis", egsea.comparison,
                              gs.annot, file.name, comparison=TRUE, 
                              interactive = interactive)
    if (!file.exists(paste0(file.name.bar, ".png")))
      plotBars(egseaResults, gs.annot@label, contrast = 0, 
               number = display.top, sort.by = sort.by,
               bar.vals = "p.adj",
               file.name = file.name.bar, 
               format = NULL, verbose=verbose)
    
    generateAllHeatmapsPage("Comparison Analysis", egsea.comparison
                            , gs.annot, file.name.hm, comparison=TRUE)
    
    if (length(grep("^kegg", gs.annot@label)) == 1){
      plotPathways.comparison(gene.sets = 
                                rownames(egsea.comparison), fc=logFC, 
                              gs.annot=gs.annot, 
                              report.dir=report.dir, kegg.dir=kegg.dir, verbose = 
                                verbose)    
      file.name.pv = paste0(report.dir, "/pv-top-gs-", 
                            gs.annot@label,"/allPathways.html") 
      generateAllPathwaysPage("Comparison Analysis", 
                              egsea.comparison, 
                              gs.annot, file.name.pv, comparison=TRUE)
    }   
    if ((length(grep("^c5", gs.annot@label)) == 1 || 
         length(grep("^gsdbgo", gs.annot@label)) == 1)  && 
        "GOID" %in% colnames(gs.annot@anno)){
      plotGOGraphs.comparison(egsea.results=egsea.comparison.all,
                              gs.annot=gs.annot, report.dir=report.dir, sort.by=sort.by)
      file.name.go = paste0(report.dir, 
                            "/go-graphs/", gs.annot@label ,"-allGOgraphs.html")  
      generateAllGOgraphsPage.comparison(contr.names, 
                                         gs.annot, sort.by, file.name.go) 
    }
    
    generateSummaryPage.comparison(contr.names, gs.annot, sum.plot.axis,
                                   sort.by, file.name.sum, interactive=interactive)  
  } 
}

write.base.stats <- function(base.results, baseGSEAs, contr.names,
        gs.annot, ranked.gs.dir, num.threads){
    args.all = list()
    i = 1
    for (method in baseGSEAs){
        for (contrast in contr.names){                   
            base.results.ind = base.results[[contrast]][[method]]
            file.name = paste0(ranked.gs.dir, "/", method,
                    "-ranked-", 
                    gs.annot@label, "-gene-sets-", 
                    contrast, '.txt')                    
            args.all[[i]] = list(
                    base.frame = base.results.ind[order(
                                    base.results.ind[,"Rank"]), ],
                    contrast = contrast,
                    gs.annot = gs.annot,
                    method = toupper(method),
                    file.name = file.name)
            i = i + 1
        }
    }
    if (Sys.info()['sysname'] == "Windows" ||
            length(args.all) <= 1)
        results = lapply(args.all, write.base.results)
    else
        results = mclapply(args.all, write.base.results, 
                mc.cores = num.threads)
    
}

write.base.results <- function(args){
    writeResultsToHTML(args$contrast, args$base.frame, 
            args$gs.annot, args$method, args$file.name)
}