R/main.R

Defines functions .excludeSamplesFromList .backwardsCompatibility .createR2CExport .userRefdb .userOrg .reduceGeneData constructGeneModel metaseqr2

Documented in metaseqr2

metaseqr2 <- function(
    counts,
    sampleList,
    excludeList=NULL,
    fileType=c("auto","sam","bam","bed"),
    path=NULL,
    contrast=NULL,
    libsizeList=NULL,
    embedCols=list(
        idCol=4,
        gcCol=NA,
        nameCol=NA,
        btCol=NA
    ),
    annotation=NULL,
    org=c("hg18","hg19","hg38","mm9","mm10","rn5","rn6","dm3","dm6",
        "danrer7","pantro4","susscr3","tair10","equcab2"),
    refdb=c("ensembl","ucsc","refseq"),
    version="auto",
    transLevel=c("gene","transcript","exon"),
    countType=c("gene","exon","utr"),
    utrOpts=list(
        frac=1,
        minLength=300,
        downstream=50
    ),
    exonFilters=list(
        minActiveExons=list(
            exonsPerGene=5,
            minExons=2,
            frac=1/5
        )
    ),
    geneFilters=list(
        length=list(
            length=500
        ),
        avgReads=list(
            averagePerBp=100,
            quantile=0.25
        ),
        expression=list(
            median=TRUE,
            mean=FALSE,
            quantile=NA,
            known=NA,
            custom=NA
        ),
        biotype=getDefaults("biotypeFilter",org[1]),
        presence=list(
            frac=0.25,
            minCount=10,
            perCondition=FALSE
        )
    ),
    whenApplyFilter=c("postnorm","prenorm"),
    normalization=c("deseq","deseq2","edaseq","edger","noiseq","nbpseq",
        "absseq","dss","each","none"),
    normArgs=NULL,
    statistics=c("deseq","deseq2","edger","noiseq","bayseq","limma","nbpseq",
        "absseq","dss"),
    statArgs=NULL,
    adjustMethod=sort(c(p.adjust.methods,"qvalue")),
    metaP=if (length(statistics)>1) c("simes","bonferroni","fisher",
        "dperm_min","dperm_max","dperm_weight","fperm","whitlock","minp","maxp",
        "weight","pandora","none") else "none",
    weight=rep(1/length(statistics),length(statistics)),
    nperm=10000,
    pcut=NA,
    logOffset=1,
    pOffset=NULL,
    preset=NULL, # An analysis strictness preset
    qcPlots=c(
        "mds","biodetection","countsbio","saturation","readnoise","filtered",
        "correl","pairwise","boxplot","gcbias","lengthbias","meandiff",
        "meanvar","rnacomp","deheatmap","volcano","biodist","mastat","statvenn",
        "foldvenn","deregulogram"
    ),
    figFormat=c("png","jpg","tiff","bmp","pdf","ps"),
    outList=FALSE,
    exportWhere=NA, # An output directory for the project
    exportWhat=c("annotation","p_value","adj_p_value","meta_p_value",
        "adj_meta_p_value","fold_change","stats","counts","flags"),
    exportScale=c("natural","log2","log10","vst","rpgm"),
    exportValues=c("raw","normalized"),
    exportStats=c("mean","median","sd","mad","cv","rcv"),
    exportCountsTable=FALSE,
    restrictCores=0.6,
    report=TRUE,
    reportTop=0.1,
    reportTemplate="default",
    saveGeneModel=TRUE,
    verbose=TRUE,
    runLog=TRUE,
    reportDb=c("dexie","sqlite"),
    localDb=file.path(system.file(package="metaseqR2"),"annotation.sqlite"),
    offlineReport=TRUE,
    createTracks=FALSE,
    overwriteTracks=FALSE,
    trackExportPath=file.path(exportWhere,"tracks"),
    trackInfo=list(
        stranded=FALSE,
        normTo=1e+9,
        urlBase="http://www.trackserver.me",
        fasta=NULL,
        gtf=NULL,
        hubInfo=list(
            name="MyHub",
            shortLabel="My hub",
            longLabel="My hub long",
            email="someone@example.com"
        )
    ),
    .progressFun=NULL,
    .exportR2C=FALSE,
    ...
) {
    # Save function call for report
    FUN_CALL <- deparse(sys.call())
    
    # Check for older argument names and adjust
    args <- as.list(match.call())
    backCheckedArgs <- .backwardsConvertArgs(args)
    if (backCheckedArgs$mixDetected)
        stop("You must provide either old metaseqR arguments (e.g sample.list)",
            " or new metaseqR2 arguments (e.g. sampleList)! Not both!")
    if (backCheckedArgs$backDetected) {
        argMap <- .backwardsMapOld2New()
        # Check what happens with the new argument embedCols
        if (!is.null(backCheckedArgs$args$embedCols)) {
            embedCols <- backCheckedArgs$args$embedCols
            backCheckedArgs$args$embedCols <- NULL
        }
        for (n in names(backCheckedArgs$args))
            assign(argMap[[n]],eval(backCheckedArgs$args[[n]]))
        # There are some nested arguments that also need correction
        if (!is.null(backCheckedArgs$args$gene.filters)) {
            if (!is.null(geneFilters$avg.reads)) {
                geneFilters$avgReads <- geneFilters$avg.reads
                if (!is.null(geneFilters$avg.reads$average.per.bp)) {
                    geneFilters$avgReads$averagePerBp <-
                        geneFilters$avg.reads$average.per.bp
                    geneFilters$avg.reads$average.per.bp <- NULL
                }
                geneFilters$avg.reads <- NULL
            }
            if (!is.null(geneFilters$presence)) {
                if (!is.null(geneFilters$presence$min.count)) {
                    geneFilters$presence$minCount <-
                        geneFilters$presence$min.count
                    geneFilters$presence$min.count <- NULL
                }
                if (!is.null(geneFilters$presence$per.condition)) {
                    geneFilters$presence$perCondition <-
                        geneFilters$presence$per.condition
                    geneFilters$presence$per.condition <- NULL
                }
            }
        }
        if (!is.null(backCheckedArgs$args$exon.filters)) {
            if (!is.null(exonFilters$min.active.exons)) {
                exonFilters$minActiveExons <- exonFilters$min.active.exons
                if (!is.null(exonFilters$min.active.exons$exons.per.gene)) {
                    exonFilters$minActiveExons$exonsPerGene <-
                        exonFilters$min.active.exons$exons.per.gene
                    exonFilters$min.active.exons$exons.per.gene <- NULL
                }
                if (!is.null(exonFilters$min.active.exons$min.exons)) {
                    exonFilters$minActiveExons$minExons <-
                        exonFilters$min.active.exons$min.exons
                    exonFilters$min.active.exons$min.exons <- NULL
                }
                exonFilters$min.active.exons <- NULL
            }
        }
        if ("venn" %in% qcPlots)
            qcPlots[which(qcPlots == "venn")] <- "statvenn"
        if (annotation == "download")
            annotation <- NULL
    }
    else
        # Check if there are any mispelled or invalid parameters and throw a
        # warning
        checkMainArgs(args)    
    
    # Check essential arguments
    fromRaw <- fromPrevious <- FALSE
    if (missing(counts) && (missing(sampleList) || is.list(sampleList)))
        stop("You must provide a file with genomic region (gene, exon, etc.) ",
            "counts\nor an input targets file to create input from! If the ",
            "counts file is\nmissing, sampleList cannot be missing or it must ",
            "be a targets file\nwith at least three columns! See the ",
            "readTargets function.\ncounts may also be a gene model list ",
            "(see the documentation)")
    if (!missing(counts) && !missing(sampleList) && is.character(counts) 
        && file.exists(counts) && length(grep(".RData$",counts))>0) {
        warning("When restoring a previous analysis, sampleList argument is ",
            "not necessary! Ignoring...",immediate.=TRUE)
        fromPrevious <- TRUE
        disp("Restoring previous analysis from ",basename(counts))
        tmpEnv <- .backwardsCompatibility(counts)
        sampleList <- tmpEnv$sampleList
        countType <- tmpEnv$countType
    }
    if (!missing(counts) && missing(sampleList) && is.character(counts) 
        && file.exists(counts) && length(grep(".RData$",counts))>0) {
        # Time to load previous analysis if existing
        fromPrevious <- TRUE
        message("Restoring previous analysis from ",basename(counts))
        tmpEnv <- .backwardsCompatibility(counts)
        sampleList <- tmpEnv$sampleList
        countType <- tmpEnv$countType
    }
    if (missing(sampleList) && !fromPrevious || (!is.list(sampleList) &&
        !file.exists(sampleList)))
        stop("You must provide a list with condition names and sample names ",
            "(same as in the counts file) or an input file to create the ",
            "sample list from!")
    if (!missing(sampleList) && !is.list(sampleList) 
        && file.exists(sampleList) && !missing(counts) && !fromPrevious)
        sampleList <- makeSampleList(sampleList)
    if (!missing(sampleList) && !is.list(sampleList) 
        && file.exists(sampleList) && missing(counts)) {
        counts <- NULL
        theList <- readTargets(sampleList,path=path)
        sampleList <- theList$samples
        fileList <- theList$files
        if (tolower(fileType[1])=="auto")
            fileType <- theList$type
        if (is.null(fileType))
            stop(paste("The type of the input files could not be recognized!",
                "Please specify (BAM or BED)..."))
        fromRaw <- TRUE
    }
    else
        theList <- NULL
    
    # If report requested with SQLite RSQLite must be present,also pander
    if (report) {
        if (!requireNamespace("pander"))
            stop("R package pander is required to build metaseqR2 reports!")
        if ("sqlite" %in% reportDb && !requireNamespace("RSQLite"))
            stop("R package RSQLite is required to build metaseqR reports!")
    }
    
    # Initialize environmental variables
    HOME <- system.file(package="metaseqR2")
    TEMPLATE <- HOME
    # Globalize the project's verbosity and logger
    if (fromRaw)
        PROJECT_PATH <- makeProjectPath(exportWhere)
    else
        PROJECT_PATH <- makeProjectPath(exportWhere,counts)
    assign("VERBOSE",verbose,envir=metaEnv)
    if (runLog) {
        if (file.exists(file.path(PROJECT_PATH$logs,"metaseqr_run.log")))
            unlink(file.path(PROJECT_PATH$logs,"metaseqr_run.log"))
        logger <- create.logger(logfile=file.path(PROJECT_PATH$logs,
            "metaseqr_run.log"),level=2,logformat="%d %c %m")
    }
    else
        logger <- NULL
    assign("LOGGER",logger,envir=metaEnv)
    
    # Check if sample names match in file/df and list, otherwise meaningless to 
    # proceed
    if (!fromRaw && !fromPrevious) {
        if (!is.data.frame(counts) && !is.list(counts)) {
            if (file.exists(counts)) {
                aline <- read.delim(counts,nrows=5) # Read the 1st lines
                aline <- colnames(aline)
            }
            else
                stopwrap("The counts file you provided does not exist!")
        }
        else if (is.data.frame(counts))
            aline <- colnames(counts)
        else if (is.list(counts))
            aline <- names(counts)
        samples <- unlist(sampleList,use.names=FALSE)
        if (length(which(!is.na(match(samples,aline)))) != length(samples))
            stopwrap("The sample names provided in the counts file/list do ",
                "not match with those of the sampleList!")
    }
    
    # If exclude list given, check that it's a subset of sampleList, otherwise
    # just ignore excludeList
    if (!is.null(excludeList) && !is.na(excludeList)) {
        sl <- unlist(sampleList)
        el <- unlist(excludeList)
        if (length(intersect(sl,el)) != length(el)) {
            warnwrap("Some samples in excludeList do not match those in the ",
                "initial sampleList! Ignoring...",now=TRUE)
            excludeList <- NULL
        }
    }

    fileType <- tolower(fileType[1])
    org <- tolower(org[1])
    refdb <- tolower(refdb[1])
    version <- version[1]
    transLevel <- tolower(transLevel[1])
    countType <- tolower(countType[1])
    whenApplyFilter <- tolower(whenApplyFilter[1])
    normalization <- tolower(normalization[1])
    adjustMethod <- adjustMethod[1]
    metaP <- tolower(metaP[1])
    statistics <- tolower(statistics)
    figFormat <- tolower(figFormat)
    if (!is.null(qcPlots)) 
        qcPlots <- tolower(qcPlots)
    exportWhat <- tolower(exportWhat)
    exportScale <- tolower(exportScale)
    exportValues <- tolower(exportValues)
    exportStats <- tolower(exportStats)
    reportDb <- tolower(reportDb[1])
    if (!is.null(preset)) 
        preset <- tolower(preset[1])
    
    if (fromRaw)
        countsName <- "imported sam/bam/bed files"
    else {
        if (!is.data.frame(counts) && !is.null(counts) && !is.list(counts)) {
            checkFileArgs("counts",counts)
            if (fromPrevious)
                countsName <- "previously stored project"
            else
                countsName <- basename(counts)
        }
        else if (is.list(counts) && !is.data.frame(counts)) {
            countsName <- "previously stored gene model"
        }
        else {
            countsName <- "imported custom data frame"
        }
    }
    
    # annotation cannot be "embedded" when countType is other than "gene" or
    # transLevel is other than "gene"
    if (!is.null(annotation) && !is.list(annotation)
        && is.character(annotation) && annotation == "embedded" 
        && countType != "gene")
        stopwrap("The annotation argument cannot be \"embedded\" when the ",
            "countType argument is other than \"gene\"!")

    # annotation must be a list to be fed to buildCustomAnnotation
    if (is.list(annotation)) {
        # members are checked by buildCustomAnnotation if required
        # We only need to check that the gtfFile exists here
        if (!("gtf" %in% names(annotation)))
            stopwrap("A gtf field must be provided with an existing GTF file ",
                "when providing a list with custom annotation elements!")
        if ("gtf" %in% names(annotation) && is.character(annotation$gtf)
            && !file.exists(annotation$gtf))
            stopwrap("An existing GTF file must be provided when providing a ",
                "list with custom annotation elements!")
    }
    
    if (is.list(counts) && !is.data.frame(counts)
        && (countType=="exon" || countType=="utr")
        && annotation=="embedded") {
        warnwrap("annotation cannot be \"embedded\" when importing a stored ",
            "gene model! Setting to NULL...")
        #annotation <- "download"
        annotation <- NULL
    }

    if (metaP %in% c("weight","pandora","dperm_weight") && 
        abs(1-sum(weight))>1e-5)
        stopwrap("The weights given for p-value combination should sum to 1!")

    checkTextArgs("fileType",fileType,c("auto","sam","bam","bed"),
        multiarg=FALSE)
    if (!is.null(annotation) && !is.list(annotation) 
        && !file.exists(annotation))
        checkTextArgs("annotation",annotation,"embedded",multiarg=FALSE)
    if (is.character(localDb) && file.exists(localDb)) {
        if (!.userOrg(org,localDb) && is.null(annotation))
            checkTextArgs("org",org,c("hg18","hg19","hg38","mm9","mm10","rn5",
                "rn6","dm3","dm6","danrer7","pantro4","susscr3","tair10",
                "equcab2"),multiarg=FALSE)
    }
    else if (is.null(annotation) 
        && !(is.character(localDb) || file.exists(localDb))) {
        # So only some annotations can be fetched on-the-fly
        checkTextArgs("org",org,c("hg18","hg19","hg38","mm9","mm10","rn5","rn6",
            "dm3","dm6","danrer7","pantro4","susscr3","tair10","equcab2"),
            multiarg=FALSE)
    }
    if (is.character(localDb) && file.exists(localDb)) {
        if (!.userRefdb(refdb,localDb) && is.null(annotation))
            checkTextArgs("refdb",refdb,c("ensembl","ucsc","refseq"),
                multiarg=FALSE)
    }
    else if (is.null(annotation) 
        && !(is.character(localDb) || file.exists(localDb))) {
        checkTextArgs("refdb",refdb,c("ensembl","ucsc","refseq"),multiarg=FALSE)
    }
    checkTextArgs("transLevel",transLevel,c("gene","transcript","exon"),
        multiarg=FALSE)
    checkTextArgs("countType",countType,c("gene","exon","utr"),
        multiarg=FALSE)
    checkTextArgs("whenApplyFilter",whenApplyFilter,c("postnorm",
        "prenorm"),multiarg=FALSE)
    checkTextArgs("normalization",normalization,c("edaseq","deseq","deseq2",
        "edger","noiseq","nbpseq","absseq","dss","each","none"),multiarg=FALSE)
    if (!any(is.na(statistics)))
        checkTextArgs("statistics",statistics,c("deseq","deseq2","edger",
            "noiseq","bayseq","limma","nbpseq","absseq","dss"),multiarg=TRUE)
    checkTextArgs("metaP",metaP,c("simes","bonferroni","fisher","dperm_min",
        "dperm_max","dperm_weight","fperm","whitlock","minp","maxp","weight",
        "pandora","none"),multiarg=FALSE)
    checkTextArgs("figFormat",figFormat,c("png","jpg","tiff","bmp","pdf",
        "ps"),multiarg=TRUE)
    checkTextArgs("exportWhat",exportWhat,c("annotation","p_value",
        "adj_p_value","meta_p_value","adj_meta_p_value","fold_change","stats",
        "counts","flags"),multiarg=TRUE)
    checkTextArgs("exportScale",exportScale,c("natural","log2","log10",
        "rpgm","vst"),multiarg=TRUE)
    checkTextArgs("exportValues",exportValues,c("raw","normalized"),
        multiarg=TRUE)
    checkTextArgs("exportStats",exportStats,c("mean","median","sd","mad",
        "cv","rcv"),multiarg=TRUE)
    checkTextArgs("reportDb",reportDb,c("sqlite","dexie"))
    if (!is.null(preset))
        checkTextArgs("preset",preset,c("all_basic","all_normal","all_full",
            "medium_basic","medium_normal","medium_full","strict_basic",
            "strict_normal","strict_full"),multiarg=FALSE)
    if (!is.null(qcPlots))
        checkTextArgs("qcPlots",qcPlots,c("mds","biodetection","countsbio",
            "saturation","readnoise","correl","pairwise","boxplot","gcbias",
            "lengthbias","meandiff","meanvar","rnacomp","deheatmap","volcano",
            "biodist","filtered","mastat","statvenn","foldvenn","deregulogram"),
            multiarg=TRUE)
    if (!is.na(restrictCores)) checkNumArgs("restrictCores",restrictCores,
        "numeric",c(0,1),"botheq")
    if (!is.na(pcut)) 
        checkNumArgs("pcut",pcut,"numeric",c(0,1),"botheq")
    if (!is.null(embedCols$gcCol) && !is.na(embedCols$gcCol)) 
        checkNumArgs("embedCols$gcCol",embedCols$gcCol,"numeric",0,"gt")
    if (!is.null(embedCols$nameCol) && !is.na(embedCols$nameCol)) 
        checkNumArgs("embedCols$nameCol",embedCols$nameCol,"numeric",0,"gt")
    if (!is.null(embedCols$btCol) && !is.na(embedCols$btCol)) 
        checkNumArgs("embedCols$btCol",embedCols$btCol,"numeric",0,"gt")
    if (!is.na(logOffset)) 
        checkNumArgs("logOffset",logOffset,"numeric",0,"gt")
    if (!is.null(pOffset)) 
        checkNumArgs("pOffset",pOffset,"numeric",c(0,1),"botheq")
    checkNumArgs("nperm",nperm,"numeric",10,"gt")
    if (!is.null(reportTop))
        checkNumArgs("reportTop",reportTop,"numeric",c(0,1),"both")
    if (!is.null(contrast)) {
        checkContrastFormat(contrast,sampleList)
        contrast <- unique(contrast)
    }
    if ("bayseq" %in% statistics) 
        libsizeList <- checkLibsize(libsizeList,sampleList)
    # Check the genomic database version argument
    if (is.character(version)) {
        version <- tolower(version)
        checkTextArgs("version",version,c("auto"),multiarg=FALSE)
    }
    else
        checkNumArgs("version",version,"numeric")
    
    # Check utrOpts if countType is "utr"
    if (countType == "utr") {
        utrOptsDef <- getDefaults("utrOpts")
        if (!is.null(utrOpts$frac)) {
            checkNumArgs("utrOpts$frac",utrOpts$frac,"numeric",c(0,1),"both")
            utrOptsDef$frac <- utrOpts$frac
        }
        if (!is.null(utrOpts$minLength)) {
            checkNumArgs("utrOpts$minLength",utrOpts$minLength,"numeric",0,
                "gt")
            utrOptsDef$minLength <- utrOpts$minLength
        }
        if (!is.null(utrOpts$downstream)) {
            checkNumArgs("utrOpts$downstream",utrOpts$downstream,"numeric",0,
                "gte")
            utrOptsDef$downstream <- utrOpts$downstream
        }
        utrOpts <- utrOptsDef
    }
    
    # Check main functionality packages
    checkPackages(metaP,qcPlots)
    # Check the case of embedded annotation, not given gc and gene name columns
    # Checks about countType have been performed before
    if (!is.null(annotation) && annotation == "embedded") {
        if (is.na(embedCols$gcCol) && countType=="gene" 
            && normalization=="edaseq")
            stopwrap("The column that contains the gene GC content ",
                "(\"embedCols$gcCol\") argument is required when ",
                "\"annotation\" is \"embedded\"!")
                
        if (is.na(embedCols$nameCol) && !is.na(geneFilters$expression$known)) {
            warnwrap("The column that contains the HUGO gene symbols ",
                "(\"embedCols$nameCol\") is missing with embedded annotation! ",
                "Gene name expression filter will not be available...")
            geneFilters$expression$known=NA
            if ("volcano" %in% qcPlots)
                warnwrap("The column that contains the HUGO gene symbols ",
                    "(\"embedCols$nameCol\") is missing with embedded ",
                    "annotation! Interactive volcano plots will not contain ",
                    "gene names...")
        }
        
        if (is.na(embedCols$btCol) && countType=="gene") {
            warnwrap("The column that contains the gene biotypes ",
                "(\"embedCols$btCol\") is missing with embedded annotation! ",
                "Biotype filters and certain plots will not be available...")
            geneFilters$biotype=NULL
            toRemove <- match(c("biodetection","countsbio","saturation",
                "biodist","filtered","rnacomp","readnoise"),qcPlots)
            noMatch <- which(is.na(toRemove))
            if (length(noMatch)>0)
                toRemove <- toRemove[-noMatch]
            if (length(toRemove)>0)
                qcPlots <- qcPlots[-toRemove]
        }
    }
    if (org %in% c("hg18","hg38","mm10") && (refdb %in% c("ucsc","refseq"))) {
        warnwrap("Gene/exon biotypes cannot be retrieved when organism is ",
            "\"hg18\", \"hg38\", \"mm10\" and annotation database is ",
            "\"ucsc\" or \"refseq\"!\nBiotype filters and certain plots will ",
            "not be available...")
        geneFilters$biotype=NULL
        toRemove <- match(c("biodetection","countsbio","saturation",
            "biodist","filtered"),qcPlots)
        noMatch <- which(is.na(toRemove))
        if (length(noMatch)>0)
            toRemove <- toRemove[-noMatch]
        if (length(toRemove)>0)
            qcPlots <- qcPlots[-toRemove]
    }
    if (transLevel %in% c("transcript","exon")) {
        warnwrap("When transLevel is \"transcript\" or \"exon\", the GC bias ",
            "plots are not available.")
        if ("gcbias" %in% qcPlots)
            qcPlots <- qcPlots[-which(qcPlots == "gcbias")]
    }
    
    # In case someone wants a simple exon analysis but has not understood well
    # the docs of transLevel and countType...
    if (transLevel == "exon" && countType == "exon") {
        warnwrap("You have chosen transLevel=\"exon\" and countType=\"exon\".",
            "\nYou are probably trying to perform simple differential exon ",
            "analysis. This can be perofmed\nby setting transLevel=\"exon\" ",
            "and countType=\"gene\". Setting for you...")
        countType <- "gene"
    }
    
    # Remove biodist and volcano if no statistics or contrast
    if ("biodist" %in% qcPlots && (any(is.na(statistics)) 
        || is.null(contrast))) {
        warnwrap("The creation of a biodist diagram requires statistical ",
            "testing! Removing from figures list...")
        qcPlots <- qcPlots[-which(qcPlots == "biodist")]
    }
    if ("volcano" %in% qcPlots && (any(is.na(statistics)) 
        || is.null(contrast))) {
        warnwrap("The creation of a volcano plot requires statistical ",
            "testing! Removing from figures list...")
        qcPlots <- qcPlots[-which(qcPlots == "volcano")]
    }
    if ("deheatmap" %in% qcPlots && (any(is.na(statistics)) 
        || is.null(contrast))) {
        warnwrap("The creation of a deheatmap plot requires statistical ",
            "testing! Removing from figures list...")
        qcPlots <- qcPlots[-which(qcPlots == "deheatmap")]
    }
    if ("statvenn" %in% qcPlots && (any(is.na(statistics)) 
        || is.null(contrast))) {
        warnwrap("The creation of a statvenn plot requires statistical ",
            "testing! Removing from figures list...")
        qcPlots <- qcPlots[-which(qcPlots == "statvenn")]
    }
    if ("foldvenn" %in% qcPlots && (any(is.na(statistics)) 
        || is.null(contrast))) {
        warnwrap("The creation of a foldvenn plot requires statistical ",
            "testing! Removing from figures list...")
        qcPlots <- qcPlots[-which(qcPlots == "foldvenn")]
    }
    if ("deregulogram" %in% qcPlots && (any(is.na(statistics)) 
        || is.null(contrast))) {
        warnwrap("The creation of a deregulogram plot requires statistical ",
            "testing! Removing from figures list...")
        qcPlots <- qcPlots[-which(qcPlots == "deregulogram")]
    }
    # mastat only if there is a contrast, otherwise nothing to plot
    if ("mastat" %in% qcPlots && is.null(contrast)) {
        warnwrap("The creation of a mastat plot requires the definition of a ",
            "contrast! Removing from figures list...")
        qcPlots <- qcPlots[-which(qcPlots == "mastat")]
    }
    # Check if drawing a Venn diagram among tests is possible
    if ("statvenn" %in% qcPlots && length(statistics)==1 
        && !any(is.na(statistics))) {
        warnwrap("The creation of a Venn diagram among different statistical ",
            "tests is possible only when more than\none statistical ",
            "algorithms are used! Removing from figures list...")
        qcPlots <- qcPlots[-which(qcPlots == "statvenn")]
    }
    # Check if drawing a Venn diagram among contrasts is possible
    if ("foldvenn" %in% qcPlots && !is.null(contrast) &&  length(contrast)==1) {
        warnwrap("The creation of a Venn diagram among different statistical ",
            "comparisons is possible only when more than\none contrast ",
            "defined! Removing from figures list...")
        qcPlots <- qcPlots[-which(qcPlots == "foldvenn")]
    }
    # Check if drawing a deregulogram for contrast pairs
    if ("deregulogram" %in% qcPlots && !is.null(contrast) 
        && length(contrast)==1) {
        warnwrap("The creation of a deregulogram for pairwise statistical ",
            "comparisons is possible only when more than\none contrast ",
            "defined! Removing from figures list...")
        qcPlots <- qcPlots[-which(qcPlots == "deregulogram")]
    }
    # Remove meandiff if there are no replicates 
    if ("meandiff" %in% qcPlots & any(lengths(sampleList) < 2)) {
        warnwrap("The creation of a meandiff plot is not possible for single ",
            "replicate conditions!\nRemoving from figures list...")
        qcPlots <- qcPlots[-which(qcPlots == "meandiff")]
    }
    # Remove rnacomp if there are more than 10 samples
    if ("rnacomp" %in% qcPlots & sum(lengths(sampleList)) > 12) {
        warnwrap("The creation of an rnacomp plot is not possible for more ",
            "than 12 samples!\nRemoving from figures list...")
        qcPlots <- qcPlots[-which(qcPlots == "rnacomp")]
    }
    # Check if we have single-replicate conditions and presence$perCondition is
    # enabled
    if (any(lengths(sampleList) < 2) & !is.null(geneFilters$presence)) {
        if (geneFilters$presence$perCondition) {
            warnwrap("geneFilters$presence$perCondition cannot be TRUE when ",
                "there are single-replicate conditions are present\nas this ",
                "will cause sample drops! Setting to FALSE...")
            geneFilters$presence$perCondition <- FALSE
        }        
    }
    # Check if tracks asked but we are in Windows...
    if (createTracks && .Platform$OS.type == "windows") {
        warnwrap("Signal tracks asked but Windows OS detected! Track ",
            "generation is not possible in Windows. Ignoring...")
        createTracks = FALSE
    }
    # Check if tracks asked but not starting with a targets file
    if (createTracks && is.null(theList)) {
        warnwrap("Signal tracks asked but no targets file with BAM file paths ",
            "provided! Ignoring...")
        createTracks <- FALSE
    }
    # Check if tracks asked but organism is not directly supported
    if (createTracks && !(org %in% getSupportedOrganisms()))
        warnwrap("Organism ",org," is not in the list of directly supported ",
            "organisms! If the pipeline fails, please use the\n",
            "createSignalTracks function directly.")
    
    # Check additional input arguments for normalization and statistics
    algArgs <- validateAlgArgs(normalization,statistics,normArgs,statArgs)
    normArgs <- algArgs$normArgs
    statArgs <- algArgs$statArgs
    
    # Override settings if a preset is given
    if (!is.null(preset)) {
        presetOpts <- getPresetOpts(preset,org)
        exonFilters <- presetOpts$exonFilters
        geneFilters <- presetOpts$geneFilters
        pcut <- presetOpts$pcut
        exportWhat <- presetOpts$exportWhat
        exportScale <- presetOpts$exportScale
        exportValues <- presetOpts$exportValues
        exportStats <- presetOpts$exportStats
    }

    if (report) {
        reportMessages <- makeReportMessages("en")
        if (!is.null(qcPlots) && !("png" %in% figFormat)) {
            warnwrap("png format is required in order to build a report! ",
                "Adding to figure output formats...")
            figFormat <- c(figFormat,"png")
        }
    }
    
    # Check for replicates. DESeq2 cannot perform without them and ABSSeq cannot
    # perform complex model analysis if not provided with replicates.
    if ("deseq2" %in% statistics && any(lengths(sampleList) < 2)) { 
        stopwrap("DESeq2 does not support analysis without ",
            "replication. Please choose another algorithm or ",
            "provide replicates.")
    }
    
    if (!is.null(contrast) && "absseq" %in% statistics) {        
        contrastListRepCheck <- makeContrastList(contrast,sampleList)
        for (conName in names(contrastListRepCheck)) {
            con <- contrastListRepCheck[[conName]]
            cons <- unique(unlist(con))
            # Checking if we have more than 2 conditions to compare 
            # simultaneously
            if (length(cons)>2) {
                if (any(lengths(sampleList) < 2))
                    # Checking if there are no replicates
                    stopwrap("ABSSeq cannot perform complex design",
                        "analysis without replicates.")
            }
        }
    }
    
    # Display initialization report
    TB <- Sys.time()
    disp(strftime(Sys.time()),": Data processing started...\n")
    ############################################################################
    if ("dss" %in% statistics && any(lengths(sampleList) < 2)) {
        message=c(
            "\n=================================================\n", 
            "DSS will be run without replicates.\n",
            "Results must be interpreted with caution.\n",
            "===================================================\n"
        )
        disp(message)
    }
    
    disp("Read counts file: ",countsName)
    disp("Conditions: ",paste(names(sampleList),collapse=", "))
    disp("Samples to include: ",paste(unlist(sampleList),collapse=", "))
    if (!is.null(excludeList) && !is.na(excludeList))
        disp("Samples to exclude: ",paste(unlist(excludeList),collapse=", "))
    else
        disp("Samples to exclude: none")
    if (!is.null(contrast))
        disp("Requested contrasts: ",paste(contrast,collapse=", "))
    else
        disp("Requested contrasts: none")
    if (!is.null(libsizeList)) {
        disp("Library sizes: ")
        for (n in names(libsizeList))
            disp("  ",paste(n,libsizeList[[n]],sep=": "))
    }
    if (!is.null(annotation) && !is.list(annotation))
        disp("Annotation: ",annotation)
    if (is.list(annotation))
        disp("Annotation: user provided GTF file")
    disp("Organism: ",org)
    disp("Reference source: ",refdb)
    disp("Count type: ",countType)
    if (countType == "utr") {
        disp("3' UTR fraction: ",utrOpts$frac)
        disp("3' UTR minimum length: ",utrOpts$minLength,"bps")
        disp("3' UTR downstream: ",utrOpts$downstream,"bps")
    }
    if (!is.null(preset))
        disp("Analysis preset: ",preset)
    disp("Transcriptional level: ",transLevel)
    if (!is.null(exonFilters)) {
        disp("Exon filters: ",paste(names(exonFilters),collapse=", "))
        for (ef in names(exonFilters)) {
            disp("  ",ef,": ")
            for (efp in names(exonFilters[[ef]])) {
                if (length(exonFilters[[ef]][[efp]])==1 && 
                    is.function(exonFilters[[ef]][[efp]]))
                    print(exonFilters[[ef]][[efp]])
                else if (length(exonFilters[[ef]][[efp]])==1)
                    disp("    ",paste(efp,exonFilters[[ef]][[efp]],sep=": "))
                else if (length(exonFilters[[ef]][[efp]])>1)
                    disp("    ",paste(efp,paste(exonFilters[[ef]][[efp]],
                        collapse=", "),sep=": "))
            }
        }
    }
    else
        disp("Exon filters: none applied")
    if (!is.null(geneFilters)) {
        disp("Gene filters: ",paste(names(geneFilters),collapse=", "))
        for (gf in names(geneFilters)) {
            disp("  ",gf,": ")
            for (gfp in names(geneFilters[[gf]])) {
                if (length(geneFilters[[gf]][[gfp]])==1 && 
                    is.function(geneFilters[[gf]][[gfp]]))
                    print(geneFilters[[gf]][[gfp]])
                else if (length(geneFilters[[gf]][[gfp]])==1)
                    disp("    ",paste(gfp,geneFilters[[gf]][[gfp]],sep=": "))
                else if (length(geneFilters[[gf]][[gfp]])>1)
                    disp("    ",paste(gfp,paste(geneFilters[[gf]][[gfp]],
                        collapse=", "),sep=": "))
            }
        }
    }
    else
        disp("Gene filters: none applied")
    disp("Filter application: ",whenApplyFilter)
    disp("Normalization algorithm: ",normalization)
    if (!is.null(normArgs)) {
        disp("Normalization arguments: ")
        for (na in names(normArgs)) {
            if (length(normArgs[[na]])==1 && is.function(normArgs[[na]])) {
                disp("  ",na,": ")
                disp(as.character(substitute(normArgs[[na]])))
            }
            else if (length(normArgs[[na]])==1)
                disp("  ",paste(na,normArgs[[na]],sep=": "))
            else if (length(normArgs[[na]])>1)
                disp("  ",paste(na,paste(normArgs[[na]],collapse=", "),
                    sep=": "))
        }
    }
    if (!any(is.na(statistics)))
        disp("Statistical algorithm(s): ",paste(statistics,collapse=", "))
    else
        disp("Statistical algorithm(s): no testing selected")
    if (!is.null(statArgs)) {
        if (!any(is.na(statistics))) {
            disp("Statistical arguments: ")
            for (sa in names(statArgs)) {
                if (length(statArgs[[sa]])==1 && is.function(statArgs[[sa]])) {
                    disp("  ",sa,": ")
                    disp(as.character(substitute(statArgs[[na]])))
                }
                else if (length(statArgs[[sa]])==1)
                    disp("  ",paste(sa,statArgs[[sa]],sep=": "))
                else if (length(statArgs[[sa]])>1)
                    disp("  ",paste(sa,paste(statArgs[[sa]],collapse=", "),
                        sep=": "))
            }
        }
        else
            disp("Statistical arguments: no testing selected")
    }
    disp("Meta-analysis method: ",metaP)
    disp("Multiple testing correction: ",adjustMethod)
    if (!is.na(pcut)) 
        disp("p-value threshold: ",pcut)
    disp("Logarithmic transformation offset: ",logOffset)
    if (!is.null(preset)) 
        disp("Analysis preset: ",preset)
    disp("Quality control plots: ",paste(qcPlots,collapse=", "))
    disp("Figure format: ",paste(figFormat,collapse=", "))
    if (!is.na(exportWhere)) 
        disp("Output directory: ",exportWhere)
    disp("Output data: ",paste(exportWhat,collapse=", "))
    disp("Output scale(s): ",paste(exportScale,collapse=", "))
    disp("Output values: ",paste(exportValues,collapse=", "))
    if ("stats" %in% exportWhat)
        disp("Output statistics: ",paste(exportStats,collapse=", "),"\n")
        
    if (is.function(.progressFun)) {
        text <- paste("Starting the analysis...")
        .progressFun(detail=text)
    }
    ############################################################################
    
    # geneData are always required, unless annotation is embedded, where we
    # need only geneData as embedded annotation is not allowed anywhere else
    disp("Loading gene annotation...")
    if (!is.null(annotation) && annotation == "embedded") {
        # The following should work if annotation elements are arranged 
        # in MeV-like data style
        if (!is.data.frame(counts)) {
            disp("Reading counts file ",countsName,"...")
            geneCounts <- read.delim(counts)
        }
        else
            geneCounts <- counts
        rownames(geneCounts) <- as.character(geneCounts[,embedCols$idCol])
        allCols <- seq_len(ncol(geneCounts))
        samCols <- match(unlist(sampleList),colnames(geneCounts))
        samCols <- samCols[which(!is.na(samCols))]
        annCols <- allCols[-samCols]
        geneData <- geneCounts[,annCols]
        geneCounts <- geneCounts[,samCols]      
        colnames(geneData)[embedCols$idCol] <- "gene_id"
        if (!is.na(embedCols$gcCol)) {
            colnames(geneData)[embedCols$gcCol] <- "gc_content"
            if (max(geneData$gc_content<=1)) # Is already divided
                geneData$gc_content = 100*geneData$gc_content
        }
        if (!is.na(embedCols$nameCol)) 
            colnames(geneData)[embedCols$nameCol] <- "gene_name"
        if (!is.na(embedCols$btCol))
            colnames(geneData)[embedCols$btCol] <- "biotype"
        geneData <- GRanges(geneData)
        names(geneData) <- geneData$gene_id
        
        # Remove saturation if no biotypes
        if ("saturation" %in% qcPlots && (is.na(embedCols$btCol) 
            || length(unique(geneData$biotype)) == 1)) {
            warnwrap("The creation of an saturation plots is available for ",
                "more than one biotype!\nRemoving from figures list...")
            qcPlots <- qcPlots[-which(qcPlots == "saturation")]
        }
    }
    else {
        geneData <- tryCatch(loadAnnotation(org,refdb,level=transLevel,
            type="gene",version=version,db=localDb,rc=restrictCores),
            error=function(e) {
                # Not found and user based
                if (!is.null(annotation)) { # Has been checked
                    gtfFile <- annotation$gtf
                    metadata <- annotation
                    metadata$gtf <- NULL
                    geneData <- importCustomAnnotation(gtfFile,metadata,
                        "gene","gene")
                }
                else
                    stop("Please provide an existing organism or a list ",
                        "with annotation metadata and GTF file!")
            },finally="")
        
        # Remove saturation if no biotypes
        if ("saturation" %in% qcPlots && length(unique(geneData$biotype))==1) {
            warnwrap("The creation of an saturation plots is available for ",
                "more than one biotype!\nRemoving from figures list...")
            qcPlots <- qcPlots[-which(qcPlots == "saturation")]
        }
    }
    
    # Now start examining additional required data per case...
    if (countType=="exon") {
        # We need to load the exon annotation and see what counts have been
        # provided
        if (!fromPrevious) {
            # Load exon annotation
            disp("Loading exon annotation...")
            exonData <- tryCatch(loadAnnotation(org,refdb,level=transLevel,
                type=countType,version=version,db=localDb,summarized=TRUE,
                rc=restrictCores),
            error=function(e) {
                # Not found and user based
                if (!is.null(annotation)) { # Has been checked
                    gtfFile <- annotation$gtf
                    metadata <- annotation
                    metadata$gtf <- NULL
                    exonData <- importCustomAnnotation(gtfFile,metadata,
                        "gene","exon")
                }
                else
                    stop("Please provide an existing organism or a list ",
                        "with annotation metadata and GTF file!")
            },finally="")
            
            # Load/read counts
            if (!is.null(counts)) { # Provided
                if (!is.data.frame(counts) && !is.list(counts)) {
                    disp("Reading counts file ",countsName,"...")
                    exonCounts <- read.delim(counts,row.names=1)

                    ## Re-arrange columns to be in consistency with colData
                    ## used in statDeseq2
                    exonCounts <- exonCounts[,unlist(sampleList,
                        use.names=FALSE),drop=FALSE]
                }
                else { # Already a data frame as input
                    if (is.character(counts[,1])) {
                        exonCounts <- as.matrix(counts[,-1])
                        rownames(exonCounts) <- as.character(counts[,1])

                        ## Re-arrange columns to be in consistency with colData
                        ## used in statDeseq2
                        exonCounts <- exonCounts[,unlist(sampleList,
                            use.names=FALSE),drop=FALSE]
                    }
                    else { # Should be named!
                        if (is.null(rownames(counts)))
                            stopwrap("A counts data frame as input should ",
                                "have rownames!")
                        exonCounts <- counts

                        ## Re-arrange columns to be in consistency with colData
                        ## used in statDeseq2
                        exonCounts <- exonCounts[,unlist(sampleList,
                            use.names=FALSE),drop=FALSE]
                    }
                }
            }
            else { # Coming from read2count
                if (fromRaw) { # Double check
                    r2c <- read2count(theList,exonData,fileType,utrOpts,
                        rc=restrictCores)
                    exonCounts <- r2c$counts
                    # Merged exon data! - Not needed anymore
                    #exonData <- r2c$mergedann
                    if (is.null(libsizeList))
                        libsizeList <- r2c$libsize
                    if (exportCountsTable) {
                        exonDataExp <- as.data.frame(exonData)
                        exonDataExp <- exonDataExp[,c(1,2,3,6,7,5,8,9)]
                        names(exonDataExp)[1] <- "chromosome"
                        disp("Exporting raw read counts table to ",
                            file.path(PROJECT_PATH[["lists"]],
                                "raw_counts_table.txt.gz"))
                        resFile <- file.path(PROJECT_PATH[["lists"]],
                            "raw_counts_table.txt.gz")
                        gzfh <- gzfile(resFile,"w")
                        write.table(cbind(
                            exonDataExp[rownames(exonCounts),],
                            exonCounts
                        ),gzfh,sep="\t",row.names=FALSE,quote=FALSE)
                        close(gzfh)
                    }
                }
            }
            exonCounts <- exonCounts[,unlist(sampleList,use.names=FALSE)]

            # Get the exon counts per gene model
            disp("Checking chromosomes in exon counts and gene annotation...")
            geneData <- .reduceGeneData(exonData[rownames(exonCounts)],geneData)
            exonData <- .reduceGeneData(exonData[rownames(exonCounts)],exonData)
            disp("Processing exons...")
            theCounts <- constructGeneModel(exonCounts,exonData,type="exon",
                rc=restrictCores)

            if (saveGeneModel) {
                disp("Saving gene model to ",file.path(PROJECT_PATH[["data"]],
                    "gene_model.RData"))
                save(theCounts,exonData,geneData,sampleList,transLevel,
                    countType,file=file.path(PROJECT_PATH$data,
                    "gene_model.RData"),compress=TRUE)
            }
        }
        else {
            theCounts <- tmpEnv$theCounts
            exonData <- tmpEnv$exonData
            geneData <- tmpEnv$geneData
        }

        # Exclude any samples not wanted (when e.g. restoring a previous project
        # and having determined that some samples are of bad quality
        if (!is.null(excludeList) && !is.na(excludeList)) {
            for (n in names(excludeList)) {
                sampleList[[n]] <- setdiff(sampleList[[n]],
                    excludeList[[n]])
                if (length(sampleList[[n]])==0) # Removed whole condition
                    sampleList[n] <- NULL
            }
            # Attributes are lost when subsetting
            # https://cran.r-project.org/web/packages/sticky/
            #vignettes/introduction.html
            theCounts <- .excludeSamplesFromList(theCounts,
                unlist(sampleList,use.names=FALSE))
        }
        
        # Apply exon filters
        if (!is.null(exonFilters)) {
            exonFilterOut <- filterExons(theCounts,geneData,sampleList,
                exonFilters)
            exonFilterResult <- exonFilterOut$result
            exonFilterFlags <- exonFilterOut$flags
        }
        else
            exonFilterResult <- exonFilterFlags <- NULL
        
        disp("Summarizing count data...")
        theGeneCounts <- theExonLengths <- vector("list",
            length(unlist(sampleList)))
        names(theGeneCounts) <- names(theExonLengths) <- names(theCounts)
        for (n in names(theGeneCounts))
            theGeneCounts[[n]] <- vapply(theCounts[[n]],sum,numeric(1))
        geneCounts <- do.call("cbind",theGeneCounts)
        # Based on the sum of their exon lengths
        lengthList <- attr(theCounts,"lengthList")
        geneLength <- vapply(lengthList,sum,numeric(1))
        # Could also be
        # geneLength <- attr(exonData,"activeLength")
        
        # In case there are small differences between annotation data and  
        # external file, due to e.g. slightly different Ensembl versions
        geneData <- geneData[rownames(geneCounts)]
        totalGeneData <- geneData # We need this for some total stats
    }
    
    if (countType=="utr") {
        # We need to load the utr annotation and see what counts have been
        # provided
        if (!fromPrevious) {
            disp("Loading 3' UTR annotation...")
            transcriptData <- tryCatch(loadAnnotation(org,refdb,
                level=transLevel,type=countType,version=version,db=localDb,
                summarized=TRUE,rc=restrictCores),error=function(e) {
                # Not found and user based
                if (!is.null(annotation)) { # Has been checked
                    gtfFile <- annotation$gtf
                    metadata <- annotation
                    metadata$gtf <- NULL
                    transcriptData <- importCustomAnnotation(gtfFile,metadata,
                        transLevel,countType)
                }
                else
                    stop("Please provide an existing organism or a list with ",
                        "annotation metadata and GTF file!")
            },finally="")
            
            # Load/read counts
            if (!is.null(counts)) { # Otherwise coming ready from read2count
                if (!is.data.frame(counts) && !is.list(counts)) {
                    disp("Reading counts file ",countsName,"...")
                    transcriptCounts <- read.delim(counts, row.names=1)

                    ## Re-arrange columns to be in consistency with colData
                    ## used in statDeseq2
                    transcriptCounts <- transcriptCounts[,unlist(sampleList,
                        use.names= FALSE)]
                }
                else { # Already a data frame as input
                    if (is.character(counts[,1])) {
                        transcriptCounts <- as.matrix(counts[,-1])
                        rownames(transcriptCounts) <- as.character(counts[,1])

                        ## Re-arrange columns to be in consistency with colData
                        ## used in statDeseq2
                        transcriptCounts <- transcriptCounts[,unlist(sampleList,
                            use.names=FALSE),drop=FALSE]
                    }
                    else { # Should be named!
                        if (is.null(rownames(counts)))
                            stopwrap("A counts data frame as input should ",
                                "have rownames!")
                        transcriptCounts <- counts

                        ## Re-arrange columns to be in consistency with colData
                        ## used in statDeseq2
                        transcriptCounts <- transcriptCounts[,unlist(sampleList,
                            use.names=FALSE),drop=FALSE]
                    }
                }
            }
            else { # Coming from read2count
                if (fromRaw) { # Double check
                    r2c <- read2count(theList,transcriptData,fileType,
                        transLevel,utrOpts,rc=restrictCores)
                    transcriptCounts <- r2c$counts
                    if (is.null(libsizeList))
                        libsizeList <- r2c$libsize
                    if (exportCountsTable) {
                        transcriptDataExp <- as.data.frame(transcriptData)
                        transcriptDataExp <- 
                            transcriptDataExp[,c(1,2,3,6,7,5,8,9)]
                        names(transcriptDataExp)[1] <- "chromosome"
                        disp("Exporting raw read counts table to ",
                            file.path(PROJECT_PATH[["lists"]],
                            "raw_counts_table.txt.gz"))
                        resFile <- file.path(PROJECT_PATH[["lists"]],
                            "raw_counts_table.txt.gz")
                        gzfh <- gzfile(resFile,"w")
                        write.table(cbind(
                            transcriptDataExp[rownames(transcriptCounts),],
                            transcriptCounts
                        ),gzfh,sep="\t",row.names=FALSE,quote=FALSE)
                        close(gzfh)
                    }
                }
            }
            transcriptCounts <- transcriptCounts[,unlist(sampleList,
                use.names=FALSE)]

            # Get the transcript counts per gene model
            disp("Checking chromosomes in transcript counts and gene ",
                "annotation...")
            geneData <- 
                .reduceGeneData(transcriptData[rownames(transcriptCounts)],
                    geneData)
            transcriptData <- 
                .reduceGeneData(transcriptData[rownames(transcriptCounts)],
                    transcriptData)
            disp("Processing transcripts...")
            theCounts <- constructGeneModel(transcriptCounts,transcriptData,
                type="utr",rc=restrictCores)
            
            if (saveGeneModel) {
                disp("Saving gene model to ",file.path(PROJECT_PATH[["data"]],
                    "gene_model.RData"))
                save(theCounts,transcriptData,geneData,sampleList,countType,
                    transLevel,file=file.path(PROJECT_PATH$data,
                    "gene_model.RData"),compress=TRUE)
            }
        }
        else {
            theCounts <- tmpEnv$theCounts
            transcriptData <- tmpEnv$transcriptData
            geneData <- tmpEnv$geneData
        }

        # Exclude any samples not wanted (when e.g. restoring a previous project
        # and having determined that some samples are of bad quality
        if (!is.null(excludeList) && !is.na(excludeList)) {
            for (n in names(excludeList)) {
                sampleList[[n]] <- setdiff(sampleList[[n]],
                    excludeList[[n]])
                if (length(sampleList[[n]])==0) # Removed whole condition
                    sampleList[n] <- NULL
            }
            #theCounts <- theCounts[unlist(sampleList)]
            theCounts <- .excludeSamplesFromList(theCounts,
                unlist(sampleList,use.names=FALSE))
        }
        
        disp("Summarizing count data...")
        theGeneCounts <- theTranscriptLengths <- vector("list",
            length(unlist(sampleList)))
        names(theGeneCounts) <- names(theTranscriptLengths) <- 
            names(theCounts)
        for (n in names(theGeneCounts))
            theGeneCounts[[n]] <- vapply(theCounts[[n]],sum,numeric(1))
        geneCounts <- do.call("cbind",theGeneCounts)
        # Based on the sum of their transcript lengths
        lengthList <- attr(theCounts,"lengthList")
        geneLength <- vapply(lengthList,sum,numeric(1))
        # Could also be
        # geneLength <- attr(transcriptData,"activeLength")
        
        # In case there are small differences between annotation data and 
        # external file, due to e.g. slightly different Ensembl versions
        geneData <- geneData[rownames(geneCounts),]
        totalGeneData <- geneData # We need this for some total stats
        
        # No exon filters have been applied, we are at "utr" level
        exonFilterResult <- NULL
    }
    
    else if (countType=="gene") {
        # geneData has already been loaded and also geneCounts in the case of
        # embedded annotation
        if (!fromPrevious) {
            # Load/read counts
            if (!is.null(counts)  && !is.list(counts)) {
                if (!is.data.frame(counts)) { # Else it's already here
                    disp("Reading counts file ",countsName,"...")
                    geneCounts <- read.delim(counts, row.names= 1)

                    ## Re-arrange columns to be in consistency with colData
                    ## used in statDeseq2
                    geneCounts <- geneCounts[,unlist(sampleList,
                        use.names=FALSE),drop=FALSE]
                }
                else { # Already a data frame as input
                    if (is.character(counts[,1])) {
                        geneCounts <- as.matrix(counts[,-1])
                        rownames(geneCounts) <- as.character(counts[,1])

                        ## Re-arrange columns to be in consistency with colData
                        ## used in statDeseq2
                        geneCounts <- geneCounts[,unlist(sampleList,
                            use.names=FALSE),drop=FALSE]
                    }
                    else { # Should be named!
                        if (is.null(rownames(counts)))
                            stopwrap("A counts data frame as input should ",
                                "have rownames!")
                        geneCounts <- counts

                        ## Re-arrange columns to be in consistency with colData
                        ## used in statDeseq2
                        geneCounts <- geneCounts[,unlist(sampleList,
                            use.names=FALSE),drop=FALSE]
                    }
                }
            }
            else { # Coming from read2count
                if (fromRaw) { # Double check
                    r2c <- read2count(theList,geneData,fileType,
                        utrOpts,rc=restrictCores)
                    geneCounts <- r2c$counts
                    if (is.null(libsizeList))
                        libsizeList <- r2c$libsize
                    if (exportCountsTable) {
                        geneDataExp <- as.data.frame(geneData)
                        geneDataExp <- geneDataExp[,c(1,2,3,6,7,5,8,9)]
                        names(geneDataExp)[1] <- "chromosome"
                        disp("Exporting raw read counts table to ",
                            file.path(PROJECT_PATH[["lists"]],
                            "raw_counts_table.txt.gz"))
                        resFile <- file.path(PROJECT_PATH[["lists"]],
                            "raw_counts_table.txt.gz")
                        gzfh <- gzfile(resFile,"w")
                        write.table(cbind(
                            geneDataExp[rownames(geneCounts),],
                            geneCounts
                        ),gzfh,sep="\t",row.names=FALSE,quote=FALSE)
                        close(gzfh)
                    }
                }
            }
        }
        else {
            geneCounts <- tmpEnv$geneCounts
            geneData <- tmpEnv$geneData
        }
        
        totalGeneData <- geneData # We need this for some total stats
        exonFilterResult <- NULL

        gValid <- intersect(rownames(geneCounts), geneData$gene_id)
        geneCounts <- geneCounts[gValid,]

        geneData <- geneData[rownames(geneCounts)]
        geneLength <- width(geneData)
        names(geneLength) <- names(geneData)
        
        if (saveGeneModel) {
            disp("Saving gene model to ",file.path(PROJECT_PATH[["data"]],
                "gene_model.RData"))
            save(geneCounts,geneData,sampleList,countType,
                file=file.path(PROJECT_PATH$data,"gene_model.RData"),
                compress=TRUE)
        }
        
        # Exclude any samples not wanted (when e.g. restoring a previous project
        # and having determined that some samples are of bad quality
        if (!is.null(excludeList) && !is.na(excludeList)) {
            for (n in names(excludeList)) {
                sampleList[[n]] <- setdiff(sampleList[[n]],
                    excludeList[[n]])
                if (length(sampleList[[n]])==0) # Removed whole condition
                    sampleList[n] <- NULL
            }
            geneCounts <- geneCounts[,unlist(sampleList,use.names=FALSE)]
        }
    }

    # Transform GC-content and biotype - should never be required in the new
    # annotation strategy
    if (is.null(geneData$gc_content))
        geneData$gc_content <- rep(0.5,length(geneData))
    if (is.null(geneData$biotype))
        geneData$biotype <- rep("gene",length(geneData))
    
    names(geneLength) <- rownames(geneCounts)
    attr(geneData,"geneLength") <- geneLength

    ############################################################################
    # BEGIN FILTERING SECTION
    ############################################################################
    
    if (is.function(.progressFun)) {
        text <- paste("Filtering...")
        .progressFun(detail=text)
    }
    
    # GC bias is NOT alleviated if we do not remove the zeros!!!
    disp("Removing genes with zero counts in all samples...")
    theZeros <- which(apply(geneCounts,1,filterLow,0))
    if (length(theZeros) > 0) {
        # Store the filtered, maybe we do some stats
        geneCountsZero <- geneCounts[theZeros,,drop=FALSE]
        geneDataZero <- geneData[theZeros]
        attr(geneDataZero,"geneLength") <- geneLength[theZeros]
        theZeroNames <- names(geneData)[theZeros]
        # Then remove
        geneCounts <- geneCounts[-theZeros,,drop=FALSE]
        geneData <- geneData[-theZeros]
        attr(geneData,"geneLength") <- geneLength[-theZeros]
    }
    else
        geneCountsZero <- geneDataZero <- theZeroNames <- NULL

    # Store un-normalized gene counts for export purposes
    geneCountsUnnorm <- geneCounts

    # Apply filtering prior to normalization if desired
    if (whenApplyFilter=="prenorm") {
        # However, a first round of normalization has to be performed in
        # order to get proper expression filters
        disp("Prefiltering normalization with: ",normalization)
        switch(normalization,
            edaseq = {
                tempGenes <- normalizeEdaseq(geneCounts,sampleList,
                    normArgs,geneData,output="matrix")
            },
            deseq = {
                tempGenes <- normalizeDeseq(geneCounts,sampleList,normArgs,
                    output="matrix")
            },
            deseq2 = {
                tempGenes <- normalizeDeseq2(geneCounts,sampleList,normArgs,
                    output="matrix")
            },   
            edger = {
                tempGenes <- normalizeEdger(geneCounts,sampleList,normArgs,
                    output="matrix")
            },
            noiseq = {  
                tempGenes <- normalizeNoiseq(geneCounts,sampleList,
                    normArgs,geneData,logOffset,output="matrix")
            },
            nbpseq = {
                tempGenes <- normalizeNbpseq(geneCounts,sampleList,
                    normArgs,libsizeList,output="matrix")
            },
            absseq = {
                tempGenes <- normalizeAbsseq(geneCounts,sampleList,normArgs,
                    output="matrix")
            },
            dss = {
                tempGenes <- normalizeDss(geneCounts,sampleList,normArgs,
                    output="native")
            },
            none = {
                # In case some external normalization is applied (e.g. equal
                # read counts from all samples)
                tempGenes <- geneCounts
            }
        )
        
        # Now filter
        if (!is.null(geneFilters)) {
            geneFilterOut <- filterGenes(tempGenes,geneData,geneFilters,
                sampleList)
            geneFilterResult <- geneFilterOut$result
            geneFilterCutoff <- geneFilterOut$cutoff
            geneFilterFlags <- geneFilterOut$flags
        }
        else
            geneFilterResult <- geneFilterCutoff <- geneFilterFlags <- NULL

        # Unify the filters and filter
        theDeadGenes <- list(
            geneFilterResult$expression$median,
            geneFilterResult$expression$mean,
            geneFilterResult$expression$quantile,
            geneFilterResult$expression$known,
            geneFilterResult$expression$custom
        )
        theDead <- unique(unlist(c(geneFilterResult,exonFilterResult)))
        # Some genes filtered by zero, were present in exon filters, not yet 
        # applied
        if (countType=="exon")
            theDead <- setdiff(theDead,theZeroNames)
        
        # All method specific objects are row-index subsettable
        if (length(theDead)>0) {
            # Store the filtered for later export or some stats
            geneCountsDead <- geneCounts[theDead,]
            geneCountsUnnorm <- geneCountsUnnorm[theDead,]
            geneDataDead <- geneData[theDead]
            attr(geneDataDead,"geneLength") <- attr(geneData,
                "geneLength")[theDead]
            # Now filter
            theDeadInd <- match(theDead,rownames(geneCounts))
            geneCountsExpr <- geneCounts[-theDeadInd,]
            geneDataExpr <- geneData[-theDeadInd]
            attr(geneDataExpr,"geneLength") <- attr(geneData,
                "geneLength")[-theDeadInd]
        }
        else {
            geneCountsExpr <- geneCounts
            geneDataExpr <- geneData
            geneCountsDead <- geneDataDead <- geneCountsUnnorm <- NULL
        }
        
        if (is.function(.progressFun)) {
            text <- paste("Normalizing...")
            .progressFun(detail=text)
        }
        
        disp("Normalizing with: ",normalization)
        switch(normalization,
            edaseq = {
                normGenes <- normalizeEdaseq(geneCountsExpr,sampleList,normArgs,
                    geneDataExpr,output="matrix")
            },
            deseq = {
                normGenes <- normalizeDeseq(geneCountsExpr,sampleList,normArgs,
                    output="native")
            },
            deseq2 = {
                normGenes <- normalizeDeseq2(geneCountsExpr,sampleList,normArgs,
                    output="native")
            },
            edger = {
                normGenes <- normalizeEdger(geneCountsExpr,sampleList,normArgs,
                    output="native")
            },
            noiseq = {
                normGenes <- normalizeNoiseq(geneCountsExpr,sampleList,normArgs,
                    geneDataExpr,logOffset,output="matrix")
            },
            nbpseq = {
                normGenes <- normalizeNbpseq(geneCountsExpr,sampleList,normArgs,
                    libsizeList,output="native")
            },
            absseq = {
                normGenes <- normalizeAbsseq(geneCountsExpr,sampleList,normArgs,
                    output="native")
            },
            dss = {
                normGenes <- normalizeDss(geneCountsExpr,sampleList,normArgs,
                    output="native")
            },   
            none = {
                normGenes <- geneCountsExpr
            }
        )
        normGenesExpr <- normGenes
    }
    else if (whenApplyFilter=="postnorm") {
        if (is.function(.progressFun)) {
            text <- paste("Normalizing...")
            .progressFun(detail=text)
        }
        
    # Apply filtering after normalization if desired (default)
    disp("Normalizing with: ",normalization)   
        switch(normalization,
            edaseq = {
                normGenes <- normalizeEdaseq(geneCounts,sampleList,
                    normArgs,geneData,output="matrix")
            },
            deseq = {
                normGenes <- normalizeDeseq(geneCounts,sampleList,normArgs,
                    output="native")
            },
            deseq2 = {
                normGenes <- normalizeDeseq2(geneCounts,sampleList,
                    normArgs,output="native")
            },
            edger = {
                normGenes <- normalizeEdger(geneCounts,sampleList,normArgs,
                    output="native")
            },
            noiseq = {
                normGenes <- normalizeNoiseq(geneCounts,sampleList,
                    normArgs,geneData,logOffset,output="matrix")
            },
            nbpseq = {
                normGenes <- normalizeNbpseq(geneCounts,sampleList,
                    normArgs,libsizeList,output="native")
            },
            absseq = {
                normGenes <- normalizeAbsseq(geneCounts,sampleList,
                    normArgs,output="native")
            },
            dss = {
                normGenes <- normalizeDss(geneCounts,sampleList,normArgs,
                    output="native")
            },
            none = {
                normGenes <- geneCounts
            }
        )
        
        switch(class(normGenes)[1], 
            .CountDataSet = { # Has been normalized with DESeq
                #tempMatrix <- round(DESeq::counts(normGenes,normalized=TRUE))
                tempMatrix <- round(counts(normGenes,normalized=TRUE))
            },
            DESeqDataSet = { # Has been normalized with DESeq2
                tempMatrix <- round(DESeq2::counts(normGenes,normalized=TRUE))
            },
            DGEList = { # Has been normalized with edgeR
                # Trick found at http://cgrlucb.wikispaces.com/edgeR+spring2013
                scl <- normGenes$samples$lib.size *
                    normGenes$samples$norm.factors
                tempMatrix <- round(t(t(normGenes$counts)/scl)*mean(scl))
            },
            matrix = { # Has been normalized with EDASeq or NOISeq or nothing
                tempMatrix <- normGenes
            },
            data.frame = { # Has been normalized with or nothing
                tempMatrix <- as.matrix(normGenes)
            },
            nbData = { # Has been normalized with NBPSeq and main was "nbpseq"
                tempMatrix <- as.matrix(round(sweep(normGenes$counts,2,
                    normGenes$norm.factors,"*")))
            },
            nbp = { # Has been normalized with NBPSeq and main was "nbsmyth"
                tempMatrix <- as.matrix(round(normGenes$pseudo.counts))
            },
            ABSDataSet = { # Has been normalized with ABSSeq
                tempMatrix <- as.matrix(round(excounts(normGenes)))
            },
            SeqCountSet = { # Has been normalized with DSS
                # Dribble for taking a mtx out of SeqCountSet class
                classes <- asClassVector(sampleList)
                theDesign <- data.frame(condition=classes,
                    row.names=colnames(normGenes)) 
                cds <- newCountDataSet(as.matrix(round(
                    assayData(normGenes)$exprs)),theDesign$condition)
                #DESeq::sizeFactors(cds) <- normalizationFactor(normGenes)
                sizeFactors(cds) <- normalizationFactor(normGenes)
                #tempMatrix <- as.matrix(round(DESeq::counts(cds,
                #    normalized=TRUE)))
                tempMatrix <- as.matrix(round(counts(cds,normalized=TRUE)))
            }
        )

        # Implement gene filters after normalization
        if (!is.null(geneFilters)) {
            geneFilterOut <- filterGenes(tempMatrix,geneData,geneFilters,
                sampleList)
            geneFilterResult <- geneFilterOut$result
            geneFilterCutoff <- geneFilterOut$cutoff
            geneFilterFlags <- geneFilterOut$flags
        }
        else
            geneFilterResult <- geneFilterCutoff <-
                geneFilterFlags <- NULL

        # Unify the filters and filter
        theDeadGenes <- list(
            geneFilterResult$expression$median,
            geneFilterResult$expression$mean,
            geneFilterResult$expression$quantile,
            geneFilterResult$expression$known,
            geneFilterResult$expression$custom
        )
        #when running maually exonFilterResult=NULL
        theDead <- unique(unlist(c(geneFilterResult,exonFilterResult)))
        # Some genes filtered by zero, were present in exon filters, not yet 
        # applied
        if (countType=="exon")
            theDead <- setdiff(theDead,theZeroNames)
        
        # All method specific objects are row-index subsettable
        if (length(theDead) > 0) {
            # Store the filtered for later export or some stats
            geneCountsDead <- tempMatrix[theDead,]
            geneCountsUnnorm <- geneCountsUnnorm[theDead,]
            geneDataDead <- geneData[theDead]
            attr(geneDataDead,"geneLength") <- attr(geneData,
                "geneLength")[theDead]
            # Now filter
            theDeadInd <- match(theDead,rownames(tempMatrix))  
            switch(class(normGenes)[1],                           
                .CountDataSet = { # Has been normalized with DESeq
                    normGenesExpr <- normGenes[-theDeadInd,]
                },
                DESeqDataSet = { # Has been normalized with DESeq2
                    normGenesExpr <- normGenes[-theDeadInd,]
                },
                DGEList = { # edgeR bug???
                    normGenesExpr <- normGenes[-theDeadInd,]
                    normGenesExpr$AveLogCPM <-
                        normGenesExpr$AveLogCPM[-theDeadInd]
                },
                matrix = { # Has been normalized with EDASeq or NOISeq
                    normGenesExpr <- normGenes[-theDeadInd,]
                },
                data.frame = { # Has been normalized with EDASeq or NOISeq
                    normGenesExpr <- as.matrix(normGenes[-theDeadInd,])
                },
                nbData = { # Has been normalized NBPSeq, main.method="nbpseq"
                    normGenesExpr <- normGenes
                    normGenesExpr$counts <-
                        as.matrix(normGenesExpr$counts[-theDeadInd,])
                    normGenesExpr$rel.frequencies <- 
                        normGenesExpr$rel.frequencies[-theDeadInd,]
                    normGenesExpr$tags <-
                        as.matrix(normGenesExpr$tags[-theDeadInd,])
                },
                nbp = {
                    normGenesExpr <- normGenes
                    normGenesExpr$counts <-
                        as.matrix(normGenesExpr$counts[-theDeadInd,])
                    normGenesExpr$pseudo.counts <- 
                        as.matrix(normGenesExpr$pseudo.counts[-theDeadInd,])
                    normGenesExpr$pseudo.libSizes <- 
                        colSums(as.matrix(normGenesExpr$pseudo.counts))*
                            rep(1,dim(normGenesExpr$counts)[2])
                },
                ABSDataSet = { 
                    normGenesExpr <- normGenes
                    ABSSeq::counts(normGenesExpr) <-
                        ABSSeq::counts(normGenesExpr)[-theDeadInd,]
                    excounts(normGenesExpr) <-
                        excounts(normGenesExpr)[-theDeadInd,]
                },
                SeqCountSet = { 
                    normGenesExpr <- normGenes
                    # Subset raw counts table
                    normGenesExpr <- normGenesExpr[-theDeadInd,] 
                    # All the other tools here return a matrix. DSS must do the 
                    # same. --> otherwise error in rbind of line 3192
                    classes <- asClassVector(sampleList)
                    theDesign <- data.frame(condition=classes,
                        row.names=colnames(normGenesExpr)) 
                    cds <- newCountDataSet(as.matrix(round(
                        assayData(normGenesExpr)$exprs)),theDesign$condition)
                    #DESeq::sizeFactors(cds) <- 
                    #    normalizationFactor(normGenesExpr)
                    sizeFactors(cds) <- normalizationFactor(normGenesExpr)
                    #normGenesExpr <- as.matrix(round(DESeq::counts(cds,
                    #    normalized=TRUE)))
                    normGenesExpr <- as.matrix(round(counts(cds,
                        normalized=TRUE)))
                }
            )
            geneCountsExpr <- geneCounts[rownames(normGenesExpr),]
            geneDataExpr <- geneData[-theDeadInd]
            attr(geneDataExpr,"geneLength") <-
                attr(geneData,"geneLength")[-theDeadInd]
            
        }
        else {
            normGenesExpr <- normGenes
            geneCountsExpr <- geneCounts
            geneDataExpr <- geneData
            geneCountsDead <- geneDataDead <- geneCountsUnnorm <- NULL
        }
    }
    
    # Store the final filtered, maybe we do some stats
    geneDataFiltered <- c(geneDataZero,geneDataDead)
    if (!is.null(geneDataFiltered) && length(geneDataFiltered) > 0) {
        disp(length(geneDataFiltered)," genes filtered out")
        if (!is.null(geneDataZero) && length(geneDataZero) > 0)
            attr(geneDataFiltered,"geneLength") <- c(attr(geneDataZero,
                "geneLength"),attr(geneDataDead,"geneLength"))
        else
            attr(geneDataFiltered,"geneLength") <-
                attr(geneDataDead,"geneLength")
    }
    if (!is.null(geneFilters) || !is.null(exonFilters))
        disp(length(geneDataExpr)," genes remain after filtering")

    ############################################################################
    # END FILTERING SECTION
    ############################################################################

    # There is a small case that no genes are left after filtering...
    if(any(dim(normGenesExpr)==0))
        stopwrap("No genes left after gene and/or exon filtering! Try again ",
            "with no filtering or less strict filter rules...")

    if (!is.null(contrast) && !any(is.na(statistics))) {
        if (is.function(.progressFun)) {
            text <- paste("Statistical testing...")
            .progressFun(detail=text)
        }
        
        # Run the statistical test, normGenes is always a method-specific
        # object, handled in the metaseqr.stat.R stat.* functions
        cpList <- vector("list",length(contrast))
        names(cpList) <- contrast
        contrastList <- makeContrastList(contrast,sampleList)
        for (n in names(cpList)) {
            cpList[[n]] <- vector("list",length(statistics))
            names(cpList[[n]]) <- statistics
        }
        for (alg in statistics) {
            disp("Running statistical tests with: ",alg)    
            switch(alg,
                deseq = {
                    pList <- statDeseq(normGenesExpr,sampleList,contrastList,
                        statArgs[[alg]])
                    if (!is.na(pcut)) {
                        for (con in names(contrastList))
                            disp("  Contrast ",con,": found ",
                                length(which(pList[[con]]<=pcut))," genes")
                    }
                },
                deseq2 = {
                    pList <- statDeseq2(normGenesExpr,sampleList,contrastList,
                        statArgs[[alg]])
                    if (!is.na(pcut)) {
                        for (con in names(contrastList))
                            disp("  Contrast ",con,": found ",
                                length(which(pList[[con]]<=pcut))," genes")
                    }
                },   
                edger = {
                    pList <- statEdger(normGenesExpr,sampleList,contrastList,
                        statArgs[[alg]])
                    if (!is.na(pcut)) {
                        for (con in names(contrastList))
                            disp("  Contrast ",con,": found ",
                                length(which(pList[[con]]<=pcut))," genes")
                    }
                },
                noiseq = {
                    pList <- statNoiseq(normGenesExpr,sampleList,contrastList,
                        statArgs[[alg]],geneDataExpr,logOffset)
                    if (!is.na(pcut)) {
                        for (con in names(contrastList))
                            disp("  Contrast ",con,": found ",
                                length(which(pList[[con]]<=pcut))," genes")
                    }
                },
                bayseq = {
                    pList <- statBayseq(normGenesExpr,sampleList,contrastList,
                        statArgs[[alg]],libsizeList)
                    if (!is.na(pcut)) {
                        for (con in names(contrastList))
                            disp("  Contrast ",con,": found ",
                                length(which(pList[[con]]<=pcut))," genes")
                    }
                },
                limma = {
                    pList <- statLimma(normGenesExpr,sampleList,contrastList,
                        statArgs[[alg]])
                    if (!is.na(pcut)) {
                        for (con in names(contrastList))
                            disp("  Contrast ",con,": found ",
                                length(which(pList[[con]]<=pcut))," genes")
                    }
                },
                nbpseq = {
                    pList <- statNbpseq(normGenesExpr,sampleList,contrastList,
                        statArgs[[alg]],libsizeList)
                    if (!is.na(pcut)) {
                        for (con in names(contrastList))
                            disp("  Contrast ",con,": found ",
                                length(which(pList[[con]]<=pcut))," genes")
                    }
                },
                absseq = {
                    pList <- statAbsseq(normGenesExpr,sampleList,contrastList,
                        statArgs[[alg]])
                    if (!is.na(pcut)) {
                        for (con in names(contrastList))
                            disp("  Contrast ",con,": found ",
                                length(which(pList[[con]]<=pcut))," genes")
                    }
                },
                dss = {
                    pList <- statDss(normGenesExpr,sampleList,contrastList,
                        statArgs[[alg]])
                    # Order pList genes as in normGenesExpr, because dss outputs
                    # gene names in a different order
                    pList[[1]] <- pList[[1]][rownames(normGenesExpr)]
                    if (!is.na(pcut)) {
                        for (con in names(contrastList))
                            disp("  Contrast ",con,": found ",
                                length(which(pList[[con]]<=pcut))," genes")
                    }
                }
            )
            for (n in names(pList))
                cpList[[n]][[alg]] <- pList[[n]]
        }
        for (n in names(cpList))
            cpList[[n]] <- do.call("cbind",cpList[[n]])

        # Create the adjusted p-value matrices (if needed)
        if ("adj_p_value" %in% exportWhat) {
            adjCpList <- cmclapply(cpList,
                function(x,a) return(apply(x,2,p.adjust,a)),adjustMethod,
                rc=restrictCores)
            for (n in names(cpList)) {
                noi <- grep("noiseq",colnames(cpList[[n]]))
                if (length(noi)>0) {
                    # DESeq has not run in this case, FDR cannot be calculated
                    if (length(strsplit(n,"_vs_")[[1]])==2)
                        adjCpList[[n]][,noi] <- rep(NA,nrow(cpList[[n]]))
                }
            }
        }
        else
            adjCpList <- NULL
    }
    else
        # No contrast provided or no staistical tests selected, some dummy 
        # p-value data must exist for export
        cpList <- adjCpList <- NULL
    
    if (!is.null(contrast)) # In case of only statistics=NA
        contrastList <- makeContrastList(contrast,sampleList)

    # At this point, all method-specific objects must become matrices for  
    # exporting and plotting
    switch(class(normGenesExpr)[1],
        .CountDataSet = { # Has been processed with DESeq
            #normGenes <- round(DESeq::counts(normGenes,normalized=TRUE))
            normGenes <- round(counts(normGenes,normalized=TRUE))
            #normGenesExpr <- round(DESeq::counts(normGenesExpr,
            #    normalized=TRUE))
            normGenesExpr <- round(counts(normGenesExpr,normalized=TRUE))
        },
        DESeqDataSet = { # Has been processed with DESeq2
            normGenes <- round(DESeq2::counts(normGenes,normalized=TRUE))
            normGenesExpr <- round(DESeq2::counts(normGenesExpr,
                normalized=TRUE))
        },
        DGEList = { # Has been processed with edgeR
            # Trick found at http://cgrlucb.wikispaces.com/edgeR+spring2013
            sclR <- normGenes$samples$lib.size*normGenes$samples$norm.factors
            normGenes <- round(t(t(normGenes$counts)/sclR)*mean(sclR))
            sclN <- normGenesExpr$samples$lib.size *
                normGenesExpr$samples$norm.factors
            normGenesExpr <- round(t(t(normGenesExpr$counts)/sclN) *
                mean(sclN))
        },
        nbData = {
            normGenes <- as.matrix(round(sweep(normGenes$counts,2,
                normGenes$norm.factors,"*")))
            normGenesExpr <- as.matrix(round(sweep(normGenesExpr$counts,2,
                normGenes$norm.factors,"*")))
        },
        nbp = {
            normGenes <- as.matrix(round(normGenes$pseudo.counts))
            normGenesExpr <- as.matrix(round(normGenesExpr$pseudo.counts))
        },
        ABSDataSet = {
            normGenes <- as.matrix(round(excounts(normGenes)))
            normGenesExpr <- as.matrix(round(excounts(normGenesExpr)))
        },
        SeqCountSet = {
            # Way to take normalized counts out of DSS as a matrix
            classes <- asClassVector(sampleList)
            theDesign <- data.frame(condition=classes,
                row.names=colnames(normGenes)) 
            cds <- newCountDataSet(as.matrix(round(assayData(normGenes)$exprs)),
                theDesign$condition)
            #DESeq::sizeFactors(cds) <- normalizationFactor(normGenes)
            sizeFactors(cds) <- normalizationFactor(normGenes)
            #normGenes <- as.matrix(round(DESeq::counts(cds,normalized=TRUE)))
            normGenes <- as.matrix(round(counts(cds,normalized=TRUE)))
            cdsExpr <- newCountDataSet(as.matrix(round(assayData(
                normGenesExpr)$exprs)),theDesign$condition)
            #DESeq::sizeFactors(cdsExpr) <- normalizationFactor(normGenesExpr)
            sizeFactors(cdsExpr) <- normalizationFactor(normGenesExpr)
            #normGenesExpr <- as.matrix(round(DESeq::counts(cdsExpr,
            #    normalized=TRUE)))
            normGenesExpr <- as.matrix(round(counts(cdsExpr,
                normalized=TRUE)))
        }
        # We don't need the matrix case
    )

    # Now that everything is a matrix, export the normalized counts if asked
    if (exportCountsTable) {
        geneDataExprExp <- as.data.frame(geneDataExpr)
        geneDataExprExp <- geneDataExprExp[,c(1,2,3,6,7,5,8,9)]
        colnames(geneDataExprExp)[1] <- "chromosome"
        geneDataFilteredExp <- as.data.frame(geneDataFiltered)
        geneDataFilteredExp <- geneDataFilteredExp[,c(1,2,3,6,7,5,8,9)]
        colnames(geneDataFilteredExp)[1] <- "chromosome"
        disp("Exporting and compressing normalized read counts table to ",
            file.path(PROJECT_PATH[["lists"]],"normalized_counts_table.txt"))
        expo <- cbind(
            rbind(geneDataExprExp,geneDataFilteredExp),
            rbind(normGenesExpr,geneCountsZero,geneCountsDead)
        )
        resFile <- file.path(PROJECT_PATH[["lists"]],
            "normalized_counts_table.txt.gz")
        gzfh <- gzfile(resFile,"w")
        write.table(expo,gzfh,sep="\t",row.names=FALSE,quote=FALSE)
        close(gzfh)
    }

    # Calculate meta-statistics, if more than one statistical algorithm has been
    # used
    if (!is.null(contrast) && !any(is.na(statistics))) {
        if (length(statistics)>1) {
            sumpList <- metaTest(
                cpList=cpList,
                metaP=metaP,
                counts=normGenesExpr,
                sampleList=sampleList,
                statistics=statistics,
                statArgs=statArgs,
                libsizeList=libsizeList,
                nperm=nperm,
                weight=weight,
                pOffset=pOffset,
                rc=restrictCores
            )
        }
        # We assign the p-values from the only statistic used to sumpList in
        # order to use it for stat plots
        else
            sumpList <- cpList
        # Useless for one statistics but just for safety
        if ("adj_meta_p_value" %in% exportWhat) 
            adjSumpList <- cmclapply(sumpList,
                function(x,a) return(p.adjust(x,a)),adjustMethod,
                    rc=restrictCores)
        else
            adjSumpList <- NULL
    }
    else
        sumpList <- adjSumpList <- NULL

    ############################################################################
    #                            EXPORT SECTION
    ############################################################################

    if (is.function(.progressFun)) {
        text <- paste("Exporting...")
        .progressFun(detail=text)
    }

    # Bind all the flags
    if (countType=="gene")
        flags <- geneFilterFlags
    else if (countType=="utr")
        flags <- geneFilterFlags
    else if (countType=="exon") {
        if (!is.null(exonFilterFlags)) {
            flags <- cbind(geneFilterFlags,
                as.matrix(exonFilterFlags[rownames(geneFilterFlags),]))
            nams <- c(colnames(geneFilterFlags),colnames(exonFilterFlags))
            rownames(flags) <- rownames(geneFilterFlags)
            colnames(flags) <- nams
        }
        else
            flags <- geneFilterFlags
    }
    
    disp("Building output files...")
    if (outList) 
        out <- makeExportList(contrast)
    else 
        out <- NULL
    if (report) 
        html <- makeExportList(contrast) 
    else 
        html <- NULL
    if ("rpgm" %in% exportScale)
        fa <- attr(geneData,"geneLength")
    else
        fa <- NULL
    if ("normalized" %in% exportValues) {
        fac <- fa[rownames(normGenesExpr)]
        normList <- makeTransformation(normGenesExpr,exportScale,fac,logOffset)
    }
    else
        normList <- NULL
    if ("raw" %in% exportValues) {
        fac <- fa[rownames(geneCountsExpr)]
        rawList <- makeTransformation(geneCountsExpr,exportScale,fac,logOffset)
    }
    else
        rawList <- NULL
    if ("flags" %in% exportWhat)
        goodFlags <- flags[rownames(normGenesExpr),]
    else
        goodFlags <- NULL

    if (!is.null(geneCountsZero) || !is.null(geneCountsDead)) {
        geneCountsFiltered <- rbind(geneCountsZero,geneCountsDead)
        geneCountsUnnormFiltered <- rbind(geneCountsZero,
            geneCountsUnnorm)
        if ("normalized" %in% exportValues) {
            fac <- fa[rownames(geneCountsFiltered)]
            normListFiltered <- makeTransformation(geneCountsFiltered,
                exportScale,fac,logOffset)
        }
        else
            normListFiltered <- NULL
        if ("raw" %in% exportValues) {
            fac <- fa[rownames(geneCountsUnnormFiltered)]
            rawListFiltered <- makeTransformation(
                geneCountsUnnormFiltered,exportScale,fac,logOffset)
        }
        else
            rawListFiltered <- NULL
        if ("flags" %in% exportWhat && !is.null(flags))
            allFlags <- rbind(
                matrix(1,nrow(geneCountsZero),ncol(flags)),
                    flags[rownames(geneCountsDead),]
            )
        else
            allFlags <- NULL
    }
    else {
        geneCountsFiltered <- NULL
        geneCountsUnnormFiltered <- NULL
        allFlags <- NULL
    }
    
    # Export structure for SeqCVIBE
    if (.exportR2C) {
        actLen <- c(attr(geneDataExpr,"geneLength"),
            attr(geneDataFiltered,"geneLength"))
        names(actLen) <- c(names(geneDataExpr),names(geneDataFiltered))
        
        disp("Saving more count data to ",file.path(PROJECT_PATH[["data"]],
            "count_data.RData"))
        .createR2CExport(
            rbind(geneCountsExpr,geneCountsUnnormFiltered),
            rbind(normGenesExpr,geneCountsFiltered),
            c(geneDataExpr,geneDataFiltered),
            actLen,
            libsizeList,
            file.path(PROJECT_PATH[["data"]],"count_data.RData")
        )
    }
    
    if (!is.null(contrast)) {
        reportTables <- vector("list",length(contrast))
        names(reportTables) <- contrast
        
        for (cnt in contrast) {
            disp("  Contrast: ",cnt)
            disp("    Adding non-filtered data...")
            if (!any(is.na(statistics)))
                theExport <- buildExport(
                    geneData=geneDataExpr,
                    rawGeneCounts=geneCountsExpr,
                    normGeneCounts=normGenesExpr,
                    flags=goodFlags,
                    sampleList=sampleList,
                    cnt=cnt,
                    statistics=statistics,
                    rawList=rawList,
                    normList=normList,
                    pMat=cpList[[cnt]],
                    adjpMat=adjCpList[[cnt]],
                    sumP=sumpList[[cnt]],
                    adjSumP=adjSumpList[[cnt]],
                    exportWhat=exportWhat,
                    exportScale=exportScale,
                    exportValues=exportValues,
                    exportStats=exportStats,
                    logOffset=logOffset,
                    #report=report
                    report=FALSE
                )
            else
                theExport <- buildExport(
                    geneData=geneDataExpr,
                    rawGeneCounts=geneCountsExpr,
                    normGeneCounts=normGenesExpr,
                    flags=goodFlags,
                    sampleList=sampleList,
                    cnt=cnt,
                    rawList=rawList,
                    normList=normList,
                    exportWhat=exportWhat,
                    exportScale=exportScale,
                    exportValues=exportValues,
                    exportStats=exportStats,
                    logOffset=logOffset,
                    #report=report
                    report=FALSE
                )
            
            # Adjust the export based on what statistics have been done and a 
            # possible p-value cutoff
            export <- theExport$textTable
            colnames(export)[1] <- "chromosome"
            if (report)
                exportHtml <- theExport$htmlTable
            if (!any(is.na(statistics))) { # Ordering based on p-value
                if (!is.na(pcut)) {
                    if (length(statistics)>1) {
                        switch(metaP,
                            fisher = {
                                cutInd <- which(sumpList[[cnt]]<=pcut)
                            },
                            fperm = {
                                cutInd <- which(sumpList[[cnt]]<=pcut)
                            },
                            whitlock = {
                                cutInd <- which(sumpList[[cnt]]<=pcut)
                            },
                            dperm_min = {
                                cutInd <- which(sumpList[[cnt]]<=pcut)
                            },
                            dperm_max = {
                                cutInd <- which(sumpList[[cnt]]<=pcut)
                            },
                            dperm_weight = {
                                cutInd <- which(sumpList[[cnt]]<=pcut)
                            },
                            minp = {
                                cutInd <- which(sumpList[[cnt]]<=pcut)
                            },
                            maxp = {
                                cutInd <- which(sumpList[[cnt]]<=pcut)
                            },
                            weight = {
                                cutInd <- which(sumpList[[cnt]]<=pcut)
                            },
                            pandora = {
                                cutInd <- which(sumpList[[cnt]]<=pcut)
                            },
                            simes = {
                                cutInd <- which(sumpList[[cnt]]<=pcut)
                            },
                            none = {
                                cutInd <- which(sumpList[[cnt]]<=pcut)
                            }
                        )
                        pp <- sumpList[[cnt]][cutInd]
                        export <- export[cutInd,]
                        export <- export[order(pp),]
                        if (report) {
                            exportHtml <- exportHtml[cutInd,]
                            exportHtml <- exportHtml[order(pp),]
                        }
                    }
                    else {
                        cutInd <- which(sumpList[[cnt]]<=pcut)
                        pp <- sumpList[[cnt]][cutInd,]
                        export <- export[cutInd,]
                        export <- export[order(pp),]
                        if (report) {
                            exportHtml <- exportHtml[cutInd,]
                            exportHtml <- exportHtml[order(pp),]
                        }
                    }
                }
                else {
                    pp <- sumpList[[cnt]]
                    export <- export[order(pp),]
                    if (report)
                        exportHtml <- exportHtml[order(pp),]
                }
            }
            
            # Final safety trigger
            naInd <- grep("NA",rownames(export))
            if (length(naInd)>0) {
                export <- export[-naInd,]
                if (report) 
                    exportHtml <- exportHtml[-naInd,]
            }

            resFile <- file.path(PROJECT_PATH[["lists"]],
                paste("metaseqr_sig_out_",cnt,".txt.gz",sep=""))
            disp("    Writing output...")
            gzfh <- gzfile(resFile,"w")
            write.table(export,gzfh,quote=FALSE,row.names=FALSE,sep="\t")
            close(gzfh)
            if (outList)
                out[[cnt]] <- export

            if (!is.null(geneCountsZero) || !is.null(geneCountsDead)) {
                disp("    Adding filtered data...")
                theExportFiltered <- buildExport(
                    geneData=geneDataFiltered,
                    rawGeneCounts=geneCountsUnnormFiltered,
                    normGeneCounts=geneCountsFiltered,
                    flags=allFlags,
                    sampleList=sampleList,
                    cnt=cnt,
                    statistics=statistics,
                    rawList=rawListFiltered,
                    normList=normListFiltered,
                    exportWhat=exportWhat,
                    exportScale=exportScale,
                    exportValues=exportValues,
                    exportStats=exportStats,
                    logOffset=logOffset,
                    report=FALSE
                )

                # Now we should be having theExport and theExportFiltered. We do
                # not generate html output for filtered or total results just a
                # compressed text file. We thus have to append 
                # theExport$textTable and theExportFiltered$htmlTable before
                # writing the final output...
                exportAll <- rbind(theExport$textTable,
                    theExportFiltered$textTable)
                # ...and order them somehow... alphabetically according to row
                # names, as the annotation might not have been bundled...
                exportAll <- exportAll[order(rownames(exportAll)),]
                colnames(exportAll)[1] <- "chromosome"
                
                # Here, both filtered and unfiltered genes are passed to the 
                # output list.
                if (outList)
                    out[[cnt]] <- exportAll   
                
                resFile <- file.path(PROJECT_PATH[["lists"]],paste(
                    "metaseqr_all_out_",cnt,".txt.gz",sep=""))
                disp("    Writing output...")
                gzfh <- gzfile(resFile,"w")
                write.table(exportAll,gzfh,quote=FALSE,row.names=FALSE,sep="\t")
                close(gzfh)
            }
            
            # If report requested, build a more condensed summary table, while 
            # the complete tables are available for download
            if (report) {
                if (!any(is.na(statistics))) {
                    if (length(statistics) > 1) {
                        ew <- c("annotation","meta_p_value","adj_meta_p_value",
                            "fold_change","stats")
                        if (is.null(adjSumpList))
                            adjSumpList <- cmclapply(sumpList,
                                function(x,a) return(p.adjust(x,a)),
                                    adjustMethod,rc=restrictCores)
                    }
                    else
                        ew <- c("annotation","p_value","adj_p_value",
                            "fold_change","stats")
                }
                else
                    ew <- c("annotation","fold_change","stats")
                
                esc <- "rpgm"
                ev <- "normalized"
                est <- "mean"
                
                faR <- attr(geneDataExpr,"geneLength")          
                facR <- faR[rownames(normGenesExpr)]
                normListR <- makeTransformation(normGenesExpr,esc,facR,
                    logOffset)
                
                disp("    Adding report data...")
                if (!any(is.na(statistics))) {
                    reportTables[[cnt]] <- buildExport(
                        geneData=geneDataExpr,
                        rawGeneCounts=geneCountsExpr,
                        normGeneCounts=normGenesExpr,
                        flags=goodFlags,
                        sampleList=sampleList,
                        cnt=cnt,
                        statistics=statistics,
                        rawList=NULL,
                        normList=normListR,
                        pMat=cpList[[cnt]],
                        adjpMat=adjCpList[[cnt]],
                        sumP=sumpList[[cnt]],
                        adjSumP=adjSumpList[[cnt]],
                        exportWhat=ew,
                        exportScale=esc,
                        exportValues=ev,
                        exportStats=est,
                        logOffset=logOffset,
                        report=FALSE
                    )$textTable
                    reportTables[[cnt]] <- 
                        reportTables[[cnt]][names(pp)[order(pp)],,drop=FALSE]
                    
                    if (!is.null(reportTop)) {
                        plasm <- pcut
                        if (is.na(pcut))
                            plasm <- 0.05
                        
                        topi <- ceiling(reportTop*length(which(pp<=plasm)))
                        if (topi == 0)
                            topi <- 10
                        #topi <- ceiling(reportTop*nrow(reportTables[[cnt]]))
                        reportTables[[cnt]] <- 
                            reportTables[[cnt]][seq_len(topi),,drop=FALSE]
                    }
                }
                else {
                    reportTables[[cnt]] <- buildExport(
                        geneData=geneDataExpr,
                        rawGeneCounts=geneCountsExpr,
                        normGeneCounts=normGenesExpr,
                        flags=goodFlags,
                        sampleList=sampleList,
                        cnt=cnt,
                        rawList=NULL,
                        normList=normListR,
                        exportWhat=ew,
                        exportScale=esc,
                        exportValues=ev,
                        exportStats=est,
                        logOffset=logOffset,
                        report=FALSE
                    )$textTable
                    
                    if (!is.null(reportTop)) {
                        ii <- grep("fold_change_",colnames(reportTables[[cnt]]))
                        forOrder <- as.numeric(reportTables[[cnt]][,ii[1]])
                        oo <- sort(abs(forOrder),decreasing=TRUE,
                            index.return=TRUE)
                        topi <- ceiling(reportTop*length(oo$ix))
                        if (topi == 0)
                            topi <- 10  
                        reportTables[[cnt]] <- 
                            reportTables[[cnt]][oo$ix[seq_len(topi)],,
                                drop=FALSE]
                    }
                }
            }
        }
    }
    else {
        disp("  No contrast was specified, exporting only quantifications")
        disp("    Adding non-filtered data...")
        theExport <- buildExport(
            geneData=geneDataExpr,
            rawGeneCounts=geneCountsExpr,
            normGeneCounts=normGenesExpr,
            flags=goodFlags,
            sampleList=sampleList,
            statistics=statistics,
            rawList=rawList,
            normList=normList,
            exportWhat=exportWhat,
            exportScale=exportScale,
            exportValues=exportValues,
            exportStats=exportStats,
            logOffset=logOffset,
            report=FALSE
        )
        
        export <- theExport$textTable
        colnames(export)[1] <- "chromosome"
        if (report)
            exportHtml <- theExport$htmlTable
        
        naInd <- grep("NA",rownames(export))
        if (length(naInd)>0) {
            export <- export[-naInd,]
            if (report) 
                exportHtml <- exportHtml[-naInd,]
        }

        resFile <- file.path(PROJECT_PATH[["lists"]],"metaseqr_sig_out.txt.gz")
        disp("    Writing output...")
        gzfh <- gzfile(resFile,"w")
        write.table(export,gzfh,quote=FALSE,row.names=FALSE,sep="\t")
        close(gzfh)
        if (outList)
            out[[cnt]] <- export
            
        if (!is.null(geneCountsZero) || !is.null(geneCountsDead)) {
            disp("    Adding filtered data...")
            theExportFiltered <- buildExport(
                geneData=geneDataFiltered,
                rawGeneCounts=geneCountsUnnormFiltered,
                normGeneCounts=geneCountsFiltered,
                flags=allFlags,
                sampleList=sampleList,
                statistics=statistics,
                rawList=rawListFiltered,
                normList=normListFiltered,
                exportWhat=exportWhat,
                exportScale=exportScale,
                exportValues=exportValues,
                exportStats=exportStats,
                logOffset=logOffset,
                report=FALSE
            )

            # Now we should be having theExport and theExportFiltered. We do
            # not generate html output for filtered or total results just a
            # compressed text file. We thus have to append 
            # theExport$textTable and theExportFiltered$htmlTable before
            # writing the final output...
            exportAll <- rbind(theExport$textTable,
                theExportFiltered$textTable)
            # ...and order them somehow... alphabetically according to row
            # names, as the annotation might not have been bundled...
            exportAll <- exportAll[order(rownames(exportAll)),]
            colnames(exportAll)[1] <- "chromosome"
            
            # Here, both filtered and unfiltered genes are passed to the 
            # output list.
            if (outList)
                out[[cnt]] <- exportAll   
            
            resFile <- file.path(PROJECT_PATH[["lists"]],
                "metaseqr_all_out.txt.gz")
            disp("    Writing output...")
            gzfh <- gzfile(resFile,"w")
            write.table(exportAll,gzfh,quote=FALSE,row.names=FALSE,sep="\t")
            close(gzfh)
        }
        
        # If report requested, build a more condensed summary table, while 
        # the complete tables are available for download
        if (report) {
            ew <- c("annotation","stats")
            esc <- "rpgm"
            ev <- "normalized"
            est <- "mean"
            
            faR <- attr(geneDataExpr,"geneLength")          
            facR <- faR[rownames(normGenesExpr)]
            normListR <- makeTransformation(normGenesExpr,esc,facR,
                logOffset)
            
            disp("    Adding report data...")
            reportTables <- list(NT=buildExport(
                geneData=geneDataExpr,
                rawGeneCounts=geneCountsExpr,
                normGeneCounts=normGenesExpr,
                flags=goodFlags,
                sampleList=sampleList,
                statistics=statistics,
                rawList=NULL,
                normList=normListR,
                exportWhat=ew,
                exportScale=esc,
                exportValues=ev,
                exportStats=est,
                logOffset=logOffset,
                report=FALSE
            )$textTable)
            
            # Some kind of toping for the table must be done, most probably
            # based on top expressed genes
            if (!is.null(reportTop)) {
                ii <- grep("rpgm",colnames(reportTables[[1]]))
                forOrder <- as.matrix(reportTables[[1]][,ii])
                avgRpgm <- apply(forOrder,1,mean,na.rm=TRUE)
                oo <- sort(avgRpgm,decreasing=TRUE,index.return=TRUE)
                topi <- ceiling(reportTop*length(oo$ix))
                if (topi == 0)
                    topi <- 10  
                reportTables[[1]] <- 
                    reportTables[[1]][oo$ix[seq_len(topi)],,drop=FALSE]
            }
        }
    }

    ############################################################################
    # END EXPORT SECTION
    ############################################################################

    ############################################################################
    # BEGIN PLOTTING SECTION
    ############################################################################
    
    if (is.function(.progressFun)) {
        text <- paste("Plotting...")
        .progressFun(detail=text)
    }
    
    # Check if we have more than 6 samples in total, pairwise plots are not
    # meaningful
    if (length(unlist(sampleList)) > 6 && "pairwise" %in% qcPlots) {
        warnwrap("Pairwise sample comparison plot becomes indistinguishable ",
            "for more than 6 samples! Removing from plots...")
        qcPlots <- qcPlots[-which(qcPlots == "pairwise")]
    }
    
    if (!is.null(qcPlots)) {
        disp("Creating quality control graphs...")
        plots <- list(
            raw=c("mds","biodetection","countsbio","saturation","readnoise",
                "correl","pairwise"),
            norm=c("boxplot","gcbias","lengthbias","meandiff","meanvar",
                "rnacomp"),
            stat=c("deheatmap","volcano","mastat","biodist","deregulogram"),
            other=c("filtered"),
            venn=c("statvenn","foldvenn")
        )
        figRaw <- figUnorm <- figNorm <- figStat <- figOther <- figVenn <- 
            vector("list",length(figFormat))
        names(figRaw) <- names(figUnorm) <- names(figNorm) <-
            names(figStat) <- names(figOther) <- names(figVenn) <-
            figFormat
        if (is.null(contrast))
            contrastList <- NULL
        for (fig in figFormat) {
            disp("Plotting in ",fig," format...")
            figRaw[[fig]] <- metaseqrPlot(geneCounts,sampleList,
                annotation=geneData,plotType=intersect(qcPlots,plots$raw),
                isNorm=FALSE,output=fig,path=PROJECT_PATH$qc)
            
            figUnorm[[fig]] <- metaseqrPlot(geneCounts,sampleList,
                annotation=geneData,plotType=intersect(qcPlots,plots$norm),
                isNorm=FALSE,output=fig,path=PROJECT_PATH$normalization)
            
            # The annotation dimensions change...
            if (whenApplyFilter=="prenorm")
                figNorm[[fig]] <- metaseqrPlot(normGenes,sampleList,
                    annotation=geneDataExpr,plotType=intersect(qcPlots,
                    plots$norm),isNorm=TRUE,output=fig,
                    path=PROJECT_PATH$normalization) 
            else if (whenApplyFilter=="postnorm")
                figNorm[[fig]] <- metaseqrPlot(normGenes,sampleList,
                    annotation=geneData,plotType=intersect(qcPlots,
                    plots$norm),isNorm=TRUE,output=fig,
                    path=PROJECT_PATH$normalization)
            
            figStat[[fig]] <- metaseqrPlot(normGenesExpr,sampleList,
                annotation=geneDataExpr,contrastList=contrastList,
                pList=sumpList,thresholds=list(p=pcut,f=1),
                plotType=intersect(qcPlots,plots$stat),isNorm=TRUE,
                output=fig,path=PROJECT_PATH$statistics)

            if (!is.null(geneDataFiltered))
                figOther[[fig]] <- metaseqrPlot(geneDataFiltered,
                    sampleList,annotation=totalGeneData,
                    plotType=intersect(qcPlots,plots$other),isNorm=FALSE,
                    output=fig,path=PROJECT_PATH$qc)
            else 
                figOther[[fig]] <- NULL
            
            if ("statvenn" %in% qcPlots)
                figVenn[[fig]] <- metaseqrPlot(normGenesExpr,
                    sampleList,annotation=geneDataExpr,
                    contrastList=contrastList,pList=cpList,
                    thresholds=list(p=pcut,f=1),
                    plotType=intersect(qcPlots,plots$venn),
                    output=fig,path=PROJECT_PATH$statistics)
        }
        
        # Create also tracks if asked, all controls have been performed in the
        # beginning, so targets exist
        if (createTracks)
            tLink <- createSignalTracks(theList,org,stranded=trackInfo$stranded,
                normTo=trackInfo$normTo,urlBase=trackInfo$urlBase,
                exportPath=trackExportPath,hubInfo=trackInfo$hubInfo,
                fasta=trackInfo$fasta,gtf=trackInfo$gtf,
                overwrite=overwriteTracks,rc=restrictCores)
        else
            tLink <- NULL
        
        ########################################################################
        #assign("sampleList",sampleList,envir=parent.frame())
        #assign("geneCounts",geneCounts,envir=parent.frame())
        #assign("normGenes",normGenes,envir=parent.frame())
        #assign("normGenesExpr",normGenes,envir=parent.frame())
        #assign("sumpList",sumpList,envir=parent.frame())
        #assign("cpList",cpList,envir=parent.frame())
        #assign("contrastList",contrastList,envir=parent.frame())
        #assign("geneData",geneData,envir=parent.frame())
        #assign("geneDataExpr",geneDataExpr,envir=parent.frame())
        ########################################################################
    }

    ############################################################################
    # END PLOTTING SECTION
    ############################################################################
    
    ############################################################################
    # BEGIN REPORTING SECTION
    ############################################################################
    
    if (report) {
        obj <- list(
            sampleList=sampleList,
            contrastList=contrastList,
            qcPlots=qcPlots,
            geneCounts=geneCounts,
            geneData=geneData,
            geneDataExpr=geneDataExpr,
            geneDataFiltered=geneDataFiltered,
            totalGeneData=totalGeneData,
            normGenes=normGenes,
            normGenesExpr=normGenesExpr,
            cpList=cpList,
            sumpList=sumpList,
            pcut=pcut,
            metaP=metaP,
            whenApplyFilter=whenApplyFilter,
            PROJECT_PATH=PROJECT_PATH
        )
        if (reportDb == "sqlite")
            .createSqlPlotDb(obj)
        else if (reportDb == "dexie")
            .createDexiePlotDb(obj)
        
        disp("Creating HTML report...")
        
        if (!is.null(qcPlots)) {
            # First create zip archives of the figures
            disp("Compressing figures...")
            zipfiles <- file.path(PROJECT_PATH$plots,paste("metaseqr_figures_",
                figFormat,".zip",sep=""))
            names(zipfiles) <- figFormat
            for (f in figFormat) {
                files <- c(
                    dir(PROJECT_PATH$qc,pattern=paste(".",f,sep=""),
                        full.names=TRUE),
                    dir(PROJECT_PATH$normalization,pattern=paste(".",f,sep=""),
                        full.names=TRUE),
                    dir(PROJECT_PATH$statistics,pattern=paste(".",f,sep=""),
                        full.names=TRUE)
                )
                zip(zipfiles[f],files)
            }
            # Then create the final figure variables which brew will find...
            figRaw <- figRaw[["png"]]
            figUnorm <- figUnorm[["png"]]
            figNorm <- figNorm[["png"]]
            figStat <- figStat[["png"]]
            figOther <- figOther[["png"]]
            figVenn <- figVenn[["png"]]
        }
        else
            figRaw <- figUnorm <- figNorm <- figStat <- figOther <-
                figVenn <- NULL
        
        # Then see what is going of if default report changed
        if (tolower(reportTemplate)=="default") {
            if (exists("TEMPLATE")) {
                reportTemplate=list(
                    rmd=file.path(TEMPLATE,"metaseqr2_report.Rmd"),
                    loader=file.path(TEMPLATE,"dna_loader.gif")
                )
            }
            else
                reportTemplate=list(rmd=NULL,loader=NULL)
        }
        if (!is.null(reportTemplate$rmd)) {
            if (file.exists(reportTemplate$rmd)) {
                template <- reportTemplate$rmd
                hasTemplate <- TRUE
            }
            else {
                warnwrap(paste("The template file",reportTemplate$rmd,
                    "was not ","found! The HTML report will NOT be generated."))
                hasTemplate <- FALSE
            }
        }
        else {
            warnwrap(paste("The report option was enabled but no template ",
                "file is provided! The HTML report will NOT be generated."))
            hasTemplate <- FALSE
        }
        if (!is.null(reportTemplate$loader)) {
            if (file.exists(reportTemplate$loader))
                file.copy(from=reportTemplate$loader,to=PROJECT_PATH$media)
            else
                warnwrap(paste("The report loader image",reportTemplate$loader,
                    "was not found!"))
        }
        else
            warnwrap(paste("The report loader image was not provided!"))
        
        # Here we must download all required libraries and put them in the js
        # folder of the report to make it available offline
        if (offlineReport) {
            .downloadJsLibs(PROJECT_PATH,reportDb)
            paceHeader <- paste0("<script type=\"text/javascript\" ",
                "src=\"js/pace.min.js\"></script>")
        }
        else
            paceHeader <- paste0("<script type=\"text/javascript\" ",
                "src=\"https://raw.github.com/HubSpot/pace/v1.0.0/",
                "pace.min.js\"></script>")
        
        if (hasTemplate) {
            execTime <- elap2human(TB)
            REPORT_ENV <- .makeReportEnv(environment())
            
            file.copy(file.path(TEMPLATE,"metaseqr2_report.Rmd"),
                file.path(PROJECT_PATH$main,"metaseqr2_report.Rmd"),
                overwrite=TRUE)
            invisible(knitr::knit_meta(class=NULL,clean=TRUE))
            
            render(
                input=file.path(PROJECT_PATH$main,"metaseqr2_report.Rmd"),
                output_file="index.html",
                output_dir=PROJECT_PATH$main,
                envir=REPORT_ENV
            )
            gc(verbose=FALSE)
            
            # Remove the Rmd file after rendering the report
            unlink(file.path(PROJECT_PATH$main,"metaseqr2_report.Rmd"))
            
            ####################################################################
            # Replace a jQuery incompatibility bug line.. Hopefully to remove...
            # Also add pace.js in header on the top... header-includes does not
            # work...
            L <- readLines(file.path(PROJECT_PATH$main,"index.html"))
            # pace.js
            hi <- grep("<head>",L)
            if (length(hi) > 0)
                L[hi] <- paste0(L[hi],"\n",paceHeader)
            # jQuery bug
            ln <- grep(paste("$(\".menu\").find(\"li[data-target=\" +",
                "window.page + \"]\").trigger(\"click\");"),L,fixed=TRUE)
            if (length(ln) == 1)
                L[ln] <- paste("$(\".menu\").find(\"li[data-target='\" +",
                "window.page + \"']\").trigger(\"click\");")
            cat(L,file=file.path(PROJECT_PATH$main,"index.html"),sep="\n")
            ####################################################################
        }
    }

    ############################################################################
    # END REPORTING SECTION
    ############################################################################
    
    disp("\n",strftime(Sys.time()),": Data processing finished!\n")
    execTime <- elap2human(TB)
    disp("\n","Total processing time: ",execTime,"\n\n")

    if (outList) {
        tmp <- c(geneDataExpr,geneDataFiltered)
        a <- c(attr(geneDataExpr,"geneLength"),
            attr(geneDataFiltered,"geneLength"))
        names(a) <- rownames(tmp)
        attr(tmp,"geneLength") <- a
        if (!is.null(cpList)) {
            for (n in names(cpList)) {
                if (!is.null(geneDataFiltered)) {
                    filler <- matrix(NA,length(geneDataFiltered),
                        ncol(cpList[[n]]))
                    rownames(filler) <- names(geneDataFiltered)
                    colnames(filler) <- colnames(cpList[[n]])
                }
                else {
                    filler <- NULL
                    cpList[[n]] <- rbind(cpList[[n]],filler)
                    cpList[[n]] <- cpList[[n]][rownames(tmp),,drop=FALSE]
                }
            }
        }
        if (!is.null(adjCpList)) {
            for (n in names(adjCpList)) {
                if (!is.null(geneDataFiltered)) {
                    filler <- matrix(NA,length(geneDataFiltered),
                        ncol(adjCpList[[n]]))
                    rownames(filler) <- names(geneDataFiltered)
                    colnames(filler) <- colnames(cpList[[n]])
                }
                else
                    filler <- NULL
                adjCpList[[n]] <- rbind(adjCpList[[n]],filler)
                adjCpList[[n]] <- adjCpList[[n]][rownames(tmp),,drop=FALSE]
            }
        }
        if (!is.null(sumpList)) {
            for (n in names(sumpList)) {
                if (!is.null(geneDataFiltered)) {
                    filler <- rep(NA,length(geneDataFiltered))
                    names(filler) <- names(geneDataFiltered)
                }
                else
                    filler <- NULL
                if (is.matrix(sumpList[[n]])) {
                    # The following if-else was added because some runs had 
                    # filler=NULL while others do not. Sometimes this created a 
                    # problem and the simulations stopped. Now fixed.
                    if (is.null(filler)) {
                        sumpList[[n]] <- rbind(sumpList[[n]],filler)
                        sumpList[[n]] <- sumpList[[n]][rownames(tmp),,
                            drop=FALSE]
                    }
                    else {
                        filler=as.matrix(filler)
                        sumpList[[n]] <- rbind(sumpList[[n]],filler)
                        sumpList[[n]] <- sumpList[[n]][rownames(tmp),,
                            drop=FALSE]
                    }
                }
                else {
                    sumpList[[n]] <- c(sumpList[[n]],filler)
                    sumpList[[n]] <- sumpList[[n]][rownames(tmp)]
                }
            }
        }
        if (!is.null(adjSumpList)) {
            for (n in names(adjSumpList)) {
                if (!is.null(geneDataFiltered)) {
                    filler <- rep(NA,length(geneDataFiltered))
                    names(filler) <- names(geneDataFiltered)
                }
                else
                    filler <- NULL
                adjSumpList[[n]] <- c(adjSumpList[[n]],filler)
                adjSumpList[[n]] <- adjSumpList[[n]][rownames(tmp)]
            }
        }

        complete <- list(
            #call=as.list(match.call()),
            params=list(
                sampleList=sampleList,
                excludeList=excludeList,
                fileType=fileType,
                path=path,
                contrast=contrast,
                libsizeList=libsizeList,
                embedCols=embedCols,
                annotation=annotation,
                org=org,
                refdb=refdb,
                countType=countType,
                exonFilters=exonFilters,
                geneFilters=geneFilters,
                whenApplyFilter=whenApplyFilter,
                normalization=normalization,
                normArgs=normArgs,
                statistics=statistics,
                statArgs=statArgs,
                adjustMethod=adjustMethod,
                metaP=metaP,
                weight=weight,
                nperm=nperm,
                pcut=pcut,
                logOffset=logOffset,
                preset=preset,
                qcPlots=qcPlots,
                figFormat=figFormat,
                outList=outList,
                exportWhere=exportWhere,
                exportWhat=exportWhat,
                exportScale=exportScale,
                exportValues=exportValues,
                exportStats=exportStats,
                exportCountsTable=exportCountsTable,
                restrictCores=restrictCores,
                report=report,
                reportTop=reportTop,
                reportTemplate=reportTemplate,
                saveGeneModel=saveGeneModel,
                verbose=verbose,
                runLog=runLog,
                offlineReport=offlineReport,
                createTracks=createTracks,
                trackExportPath=trackExportPath,
                trackInfo=trackInfo
            ),
            filterCutoffs=list(
                exonFilter=list(
                    minActiveExons=NULL
                ),
                geneFilter=list(
                    length=geneFilters$length$length,
                    avgReads=if (is.null(geneFilterCutoff)) NULL else
                        round(geneFilterCutoff$avgReads,digits=5),
                    expression=list(
                        median=geneFilterCutoff$expression$median,
                        mean=geneFilterCutoff$expression$mean,
                        quantile=geneFilterCutoff$expression$quantile,
                        known=geneFilterCutoff$expression$known,
                        custom=geneFilterCutoff$expression$custom
                    ),
                    biotype=if (is.null(geneFilters$biotype)) NULL else
                        paste(names(geneFilters$biotype)[which(
                            unlist(geneFilters$biotype))],collapse=", ")
                ),
                zeroFiltered=length(theZeros),
                exonFiltered=length(unique(unlist(exonFilterResult))),
                geneFiltered=length(unique(unlist(geneFilterResult))),
                totalFiltered=length(theZeros)+length(theDead)
            ),
            geneData=tmp,
            rawCounts=rbind(geneCountsExpr,geneCountsUnnormFiltered),
            normCounts=rbind(normGenesExpr,geneCountsFiltered),
            flags=rbind(goodFlags,allFlags),
            sampleList=sampleList,
            contrastList=contrast,
            pValue=cpList,
            fdr=adjCpList,
            metaPValue=sumpList,
            metaFdr=adjSumpList
        )

        return(list(data=out,html=html,complete=complete))
    }
    
} # End metaseqr2


constructGeneModel <- function(countData,annoData,type,rc=NULL) {
    # countData is a matrix, must have exact rownames as annoData GRanges
    if (!all(rownames(countData) == names(annoData)))
        stop("The rownames of the provided counts are not the same (or in ",
            " the same order) as the provided annotation GRanges!")
    
    # Messaging...
    msg <- "provided count regions"
    if (!missing(type)) {
        if (type == "exon")
            msg <- "exons"
        else if (type == "utr")
            msg <- "transcripts (UTR regions)"
    }
    
    # Create splitting factor
    theGenes <- factor(annoData$gene_id,levels=unique(annoData$gene_id))
    
    # Split the counts vectors...
    theCounts <- cmclapply(colnames(countData),function(n,f,M) {
        disp("  Separating ",msg," per gene for ",n,"...")
        co <- M[,n]
        names(co) <- rownames(M)
        return(split(co,f))
    },theGenes,countData,rc=rc)
    names(theCounts) <- colnames(countData)
    
    # and the width of the merged exons
    w <- width(annoData)
    if (type == "exon")
        names(w) <- annoData$exon_id
    else if (type == "utr")
        names(w) <- annoData$transcript_id
    lengthList <- split(w,theGenes)
    attr(theCounts,"lengthList") <- lengthList
    # The exon lengths information is essentially redundant in the new version,
    # unless we need it for some QC distribution later on...
    
    return(theCounts)
}

.reduceGeneData <- function(exonData,geneData) {
    exonChrs <- unique(as.character(seqnames(exonData)))
    geneChrs <- unique(as.character(seqnames(geneData)))
    if (length(exonChrs) != length(geneChrs)) {
        m <- as.integer(match(seqnames(geneData),exonChrs))
        geneData <- geneData[which(!is.na(m))]
    }
    return(geneData)
}

.userOrg <- function(org,db=NULL) {
    ua <- getUserAnnotations(db)
    if (nrow(ua) == 0)
        return(FALSE)
    orgs <- unique(ua$organism)
    return(org %in% orgs)
}

.userRefdb <- function(refdb,db=NULL) {
    us <- getUserAnnotations(db)
    if (nrow(us) == 0)
        return(FALSE)
    refdbs <- unique(us$source)
    return(refdb %in% refdbs)
}

.createR2CExport <- function(raw,norm,gr,al,lib,output) {
    # Ensure the same order
    nameOrder <- names(gr)[order(names(gr))]
    
    # Reorder
    raw <- raw[nameOrder,]
    norm <- norm[nameOrder,]
    gr <- gr[nameOrder]
    al <- al[nameOrder]
    
    # Active length and annotation data frame
    attr(gr,"geneLength") <- al
    ann <- as.data.frame(gr)
    ann <- ann[,c(1,2,3,6,7,5,8,9)]
    colnames(ann)[1] <- "chromosome"
    
    # Create the list to be exported, naming violation with dot(.) in order
    # not to break current SeqCVIBE... Will correct in the future.
    b2c.out <- list(
        counts=raw,
        norm=norm,
        annotation=ann,
        length=al,
        libsize=lib
    )
    save(b2c.out,file=output,compress=TRUE)
}

.backwardsCompatibility <- function(dataFile) {
    the.counts <- count.type <- sample.list <- gene.data <- transcript.data <-
        exon.data <- NULL
    tmpEnv <- new.env()
    load(dataFile,tmpEnv)
    if (!is.null(tmpEnv$the.counts)) { # Old file
        # Copy to new
        tmpEnv$theCounts <- tmpEnv$the.counts
        tmpEnv$countsType <- tmpEnv$count.type
        tmpEnv$sampleList <- tmpEnv$sampleList
        tmpEnv$geneData <- tmpEnv$gene.data
        if (!is.null(tmpEnv$transcript.data))
            tmpEnv$transcriptData <- tmpEnv$transcript.data
        if (!is.null(tmpEnv$exon.data))
            tmpEnv$exonData <- tmpEnv$exon.data
        
        # Delete old
        if (exists("the.counts",envir=tmpEnv)) {
            rm(the.counts,count.type,sample.list,gene.data,envir=tmpEnv)
            if (!is.null(tmpEnv$transcript.data))
                rm(transcript.data,envir=tmpEnv)
            if (!is.null(tmpEnv$exon.data))
                rm(exon.data,envir=tmpEnv)
        }        
    }
    return(tmpEnv)
}

.excludeSamplesFromList <- function(L,s) {
    gl <- attr(L,"lengthList")
    L <- L[s]
    attr(L,"lengthList") <- gl
    return(L)
}

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metaseqR2 documentation built on Nov. 8, 2020, 7:34 p.m.