#' Get regions of LOH
#'
#' This function provides detailed LOH information by region.
#'
#'
#' @param res Return object of the \code{\link{runAbsoluteCN}} function.
#' @param id Candidate solution to extract LOH from. \code{id=1} will use the
#' maximum likelihood solution.
#' @param arm.cutoff Min fraction LOH on a chromosome arm to call whole arm
#' events.
#' @param keep.no.snp.segments Segments without heterozygous SNPs
#' have no LOH information. This defines whether these segments should
#' be reported anyways.
#' @return Returns \code{data.frame} with LOH regions.
#' @author Markus Riester
#' @seealso \code{\link{runAbsoluteCN}}
#' @examples
#'
#' data(purecn.example.output)
#' head(callLOH(purecn.example.output))
#'
#' @export callLOH
callLOH <- function(res, id = 1, arm.cutoff = 0.9,
                    keep.no.snp.segments = TRUE) {
    if (is.null(res$input$vcf)) {
        .stopUserError("runAbsoluteCN was run without a VCF file.")
    }
    chr.hash <- res$input$chr.hash
    centromeres <- .getCentromeres(res)
    armLocations <- .getArmLocations(res$input$vcf, chr.hash, centromeres)
    if (!nrow(armLocations)) {
        .stopUserError("Centromere positions not available or matching.")
    }
    armLocationsGR <- GRanges(armLocations)
    seg <- res$results[[id]]$seg

    bm <- res$results[[id]]$SNV.posterior$posteriors
    bm <- bm[which(!bm$ML.SOMATIC &
                    bm$GERMLINE.CONTLOW < 0.5 &
                    bm$GERMLINE.CONTHIGH < 0.5 &
                    bm$GERMLINE.HOMOZYGOUS < 0.5), ]

    if (is.null(bm)) {
        .stopRuntimeError("SNV.posterior NULL in callLOH.")
    }
    seg$seg.id <- seq(nrow(seg))
    seg$num.snps <- sapply(seg$seg.id, function(i)
            sum(bm$seg.id == i, na.rm = TRUE))
    seg$M <- bm$ML.M.SEGMENT[match(seg$seg.id, bm$seg.id)]
    seg$M.flagged <- bm$M.SEGMENT.FLAGGED[match(seg$seg.id, bm$seg.id)]
    seg$maf.expected <- sapply(seg$seg.id, function(i) {
            x <- bm$ML.AR[which(bm$seg.id == i)]
            if (!length(x)) return(NA)
            # they should all be the same, but make it more robust to artifacts
            # so use median
            median(sapply(x, function(y) ifelse(y > 0.5, 1 - y, y)))
            })
    seg$maf.observed <- sapply(seg$seg.id, function(i) {
            x <- bm$AR.ADJUSTED[which(bm$seg.id == i)]
            if (!length(x)) return(NA)
            median(sapply(x, function(y) ifelse(y > 0.5, 1 - y, y)))
            })

    if (!keep.no.snp.segments) {
        seg <- seg[!is.na(seg$M), ]
    }
    seg$chrom <- .add.chr.name(seg$chrom, chr.hash)

    # merge consecutive segments if they have same genotype
    i <- 1
    while (i < nrow(seg)) {
        key <- paste(seg$chrom, seg$C, seg$M)
        if (key[i] == key[i + 1]) {
            seg$loc.end[i] <- seg$loc.end[i + 1]
            seg$num.mark[i] <- seg$num.mark[i] + seg$num.mark[i + 1]
            seg <- seg[- (i + 1), ]
            next
        }
        i <- i + 1
    }

    segGR <- GRanges(seg)

    ov <- findOverlaps(armLocationsGR, segGR)
    segLOH <-  cbind(seg[subjectHits(ov), ], armLocations[queryHits(ov), ])
    segLOH$loc.start <- apply(segLOH[, c("loc.start", "start")], 1, max)
    segLOH$loc.end <- apply(segLOH[, c("loc.end", "end")], 1, min)
    segLOH$size <- segLOH$loc.end - segLOH$loc.start + 1
    segLOH$fraction.arm <- round(segLOH$size / armLocations$size[
        match(paste(segLOH$chrom, segLOH$arm),
        paste(armLocations$chrom, armLocations$arm))], digits = 2)
    segLOH$type <- ""
    segLOH$type[which(segLOH$C == 2 & segLOH$M == 0)] <- "COPY-NEUTRAL LOH"
    segLOH$type[which(segLOH$type == "" & segLOH$M == 0)] <- "LOH"
    idx <- segLOH$fraction.arm > arm.cutoff & segLOH$type != ""
    segLOH$type[idx] <- paste("WHOLE ARM",
        segLOH$type)[idx]
    segLOH$type[is.na(segLOH$M)] <- NA

    rownames(segLOH) <- NULL
    segLOH <- segLOH[, c("chrom", "loc.start", "loc.end", "arm", "C", "M",
        "type", "seg.mean", "num.mark", "num.snps", "M.flagged",
        "maf.expected", "maf.observed")]
    # standardize colnames
    colnames(segLOH)[1:3] <- c("chr", "start", "end")
    segLOH
}

.getCentromeres <- function(res) {
    # TODO remove this support for old data.frame centromeres in PureCN 1.12
    if (is(res$input$centromeres, "GRanges") ||
            is.null(res$input$centromeres)) {
        return(res$input$centromeres)
    }
    GRanges(res$input$centromeres)
}
    
.getArmLocations <- function(x, chr.hash, centromeres) {

    chromCoords <- suppressWarnings(t(vapply(split(
        start(x),
        as.character(seqnames(x))), function(y)
        c(min(y), max(y)), c(min = double(1), max = double(1)))))
    if (!is.null(centromeres)) {
        # split segments by centromere if available
        chromCoords <- chromCoords[as.integer(match(seqnames(centromeres), rownames(chromCoords))), ]
        rownames(chromCoords) <- NULL

        centromeres <- cbind(data.frame(centromeres), chromCoords)
        centromeres <- centromeres[complete.cases(centromeres), ]

        pArms <- centromeres[centromeres$min < centromeres$start,
            c("seqnames", "min", "start")]
        qArms <- centromeres[centromeres$max > centromeres$end,
            c("seqnames", "end", "max")]

        colnames(pArms) <- c("chrom", "start", "end")
        colnames(qArms) <- colnames(pArms)
        pArms$arm <- "p"
        if (nrow(qArms) == 0) {
          armLocations <- pArms
        } else {
          qArms$arm <- "q"
          armLocations <- rbind(pArms, qArms)
        }

    } else {
        armLocations <- data.frame(
                            chrom = rownames(chromCoords),
                            start = chromCoords[, 1],
                            end = chromCoords[, 2],
                            arm = "")
    }
    armLocations <- armLocations[order(match(armLocations$chrom,
        chr.hash[, 1])), ]
    armLocations$size <- armLocations$end - armLocations$start + 1
    armLocations
}
