## ----knitrPrep, include=FALSE, eval = TRUE------------------------------------
knitr::opts_chunk$set(collapse = TRUE, comment = '#>', fig.width=5, fig.height=3)

## ----clear_memory, eval = TRUE------------------------------------------------
rm(list=ls()) 

## ----runchunks, eval = TRUE---------------------------------------------------
# Set whether or not the following chunks will be executed (run):
execute.vignette <- FALSE

## ----load_packages, eval = execute.vignette-----------------------------------
#  library(scales)
#  library(ggplot2)
#  library(data.table)
#  library(httk)
#  library(RColorBrewer)
#  library(grid)
#  library(gplots)

## ----plot_funcs, eval = execute.vignette--------------------------------------
#  # Multiple plot function
#  #
#  # ggplot objects can be passed in ..., or to plotlist (as a list of ggplot objects)
#  # - cols:   Number of columns in layout
#  # - layout: A matrix specifying the layout. If present, 'cols' is ignored.
#  #
#  # If the layout is something like matrix(c(1,2,3,3), nrow=2, byrow=TRUE),
#  # then plot 1 will go in the upper left, 2 will go in the upper right, and
#  # 3 will go all the way across the bottom.
#  #
#  multiplot <- function(..., plotlist=NULL, file, cols=1, layout=NULL, widths=unit(rep_len(1, cols), "null")) {
#  
#    # Make a list from the ... arguments and plotlist
#    plots <- c(list(...), plotlist)
#  
#    numPlots = length(plots)
#  
#    # If layout is NULL, then use 'cols' to determine layout
#    if (is.null(layout)) {
#      # Make the panel
#      # ncol: Number of columns of plots
#      # nrow: Number of rows needed, calculated from # of cols
#      layout <- matrix(seq(1, cols * ceiling(numPlots/cols)),
#                      ncol = cols, nrow = ceiling(numPlots/cols))
#    }
#  
#   if (numPlots==1) {
#      print(plots[[1]])
#  
#    } else {
#      # Set up the page
#      grid.newpage()
#      pushViewport(viewport(layout = grid.layout(nrow(layout), ncol(layout),widths=widths)))
#  
#      # Make each plot, in the correct location
#      for (i in 1:numPlots) {
#        # Get the i,j matrix positions of the regions that contain this subplot
#        matchidx <- as.data.frame(which(layout == i, arr.ind = TRUE))
#  
#        print(plots[[i]], vp = viewport(layout.pos.row = matchidx$row,
#                                        layout.pos.col = matchidx$col))
#      }
#    }
#  }
#  
#  scientific_10 <- function(x) {
#    out <- gsub("1e", "10^", scientific_format()(x))
#    out <- gsub("\\+","",out)
#    out <- gsub("10\\^01","10",out)
#    out <- parse(text=gsub("10\\^00","1",out))
#  }
#  
#  
#  lm_R2 <- function(m,prefix=NULL){
#      out <- substitute("MSE = "~mse*","~~italic(R)^2~"="~r2,
#           list(mse = signif(mean(m$residuals^2),3),
#                r2 = format(summary(m)$adj.r.squared, digits = 2)))
#      paste(prefix,as.character(as.expression(out)))
#  }
#  
#  heatmap.3 <- function(x,
#                        Rowv = TRUE, Colv = if (symm) "Rowv" else TRUE,
#                        distfun = dist,
#                        hclustfun = hclust,
#                        dendrogram = c("both","row", "column", "none"),
#                        symm = FALSE,
#                        scale = c("none","row", "column"),
#                        na.rm = TRUE,
#                        revC = identical(Colv,"Rowv"),
#                        add.expr,
#                        breaks,
#                        symbreaks = max(x < 0, na.rm = TRUE) || scale != "none",
#                        col = "heat.colors",
#                        colsep,
#                        rowsep,
#                        sepcolor = "white",
#                        sepwidth = c(0.05, 0.05),
#                        cellnote,
#                        notecex = 1,
#                        notecol = "cyan",
#                        na.color = par("bg"),
#                        trace = c("none", "column","row", "both"),
#                        tracecol = "cyan",
#                        hline = median(breaks),
#                        vline = median(breaks),
#                        linecol = tracecol,
#                        margins = c(5,5),
#                        ColSideColors,
#                        RowSideColors,
#                        side.height.fraction=0.3,
#                        cexRow = 0.2 + 1/log10(nr),
#                        cexCol = 0.2 + 1/log10(nc),
#                        labRow = NULL,
#                        labCol = NULL,
#                        key = TRUE,
#                        keysize = 1.5,
#                        density.info = c("none", "histogram", "density"),
#                        denscol = tracecol,
#                        symkey = max(x < 0, na.rm = TRUE) || symbreaks,
#                        densadj = 0.25,
#                        main = NULL,
#                        xlab = NULL,
#                        ylab = NULL,
#                        lmat = NULL,
#                        lhei = NULL,
#                        lwid = NULL,
#                        ColSideColorsSize = 1,
#                        RowSideColorsSize = 1,
#                        KeyValueName="Value",...){
#  
#      invalid <- function (x) {
#        if (missing(x) || is.null(x) || length(x) == 0)
#            return(TRUE)
#        if (is.list(x))
#            return(all(sapply(x, invalid)))
#        else if (is.vector(x))
#            return(all(is.na(x)))
#        else return(FALSE)
#      }
#  
#      x <- as.matrix(x)
#      scale01 <- function(x, low = min(x), high = max(x)) {
#          x <- (x - low)/(high - low)
#          x
#      }
#      retval <- list()
#      scale <- if (symm && missing(scale))
#          "none"
#      else match.arg(scale)
#      dendrogram <- match.arg(dendrogram)
#      trace <- match.arg(trace)
#      density.info <- match.arg(density.info)
#      if (length(col) == 1 && is.character(col))
#          col <- get(col, mode = "function")
#      if (!missing(breaks) && (scale != "none"))
#          warning("Using scale=\"row\" or scale=\"column\" when breaks are",
#              "specified can produce unpredictable results.", "Please consider using only one or the other.")
#      if (is.null(Rowv) || is.na(Rowv))
#          Rowv <- FALSE
#      if (is.null(Colv) || is.na(Colv))
#          Colv <- FALSE
#      else if (Colv == "Rowv" && !isTRUE(Rowv))
#          Colv <- FALSE
#      if (length(di <- dim(x)) != 2 || !is.numeric(x))
#          stop("`x' must be a numeric matrix")
#      nr <- di[1]
#      nc <- di[2]
#      if (nr <= 1 || nc <= 1)
#          stop("`x' must have at least 2 rows and 2 columns")
#      if (!is.numeric(margins) || length(margins) != 2)
#          stop("`margins' must be a numeric vector of length 2")
#      if (missing(cellnote))
#          cellnote <- matrix("", ncol = ncol(x), nrow = nrow(x))
#      if (!inherits(Rowv, "dendrogram")) {
#          if (((!isTRUE(Rowv)) || (is.null(Rowv))) && (dendrogram %in%
#              c("both", "row"))) {
#              if (is.logical(Colv) && (Colv))
#                  dendrogram <- "column"
#              else dedrogram <- "none"
#              warning("Discrepancy: Rowv is FALSE, while dendrogram is `",
#                  dendrogram, "'. Omitting row dendogram.")
#          }
#      }
#      if (!inherits(Colv, "dendrogram")) {
#          if (((!isTRUE(Colv)) || (is.null(Colv))) && (dendrogram %in%
#              c("both", "column"))) {
#              if (is.logical(Rowv) && (Rowv))
#                  dendrogram <- "row"
#              else dendrogram <- "none"
#              warning("Discrepancy: Colv is FALSE, while dendrogram is `",
#                  dendrogram, "'. Omitting column dendogram.")
#          }
#      }
#      if (inherits(Rowv, "dendrogram")) {
#          ddr <- Rowv
#          rowInd <- order.dendrogram(ddr)
#      }
#      else if (is.integer(Rowv)) {
#          hcr <- hclustfun(distfun(x))
#          ddr <- as.dendrogram(hcr)
#          ddr <- reorder(ddr, Rowv)
#          rowInd <- order.dendrogram(ddr)
#          if (nr != length(rowInd))
#              stop("row dendrogram ordering gave index of wrong length")
#      }
#      else if (isTRUE(Rowv)) {
#          Rowv <- rowMeans(x, na.rm = na.rm)
#          hcr <- hclustfun(distfun(x))
#          ddr <- as.dendrogram(hcr)
#          ddr <- reorder(ddr, Rowv)
#          rowInd <- order.dendrogram(ddr)
#          if (nr != length(rowInd))
#              stop("row dendrogram ordering gave index of wrong length")
#      }
#      else {
#          rowInd <- nr:1
#      }
#      if (inherits(Colv, "dendrogram")) {
#          ddc <- Colv
#          colInd <- order.dendrogram(ddc)
#      }
#      else if (identical(Colv, "Rowv")) {
#          if (nr != nc)
#              stop("Colv = \"Rowv\" but nrow(x) != ncol(x)")
#          if (exists("ddr")) {
#              ddc <- ddr
#              colInd <- order.dendrogram(ddc)
#          }
#          else colInd <- rowInd
#      }
#      else if (is.integer(Colv)) {
#          hcc <- hclustfun(distfun(if (symm)
#              x
#          else t(x)))
#          ddc <- as.dendrogram(hcc)
#          ddc <- reorder(ddc, Colv)
#          colInd <- order.dendrogram(ddc)
#          if (nc != length(colInd))
#              stop("column dendrogram ordering gave index of wrong length")
#      }
#      else if (isTRUE(Colv)) {
#          Colv <- colMeans(x, na.rm = na.rm)
#          hcc <- hclustfun(distfun(if (symm)
#              x
#          else t(x)))
#          ddc <- as.dendrogram(hcc)
#          ddc <- reorder(ddc, Colv)
#          colInd <- order.dendrogram(ddc)
#          if (nc != length(colInd))
#              stop("column dendrogram ordering gave index of wrong length")
#      }
#      else {
#          colInd <- 1:nc
#      }
#      retval$rowInd <- rowInd
#      retval$colInd <- colInd
#      retval$call <- match.call()
#      x <- x[rowInd, colInd]
#      x.unscaled <- x
#      cellnote <- cellnote[rowInd, colInd]
#      if (is.null(labRow))
#          labRow <- if (is.null(rownames(x)))
#              (1:nr)[rowInd]
#          else rownames(x)
#      else labRow <- labRow[rowInd]
#      if (is.null(labCol))
#          labCol <- if (is.null(colnames(x)))
#              (1:nc)[colInd]
#          else colnames(x)
#      else labCol <- labCol[colInd]
#      if (scale == "row") {
#          retval$rowMeans <- rm <- rowMeans(x, na.rm = na.rm)
#          x <- sweep(x, 1, rm)
#          retval$rowSDs <- sx <- apply(x, 1, sd, na.rm = na.rm)
#          x <- sweep(x, 1, sx, "/")
#      }
#      else if (scale == "column") {
#          retval$colMeans <- rm <- colMeans(x, na.rm = na.rm)
#          x <- sweep(x, 2, rm)
#          retval$colSDs <- sx <- apply(x, 2, sd, na.rm = na.rm)
#          x <- sweep(x, 2, sx, "/")
#      }
#      if (missing(breaks) || is.null(breaks) || length(breaks) < 1) {
#          if (missing(col) || is.function(col))
#              breaks <- 16
#          else breaks <- length(col) + 1
#      }
#      if (length(breaks) == 1) {
#          if (!symbreaks)
#              breaks <- seq(min(x, na.rm = na.rm), max(x, na.rm = na.rm),
#                  length = breaks)
#          else {
#              extreme <- max(abs(x), na.rm = TRUE)
#              breaks <- seq(-extreme, extreme, length = breaks)
#          }
#      }
#      nbr <- length(breaks)
#      ncol <- length(breaks) - 1
#      if (class(col) == "function")
#          col <- col(ncol)
#      min.breaks <- min(breaks)
#      max.breaks <- max(breaks)
#      x[x < min.breaks] <- min.breaks
#      x[x > max.breaks] <- max.breaks
#      if (missing(lhei) || is.null(lhei))
#          lhei <- c(keysize, 4)
#      if (missing(lwid) || is.null(lwid))
#          lwid <- c(keysize, 4)
#      if (missing(lmat) || is.null(lmat)) {
#          lmat <- rbind(4:3, 2:1)
#  
#          if (!missing(ColSideColors)) {
#             #if (!is.matrix(ColSideColors))
#             #stop("'ColSideColors' must be a matrix")
#              if (!is.character(ColSideColors) || nrow(ColSideColors) != nc)
#                  stop("'ColSideColors' must be a matrix of nrow(x) rows")
#              lmat <- rbind(lmat[1, ] + 1, c(NA, 1), lmat[2, ] + 1)
#              #lhei <- c(lhei[1], 0.2, lhei[2])
#               lhei=c(lhei[1], side.height.fraction*ColSideColorsSize/2, lhei[2])
#          }
#  
#          if (!missing(RowSideColors)) {
#              #if (!is.matrix(RowSideColors))
#              #stop("'RowSideColors' must be a matrix")
#              if (!is.character(RowSideColors) || ncol(RowSideColors) != nr)
#                  stop("'RowSideColors' must be a matrix of ncol(x) columns")
#              lmat <- cbind(lmat[, 1] + 1, c(rep(NA, nrow(lmat) - 1), 1), lmat[,2] + 1)
#              #lwid <- c(lwid[1], 0.2, lwid[2])
#              lwid <- c(lwid[1], side.height.fraction*RowSideColorsSize/2, lwid[2])
#          }
#          lmat[is.na(lmat)] <- 0
#      }
#  
#      if (length(lhei) != nrow(lmat))
#          stop("lhei must have length = nrow(lmat) = ", nrow(lmat))
#      if (length(lwid) != ncol(lmat))
#          stop("lwid must have length = ncol(lmat) =", ncol(lmat))
#      op <- par(no.readonly = TRUE)
#      on.exit(par(op))
#  
#      layout(lmat, widths = lwid, heights = lhei, respect = FALSE)
#  
#      if (!missing(RowSideColors)) {
#          if (!is.matrix(RowSideColors)){
#                  par(mar = c(margins[1], 0, 0, 0.5))
#                  image(rbind(1:nr), col = RowSideColors[rowInd], axes = FALSE)
#          } else {
#              par(mar = c(margins[1], 0, 0, 0.5))
#              rsc = t(RowSideColors[,rowInd, drop=FALSE])
#              rsc.colors = matrix()
#              rsc.names = names(table(rsc))
#              rsc.i = 1
#              for (rsc.name in rsc.names) {
#                  rsc.colors[rsc.i] = rsc.name
#                  rsc[rsc == rsc.name] = rsc.i
#                  rsc.i = rsc.i + 1
#              }
#              rsc = matrix(as.numeric(rsc), nrow = dim(rsc)[1])
#              image(t(rsc), col = as.vector(rsc.colors), axes = FALSE)
#              if (length(rownames(RowSideColors)) > 0) {
#                  axis(1, 0:(dim(rsc)[2] - 1)/max(1,(dim(rsc)[2] - 1)), rownames(RowSideColors), las = 2, tick = FALSE)
#              }
#          }
#      }
#  
#      if (!missing(ColSideColors)) {
#  
#          if (!is.matrix(ColSideColors)){
#              par(mar = c(0.5, 0, 0, margins[2]))
#              image(cbind(1:nc), col = ColSideColors[colInd], axes = FALSE)
#          } else {
#              par(mar = c(0.5, 0, 0, margins[2]))
#              csc = ColSideColors[colInd, , drop=FALSE]
#              csc.colors = matrix()
#              csc.names = names(table(csc))
#              csc.i = 1
#              for (csc.name in csc.names) {
#                  csc.colors[csc.i] = csc.name
#                  csc[csc == csc.name] = csc.i
#                  csc.i = csc.i + 1
#              }
#              csc = matrix(as.numeric(csc), nrow = dim(csc)[1])
#              image(csc, col = as.vector(csc.colors), axes = FALSE)
#              if (length(colnames(ColSideColors)) > 0) {
#                  axis(2, 0:(dim(csc)[2] - 1)/max(1,(dim(csc)[2] - 1)), colnames(ColSideColors), las = 2, tick = FALSE)
#              }
#          }
#      }
#  
#      par(mar = c(margins[1], 0, 0, margins[2]))
#      x <- t(x)
#      cellnote <- t(cellnote)
#      if (revC) {
#          iy <- nr:1
#          if (exists("ddr"))
#              ddr <- rev(ddr)
#          x <- x[, iy]
#          cellnote <- cellnote[, iy]
#      }
#      else iy <- 1:nr
#      image(1:nc, 1:nr, x, xlim = 0.5 + c(0, nc), ylim = 0.5 + c(0, nr), axes = FALSE, xlab = "", ylab = "", col = col, breaks = breaks, ...)
#      retval$carpet <- x
#      if (exists("ddr"))
#          retval$rowDendrogram <- ddr
#      if (exists("ddc"))
#          retval$colDendrogram <- ddc
#      retval$breaks <- breaks
#      retval$col <- col
#      if (!invalid(na.color) & any(is.na(x))) { # load library(gplots)
#          mmat <- ifelse(is.na(x), 1, NA)
#          image(1:nc, 1:nr, mmat, axes = FALSE, xlab = "", ylab = "",
#              col = na.color, add = TRUE)
#      }
#      axis(1, 1:nc, labels = labCol, las = 2, line = -0.5, tick = 0,
#          cex.axis = cexCol)
#      if (!is.null(xlab))
#          mtext(xlab, side = 1, line = margins[1] - 1.25)
#      axis(4, iy, labels = labRow, las = 2, line = -0.5, tick = 0,
#          cex.axis = cexRow)
#      if (!is.null(ylab))
#          mtext(ylab, side = 4, line = margins[2] - 1.25)
#      if (!missing(add.expr))
#          eval(substitute(add.expr))
#      if (!missing(colsep))
#          for (csep in colsep) rect(xleft = csep + 0.5, ybottom = rep(0, length(csep)), xright = csep + 0.5 + sepwidth[1], ytop = rep(ncol(x) + 1, csep), lty = 1, lwd = 1, col = sepcolor, border = sepcolor)
#      if (!missing(rowsep))
#          for (rsep in rowsep) rect(xleft = 0, ybottom = (ncol(x) + 1 - rsep) - 0.5, xright = nrow(x) + 1, ytop = (ncol(x) + 1 - rsep) - 0.5 - sepwidth[2], lty = 1, lwd = 1, col = sepcolor, border = sepcolor)
#      min.scale <- min(breaks)
#      max.scale <- max(breaks)
#      x.scaled <- scale01(t(x), min.scale, max.scale)
#      if (trace %in% c("both", "column")) {
#          retval$vline <- vline
#          vline.vals <- scale01(vline, min.scale, max.scale)
#          for (i in colInd) {
#              if (!is.null(vline)) {
#                  abline(v = i - 0.5 + vline.vals, col = linecol,
#                    lty = 2)
#              }
#              xv <- rep(i, nrow(x.scaled)) + x.scaled[, i] - 0.5
#              xv <- c(xv[1], xv)
#              yv <- 1:length(xv) - 0.5
#              lines(x = xv, y = yv, lwd = 1, col = tracecol, type = "s")
#          }
#      }
#      if (trace %in% c("both", "row")) {
#          retval$hline <- hline
#          hline.vals <- scale01(hline, min.scale, max.scale)
#          for (i in rowInd) {
#              if (!is.null(hline)) {
#                  abline(h = i + hline, col = linecol, lty = 2)
#              }
#              yv <- rep(i, ncol(x.scaled)) + x.scaled[i, ] - 0.5
#              yv <- rev(c(yv[1], yv))
#              xv <- length(yv):1 - 0.5
#              lines(x = xv, y = yv, lwd = 1, col = tracecol, type = "s")
#          }
#      }
#      if (!missing(cellnote))
#          text(x = c(row(cellnote)), y = c(col(cellnote)), labels = c(cellnote),
#              col = notecol, cex = notecex)
#      par(mar = c(margins[1], 0, 0, 0))
#      if (dendrogram %in% c("both", "row")) {
#          plot(ddr, horiz = TRUE, axes = FALSE, yaxs = "i", leaflab = "none")
#      }
#      else plot.new()
#      par(mar = c(0, 0, if (!is.null(main)) 5 else 0, margins[2]))
#      if (dendrogram %in% c("both", "column")) {
#          plot(ddc, axes = FALSE, xaxs = "i", leaflab = "none")
#      }
#      else plot.new()
#      if (!is.null(main))
#          title(main, cex.main = 1.5 * op[["cex.main"]])
#      if (key) {
#          par(mar = c(5, 4, 2, 1), cex = 0.75)
#          tmpbreaks <- breaks
#          if (symkey) {
#              max.raw <- max(abs(c(x, breaks)), na.rm = TRUE)
#              min.raw <- -max.raw
#              tmpbreaks[1] <- -max(abs(x), na.rm = TRUE)
#              tmpbreaks[length(tmpbreaks)] <- max(abs(x), na.rm = TRUE)
#          }
#          else {
#              min.raw <- min(x, na.rm = TRUE)
#              max.raw <- max(x, na.rm = TRUE)
#          }
#  
#          z <- seq(min.raw, max.raw, length = length(col))
#          image(z = matrix(z, ncol = 1), col = col, breaks = tmpbreaks,
#              xaxt = "n", yaxt = "n")
#          par(usr = c(0, 1, 0, 1))
#          lv <- pretty(breaks)
#          xv <- scale01(as.numeric(lv), min.raw, max.raw)
#          axis(1, at = xv, labels = lv)
#          if (scale == "row")
#              mtext(side = 1, "Row Z-Score", line = 2)
#          else if (scale == "column")
#              mtext(side = 1, "Column Z-Score", line = 2)
#          else mtext(side = 1, KeyValueName, line = 2)
#          if (density.info == "density") {
#              dens <- density(x, adjust = densadj, na.rm = TRUE)
#              omit <- dens$x < min(breaks) | dens$x > max(breaks)
#              dens$x <- dens$x[-omit]
#              dens$y <- dens$y[-omit]
#              dens$x <- scale01(dens$x, min.raw, max.raw)
#              lines(dens$x, dens$y/max(dens$y) * 0.95, col = denscol,
#                  lwd = 1)
#              axis(2, at = pretty(dens$y)/max(dens$y) * 0.95, pretty(dens$y))
#              title("Color Key\nand Density Plot")
#              par(cex = 0.5)
#              mtext(side = 2, "Density", line = 2)
#          }
#          else if (density.info == "histogram") {
#              h <- hist(x, plot = FALSE, breaks = breaks)
#              hx <- scale01(breaks, min.raw, max.raw)
#              hy <- c(h$counts, h$counts[length(h$counts)])
#              lines(hx, hy/max(hy) * 0.95, lwd = 1, type = "s",
#                  col = denscol)
#              axis(2, at = pretty(hy)/max(hy) * 0.95, pretty(hy))
#              title("Color Key\nand Histogram")
#              par(cex = 0.5)
#              mtext(side = 2, "Count", line = 2)
#          }
#          else title("Color Key")
#      }
#      else plot.new()
#      retval$colorTable <- data.frame(low = retval$breaks[-length(retval$breaks)],
#          high = retval$breaks[-1], color = retval$col)
#      invisible(retval)
#  }
#  
#  myclust <- function(c)
#  {
#    hclust(c,method="average")
#  }
#  
#  na.dist <- function(x,method="euclidian",...)
#  {
#    t.dist <- dist(x,...)
#    t.dist <- as.matrix(t.dist)
#    t.limit <- 1.1*max(t.dist,na.rm=TRUE)
#    t.dist[is.na(t.dist)] <- t.limit
#    t.dist <- as.dist(t.dist)
#    return(t.dist)
#  }

## ----fig3, eval = execute.vignette--------------------------------------------
#  physprop.matrix <- chem.invivo.PK.aggregate.data[,c("MW",
#                                      "logP",
#                                      "WaterSol",
#                                      "Neutral.pH74",
#                                      "Positive.pH74",
#                                      "Negative.pH74",
#                                      "Clint",
#                                      "Fup",
#                                      "Vdist",
#                                      "kelim",
#                                      "kgutabs",
#                                      "Fbio")]
#  rnames <- chem.invivo.PK.aggregate.data$Compound
#  rnames[rnames=="Bensulide"] <- c("Bensulide.Joint","Bensulide.NHEERL","Bensulide.RTI")
#  rnames[rnames=="Propyzamide"] <- c("Propyzamide.Joint","Propyzamide.NHEERL","Propyzamide.RTI")
#  rownames(physprop.matrix) <- rnames
#  
#  row.side.cols <- rep("Black",dim(physprop.matrix)[1])
#  row.side.cols[sapply(chem.invivo.PK.aggregate.data$CAS,is.pharma)] <- "Grey"
#  
#  apply(physprop.matrix,2,function(x) mean(x,na.rm=TRUE))
#  for (this.col in c(c(1,3,7,9:11),c(4:6,8,12))) physprop.matrix[,this.col] <- log10(10^-6+physprop.matrix[,this.col])
#  
#  physprop.matrix <- apply(physprop.matrix,2,function(x) (x-mean(x,na.rm=TRUE))/sd(x,na.rm=TRUE))

## ----PlotFigure3, eval = execute.vignette-------------------------------------
#  main_title="in vivo Toxicokinetic Parameters"
#  heatmap.2(physprop.matrix,
#            hclustfun=myclust,
#            Colv=FALSE,
#            distfun=na.dist,
#            na.rm = TRUE,
#            scale="none",
#            trace="none",
#            RowSideColors=row.side.cols,
#            col=brewer.pal(11,"Spectral"),
#            margins=c(8,10))
#  # The following has to be adjusted manually:
#  rect(0.65, 0.01, 0.87, 0.78, border="blue")
#  text(0.75,0.81,expression(paste("Estimated from ",italic("In Vivo")," Data")))

## ----Make FitData, eval = execute.vignette------------------------------------
#  # Use joint analysis data from both labs:
#  FitData <- subset(chem.invivo.PK.aggregate.data,Compound!="Bensulide"|Source=="Wambaugh et al. (2018), NHEERL/RTI")
#  FitData <- subset(FitData,Compound!="Propyzamide"|Source=="Wambaugh et al. (2018), NHEERL/RTI")
#  # Rename some columns to match original data files:
#  FitData$Compound.abbrev <- FitData$Abbrev
#  # Add a column indicating chemical type:
#  FitData$Chemical <- "Other"
#  FitData[sapply(FitData$CAS,is.pharma),"Chemical"] <- "Pharmaceutical"

## ----fig4, eval = execute.vignette--------------------------------------------
#  # Get rid of chemicals with Fup < LOD:
#  FitData.Fup <- subset(FitData,!(CAS%in%subset(chem.physical_and_invitro.data,Human.Funbound.plasma==0)$CAS))
#  
#  # Rename some columns to match original data files:
#  FitData.Fup$SelectedVdist <- FitData.Fup$Vdist
#  FitData.Fup$SelectedVdist.sd <- FitData.Fup$Vdist.sd
#  
#  #Predict volume of Distribution
#  FitData.Fup$Vdist.1comp.pred <- sapply(FitData.Fup$CAS,
#    function(x) suppressWarnings(calc_vdist(chem.cas=x,
#    species="Rat",
#    default.to.human = TRUE,
#    suppress.messages=TRUE)))
#  FitData.Fup$Vdist.1comp.pred.nocal <- sapply(FitData.Fup$CAS,
#    function(x) suppressWarnings(calc_vdist(chem.cas=x,
#    regression=FALSE,
#    species="Rat",
#    default.to.human = TRUE,
#    suppress.messages=TRUE)))
#  
#  FigVdista.fit <- lm(log(SelectedVdist)~log(Vdist.1comp.pred),data=subset(FitData.Fup,!is.na(SelectedVdist)&!is.na(Vdist.1comp.pred)))
#  summary(FigVdista.fit)
#  
#  FigVdista.fit.weighted <- lm(log(SelectedVdist)~log(Vdist.1comp.pred),data=subset(FitData.Fup,!is.na(SelectedVdist)&!is.na(Vdist.1comp.pred)),weights=1/SelectedVdist.sd^2)
#  summary(FigVdista.fit)
#  
#  FigVdista.fit.pharm <- lm(log(SelectedVdist)~log(Vdist.1comp.pred),data=subset(FitData.Fup,Chemical!="Other"&!is.na(Vdist.1comp.pred)))
#  summary(FigVdista.fit.pharm)
#  
#  FigVdista.fit.other <- lm(log(SelectedVdist)~log(Vdist.1comp.pred),data=subset(FitData.Fup,Chemical=="Other"&!is.na(Vdist.1comp.pred)))
#  summary(FigVdista.fit.other)
#  
#  dim(subset(FitData.Fup,!is.na(SelectedVdist.sd)&!is.na(Vdist.1comp.pred)))[1]
#  
#  FigVdista <- ggplot(data=subset(FitData.Fup,!is.na(Vdist.1comp.pred))) +
#      geom_segment(color="Grey",aes(x=Vdist.1comp.pred,y=exp(log(SelectedVdist)-SelectedVdist.sd),xend=Vdist.1comp.pred,yend=exp(log(SelectedVdist)+SelectedVdist.sd)))+
#      geom_text(aes_string(y="SelectedVdist",
#                           x="Vdist.1comp.pred",
#                           label="Compound.abbrev",
#                           color="Chemical"))+
#     scale_y_log10(label=scientific_10,limits = c(5*10^-2, 10^2)) +
#     scale_x_log10(label=scientific_10,limits = c(5*10^-2, 10^2)) +
#     annotation_logticks() +
#     geom_abline(slope=1, intercept=0) +
#     annotate("text", x = 1*10^-1, y = 3*10^1, label = "A",size=6)  +
#     ylab(expression(paste(italic("In vivo")," estimated Volume of Distribution (L/kg)"))) +
#     xlab(expression(paste("Calibrated ",italic("In vitro")," predicted ",V[d]," (L/kg)"))) +
#     theme_bw()  +
#     theme(legend.position="bottom")+
#      guides(shape=guide_legend(nrow=2,byrow=TRUE),color=guide_legend(nrow=2,byrow=TRUE))
#  
#  FigVdistb.fit <- lm(log(SelectedVdist)~log(Vdist.1comp.pred.nocal),data=subset(FitData.Fup,!is.na(Vdist.1comp.pred)))
#  summary(FigVdistb.fit)
#  
#  FigVdistb.fit.weighted <- lm(log(SelectedVdist)~log(Vdist.1comp.pred.nocal),data=subset(FitData.Fup,!is.na(Vdist.1comp.pred)),weights=1/SelectedVdist.sd^2)
#  summary(FigVdistb.fit)
#  
#  FigVdistb.fit.pharm <- lm(log(SelectedVdist)~log(Vdist.1comp.pred.nocal),data=subset(FitData.Fup,Chemical!="Other"&!is.na(Vdist.1comp.pred)))
#  summary(FigVdistb.fit.pharm)
#  
#  FigVdistb.fit.other<- lm(log(SelectedVdist)~log(Vdist.1comp.pred.nocal),data=subset(FitData.Fup,Chemical=="Other"&!is.na(Vdist.1comp.pred)))
#  summary(FigVdistb.fit.other)
#  
#  FigVdistb <- ggplot(data=subset(FitData.Fup,!is.na(Vdist.1comp.pred.nocal))) +
#     geom_segment(color="Grey",aes(x=Vdist.1comp.pred.nocal,y=exp(log(SelectedVdist)-SelectedVdist.sd),xend=Vdist.1comp.pred.nocal,yend=exp(log(SelectedVdist)+SelectedVdist.sd)))+
#     geom_text(aes_string(y="SelectedVdist",
#                           x="Vdist.1comp.pred.nocal",
#                           label="Compound.abbrev",
#                           color="Chemical"))+
#     scale_y_log10(label=scientific_10,limits = c(5*10^-2, 10^2)) +
#     scale_x_log10(label=scientific_10,limits = c(5*10^-2, 10^2)) +
#     annotation_logticks() +
#     geom_abline(slope=1, intercept=0) +
#     annotate("text", x = 1*10^-1, y = 3*10^1, label = "B",size=6) +
#     ylab(expression(paste(italic("In vivo")," estimated Volume of Distribution (L/kg)"))) +
#     xlab(expression(paste("Original ",italic("In vitro")," predicted ",V[d]," (L/kg)"))) +
#     theme_bw()  +
#     theme(legend.position="bottom")+
#      guides(shape=guide_legend(nrow=2,byrow=TRUE),color=guide_legend(nrow=2,byrow=TRUE))
#  
#  
#  
#  #dev.new(width=10,height=6)
#  multiplot(FigVdista,FigVdistb,cols=2,widths=c(1.75,1.75))
#  
#  
#  Fig4a.data <- subset(FitData.Fup,!is.na(SelectedVdist)&!is.na(Vdist.1comp.pred))
#  Fig4a.MSE <- mean((log(Fig4a.data$Vdist.1comp.pred)-log(Fig4a.data$SelectedVdist))^2)
#  
#  
#  Fig4b.data <- subset(FitData.Fup,!is.na(SelectedVdist)&!is.na(Vdist.1comp.pred.nocal))
#  Fig4b.MSE <- mean((log(Fig4b.data$Vdist.1comp.pred.nocal)-log(Fig4b.data$SelectedVdist))^2)
#  
#  

## ----fig5, eval = execute.vignette--------------------------------------------
#  #FitData.Fup$CLtot.1comp <- FitData.Fup$Vdist.1comp.meas*FitData.Fup$kelim.1comp.meas
#  #FitData.Fup$CLtot.1comp.sd <- (FitData.Fup$Vdist.1comp.meas.sd^2+FitData.Fup$kelim.1comp.meas.sd^2)^(1/2)
#  #FitData.Fup[is.na(CLtot.1comp.sd)]$CLtot.1comp.sd <- Inf
#  
#  #FitData.Fup[is.na(SelectedCLtot.sd)]$SelectedClearance.sd <- Inf
#  
#  FitData.Fup$SelectedCLtot <- FitData.Fup$Vdist*FitData.Fup$kelim
#  FitData.Fup$SelectedCLtot.sd <- (FitData.Fup$Vdist.sd^2 +
#    FitData.Fup$kelim.sd^2)^(1/2)
#  FitData.Fup$CLtot.1comp.pred <- sapply(FitData.Fup$CAS,
#    function(x) calc_total_clearance(chem.cas=x,
#    species="Rat",
#    default.to.human = TRUE,
#    suppress.messages=TRUE))
#  
#  Fig.SelectedClearance.fit <- lm(log(SelectedCLtot)~log(CLtot.1comp.pred),data=subset(FitData.Fup,!is.na(SelectedCLtot.sd)))
#  summary(Fig.SelectedClearance.fit)
#  Fig.SelectedClearance.fit.weighted <- lm(log(SelectedCLtot)~log(CLtot.1comp.pred),data=subset(FitData.Fup,!is.na(SelectedCLtot.sd)),weights=1/SelectedCLtot.sd^2)
#  summary(Fig.SelectedClearance.fit.weighted)
#  Fig.SelectedClearance.fit.pharma <- lm(log(SelectedCLtot)~log(CLtot.1comp.pred),data=subset(FitData.Fup,Chemical!="Other"&!is.na(SelectedCLtot.sd)),weights=1/SelectedCLtot.sd^2)
#  summary(Fig.SelectedClearance.fit.pharma)
#  Fig.SelectedClearance.fit.other<- lm(log(SelectedCLtot)~log(CLtot.1comp.pred),data=subset(FitData.Fup,Chemical=="Other"&!is.na(SelectedCLtot.sd)),weights=1/SelectedCLtot.sd^2)
#  summary(Fig.SelectedClearance.fit.other)
#  Fig.SelectedClearance.fit.pharma <- lm(log(SelectedCLtot)~log(CLtot.1comp.pred),data=subset(FitData.Fup,Chemical!="Other"))
#  summary(Fig.SelectedClearance.fit.pharma)
#  Fig.SelectedClearance.fit.other<- lm(log(SelectedCLtot)~log(CLtot.1comp.pred),data=subset(FitData.Fup,Chemical=="Other"))
#  summary(Fig.SelectedClearance.fit.other)
#  
#  Fig.SelectedClearance<- ggplot(data=FitData.Fup,aes(y=SelectedCLtot,x=CLtot.1comp.pred)) +
#      geom_segment(data=subset(FitData.Fup,is.finite(SelectedCLtot.sd)),color="grey",aes(x=CLtot.1comp.pred,y=exp(log(SelectedCLtot)-SelectedCLtot.sd),xend=CLtot.1comp.pred,yend=exp(log(SelectedCLtot)+SelectedCLtot.sd)))+
#    geom_text(aes_string(y="SelectedCLtot",
#                           x="CLtot.1comp.pred",
#                           label="Compound.abbrev",
#                           color="Chemical"))+
#  #    geom_point(data=twocomp.data,color="White",size=2,aes(shape=Source))+
#     scale_y_log10(label=scientific_10,limits = c(10^-4, 10^3)) +
#     scale_x_log10(label=scientific_10,limits = c(10^-4, 10^3)) +
#      annotation_logticks() +
#      geom_abline(slope=1, intercept=0) +
#       geom_line(aes(x = CLtot.1comp.pred, y = exp(Fig.SelectedClearance.fit.pharma$coefficients[1]+Fig.SelectedClearance.fit.pharma$coefficients[2]*log(CLtot.1comp.pred))), colour = "darkturquoise", linetype="dotted", size=1.5) +
#    geom_line(aes(x = CLtot.1comp.pred, y = exp(Fig.SelectedClearance.fit.other$coefficients[1]+Fig.SelectedClearance.fit.other$coefficients[2]*log(CLtot.1comp.pred))), colour = "red", linetype="dashed", size=1.5) +
#       ylab(expression(paste(italic("In vivo")," estimated clearance (mg/L/h)"))) +
#      xlab(expression(paste(italic("In vitro")," predicted clearance (mg/L/h)"))) +
#      theme_bw()   +
#      theme(legend.position="bottom")+
#      annotate("text",x = 10^2/3/3/3, y = 3*3*10^-4,size=4, label = lm_R2(Fig.SelectedClearance.fit.pharma,prefix="Pharmaceutical:"),parse=TRUE)+
#      annotate("text",x = 10^2/3/3/3, y = 3*3*3*10^-5,size=4, label = lm_R2(Fig.SelectedClearance.fit.other,prefix="Other:"),parse=TRUE)+
#      theme(plot.margin = unit(c(1,1,1,1), "cm"))+
#      guides(shape=guide_legend(nrow=2,byrow=TRUE),color=guide_legend(nrow=2,byrow=TRUE))
#  
#  
#  #dev.new(width=6,height=6)
#  print(Fig.SelectedClearance)
#  
#  paste("with",with(FitData.Fup,sum(SelectedCLtot<CLtot.1comp.pred,na.rm=TRUE)),"chemicals over-estimated and",with(FitData.Fup,sum(SelectedCLtot>CLtot.1comp.pred,na.rm=TRUE)),"under-estimated")
#  

## ----fig6, eval = execute.vignette--------------------------------------------
#  FitData$Selectedkgutabs <- FitData$kgutabs
#  # Cutoff from optimizer is 1000:
#  Figkgutabs <- ggplot(subset(FitData,Selectedkgutabs<999), aes(Selectedkgutabs, fill = Chemical)) +
#    geom_histogram(binwidth=0.5) +
#       scale_x_log10(label=scientific_10) +
#       ylab("Number of Chemicals")+
#       xlab("Absorption Rate from Gut (1/h)")+
#       theme_bw() +
#          theme(legend.position="bottom")
#  
#  #dev.new(width=6,height=6)
#  print(Figkgutabs)
#  
#  mean(subset(FitData,Selectedkgutabs<999)$Selectedkgutabs)
#  min(subset(FitData,Selectedkgutabs<999)$Selectedkgutabs)
#  max(subset(FitData,Selectedkgutabs<999)$Selectedkgutabs)
#  median(subset(FitData,Selectedkgutabs<999)$Selectedkgutabs)
#  

## ----fig7, eval = execute.vignette--------------------------------------------
#  FitData$SelectedFbio <- FitData$Fbio
#  
#  FigFbioa <- ggplot(data=FitData) +
#      geom_text(aes_string(y="SelectedFbio",
#                           x="Fbio.pred",
#                           label="Compound.abbrev",
#                           color="Chemical"))+
#     scale_y_log10(label=scientific_10,limits=c(10^-3,1)) +
#     scale_x_log10(label=scientific_10,limits=c(10^-3,1)) +
#  #    xlim(0, 1)+
#  #    ylim(0, 1)+
#      annotate("text", x = .015/10, y = 0.55, label = "A",size=6) +
#      annotation_logticks() +
#      geom_abline(slope=1, intercept=0) +
#      ylab(expression(paste(italic("In vivo")," estimated Fraction Bioavailable"))) +
#      xlab(expression(paste(italic("In silico")," predicted ",F[bio]))) +
#  #    scale_color_brewer(palette="Set2") +
#      theme_bw()  +
#      theme(legend.position="bottom")+
#      guides(shape=guide_legend(nrow=2,byrow=TRUE),color=guide_legend(nrow=2,byrow=TRUE))
#  
#  
#  FigFbiob <- ggplot(FitData, aes(SelectedFbio, fill = Chemical)) +
#    geom_histogram(binwidth=0.5) +
#      scale_x_log10(label=scientific_10,limits=c(10^-3,3)) +
#      annotate("text", x = .001, y = 18, label = "B",size=6) +
#      ylab("Number of Chemicals")+
#      xlab(expression(paste(italic("In vivo")," estimated Fraction Bioavailable"))) +
#      theme_bw()  +
#      theme(legend.position="bottom")+
#      guides(shape=guide_legend(nrow=2,byrow=TRUE),fill=guide_legend(nrow=2,byrow=TRUE))
#  
#  
#  
#  #dev.new(width=10,height=6)
#  multiplot(FigFbioa,FigFbiob,cols=2,widths=c(1.75,1.75))
#  
#  summary(lm(log(SelectedFbio)~log(Fbio.pred),data=FitData))
#  
#  paste("Fbio ranged from",signif(min(FitData[FitData$Chemical=="Pharmaceutical","SelectedFbio"],na.rm=TRUE),2),"to",signif(max(FitData[FitData$Chemical=="Pharmaceutical","SelectedFbio"],na.rm=TRUE),2),"for pharmaceutical compounds, but was observed to be as low as", signif(min(FitData[FitData$Chemical=="Other","SelectedFbio"],na.rm=TRUE),3),"for other compounds.")
#  
#  min(FitData$SelectedFbio,na.rm=TRUE)

## ----fig8, eval = execute.vignette--------------------------------------------
#  FitData$SelectedFbio <- FitData$Fbio
#  FitData$SelectedCss <- FitData$Css
#  FitData$SelectedCss.sd <- FitData$Css.sd
#  FitData$Css.1comp.pred <- sapply(FitData$CAS,
#    function(x) calc_analytic_css(chem.cas=x,
#    species="Rat",
#    model="3compartmentss",
#    suppress.messages=TRUE,
#    parameterize.args = list(
#      default.to.human=TRUE,
#      adjusted.Funbound.plasma=TRUE,
#      regression=TRUE,
#      minimum.Funbound.plasma=1e-4)))
#  
#  Fig.1compCss.fit <- lm(log(SelectedCss)~log(Css.1comp.pred),data=FitData,na.rm=TRUE)
#  Fig.1compCss.fit.weighted <- lm(log(SelectedCss)~log(Css.1comp.pred),data=FitData,na.rm=TRUE,weights=1/SelectedCss.sd^2)
#  Fig.1compCss.fit.pharma <- lm(log(SelectedCss)~log(Css.1comp.pred),data=subset(FitData,Chemical!="Other"),na.rm=TRUE)
#  Fig.1compCss.fit.other <- lm(log(SelectedCss)~log(Css.1comp.pred),data=subset(FitData,Chemical=="Other"),na.rm=TRUE)
#  
#  summary(Fig.1compCss.fit)
#  summary(Fig.1compCss.fit.pharma)
#  summary(Fig.1compCss.fit.other)
#  
#  
#  textx <- 10^-3
#  texty <- 1*10^1
#  
#  Fig.Cssa <- ggplot(data=FitData) +
#    geom_segment(color="grey",aes(x=Css.1comp.pred,y=exp(log(SelectedCss)-SelectedCss.sd),xend=Css.1comp.pred,yend=exp(log(SelectedCss)+SelectedCss.sd)))+
#    geom_text(size=4,aes_string(y="SelectedCss", x="Css.1comp.pred",label="Compound.abbrev",color="Chemical"))+
#    scale_y_log10(label=scientific_10,limits = c(5*10^-6, 110)) +
#    scale_x_log10(label=scientific_10,limits = c(5*10^-6, 110)) +
#    annotation_logticks() +
#    geom_abline(slope=1, intercept=0) +
#    ylab(expression(paste(italic("In vivo")," estimated ",C[ss]," (mg/L)"))) +
#   xlab(expression(paste(italic("In vitro")," predicted ",C[ss]," (mg/L)"))) +
#  #  scale_color_brewer(palette="Set2") +
#    theme_bw()  +
#    theme(legend.position="bottom")+
#      annotate("text", x = textx/15, y = 5*texty, label = "A",size=6) +
#    annotate("text",x = textx, y = texty,size=6, label = lm_R2(Fig.1compCss.fit),parse=TRUE)+
#      guides(shape=guide_legend(nrow=2,byrow=TRUE),color=guide_legend(nrow=2,byrow=TRUE))
#  #  annotate("text",x = textx/3, y = texty/3,size=4, label = lm_R2(Fig.1compCss.fit.weighted,prefix="Weighted:"),parse=TRUE)
#  #  annotate("text",x = textx, y = texty,size=4, label = lm_R2(Fig.1compCss.fit.pharma,prefix="Pharmaceutical:"),parse=TRUE)
#  #  annotate("text",x = textx, y = texty/3,size=4, label = lm_R2(Fig.1compCss.fit.other,prefix="Other:"),parse=TRUE)
#  
#  FitData$Css.Bio <- FitData$Css.1comp.pred*FitData$SelectedFbio
#  Fig.1compCssb.fit <- lm(log(SelectedCss)~log(Css.Bio),data=FitData,na.rm=TRUE)
#  Fig.1compCssb.fit.weighted <- lm(log(SelectedCss)~log(Css.Bio),data=FitData,na.rm=TRUE,weights=1/SelectedCss.sd^2)
#  Fig.1compCssb.fit.pharma <- lm(log(SelectedCss)~log(Css.Bio),data=subset(FitData,Chemical!="Other"),na.rm=TRUE)
#  Fig.1compCssb.fit.other <- lm(log(SelectedCss)~log(Css.Bio),data=subset(FitData,Chemical=="Other"),na.rm=TRUE)
#  
#  Fig.Cssb <- ggplot(data=FitData) +
#    geom_segment(color="grey",aes(x=Css.Bio,y=exp(log(SelectedCss)-SelectedCss.sd),xend=Css.Bio,yend=exp(log(SelectedCss)+SelectedCss.sd)))+
#    geom_text(size=4,aes_string(y="SelectedCss", x="Css.Bio",label="Compound.abbrev",color="Chemical"))+
#    scale_y_log10(label=scientific_10,limits = c(5*10^-6, 110)) +
#    scale_x_log10(label=scientific_10,limits = c(5*10^-6, 110)) +
#    annotation_logticks() +
#    geom_abline(slope=1, intercept=0) +
#    ylab(expression(paste(italic("In vivo")," estimated ",C[ss]," (mg/L)"))) +
#   xlab(expression(paste(italic("In vitro")," predicted ",C[ss]," (mg/L) Using Measured ", F[bio]))) +
#   # scale_color_brewer(palette="Set2") +
#    theme_bw()  +
#    theme(legend.position="bottom")+
#      annotate("text", x = textx/15, y = 5*texty, label = "B",size=6) +
#    annotate("text",x = textx, y = texty,size=6, label = lm_R2(Fig.1compCssb.fit),parse=TRUE)+
#      guides(shape=guide_legend(nrow=2,byrow=TRUE),color=guide_legend(nrow=2,byrow=TRUE))
#  
#  #dev.new(width=10,height=6)
#  multiplot(Fig.Cssa,Fig.Cssb,cols=2,widths=c(1.75,1.75))
#  
#  

## ----fig9, eval = execute.vignette--------------------------------------------
#  FitData$TriageCat <- FitData$Triage.Call
#  FitData$CssResidual <- log10(FitData$Css.1comp.pred/FitData$Css)
#  FitData[FitData$TriageCat%in%c("Does Not Reach Steady State","Plasma Binding Assay Failed"),"TriageCat"]<-"Problem"
#  FitData$TriageCat <- factor(FitData$TriageCat,levels=c(">10x Underestimated",">3.2x Underestimated","On the Order",">3.2x Overestimated",">10x Overestimated","Problem"))
#  
#  
#  Fig.Triage <- ggplot(data=subset(FitData,!is.na(TriageCat)&is.finite(CssResidual))) +
#    geom_text(size=4,aes_string(y="CssResidual", x="TriageCat",label="Compound.abbrev",color="Chemical"))+
#    geom_segment(aes(x = factor(">10x Underestimated",levels=levels(FitData$TriageCat)), y = log10(1/10), xend = factor(">10x Underestimated",levels=levels(FitData$TriageCat)), yend = log10(1/30)), size=3,colour = "grey") +
#   # geom_segment(aes(x = factor(">3.2x Underestimated",levels=levels(FitData$TriageCat)), y = log10(1/10), xend = factor(">3.2x Underestimated",levels=levels(FitData$TriageCat)), yend = log10(1/3.2)), size=3,colour = "grey") +
#    geom_segment(aes(x = factor("On the Order",levels=levels(FitData$TriageCat)), y = log10(1/3.2), xend = factor("On the Order",levels=levels(FitData$TriageCat)), yend = log10(3.2)), size=3,colour = "grey") +
#    geom_segment(aes(x = factor(">3.2x Overestimated",levels=levels(FitData$TriageCat)), y = log10(3.2), xend = factor(">3.2x Overestimated",levels=levels(FitData$TriageCat)), yend = log10(10)), size=3,colour = "grey") +
#    geom_segment(aes(x = factor(">10x Overestimated",levels=levels(FitData$TriageCat)), y = log10(10), xend = factor(">10x Overestimated",levels=levels(FitData$TriageCat)), yend = log10(500)), size=3,colour = "grey") +
#    geom_hline(yintercept=0)+
#    geom_hline(yintercept=log10(1/10),linetype="dashed")+
#      geom_hline(yintercept=log10(1/3.2),linetype="dashed")+
#    geom_hline(yintercept=log10(3.2),linetype="dashed")+
#    geom_hline(yintercept=log10(10),linetype="dashed")+
#    geom_text(size=4,aes_string(y="CssResidual", x="TriageCat",label="Compound.abbrev",color="Chemical"))+
#    scale_y_continuous(name=expression(paste("Actual error in ",C[ss]," prediction")),breaks=c(log10(1/10),log10(1/3.2),0,log10(3.2),1),labels=c(">10x Under",">3.2x Under","On the Order",">3.2x Over",">10x Over")) +
#    xlab("Predicted Error") +
#    theme_bw()  +
#    theme(legend.position="bottom")+
#    theme(axis.text.x = element_text(angle = 45, hjust = 1))+
#      guides(shape=guide_legend(nrow=2,byrow=TRUE),color=guide_legend(nrow=2,byrow=TRUE))
#  
#  
#  #dev.new(width=6,height=6)
#  print(Fig.Triage)
#  
#  
#  

## ----fig10, eval = execute.vignette-------------------------------------------
#  PKstats <- chem.invivo.PK.summary.data
#  # Add a column indicating chemical type:
#  PKstats$Chemical <- "Other"
#  PKstats[sapply(PKstats$CAS,is.pharma),"Chemical"] <- "Pharmaceutical"
#  
#  FigCmaxa.fit <- lm(log(Cmax)~log(Cmax.pred),data=subset(PKstats,is.finite(Cmax)))
#  summary(FigCmaxa.fit)
#  
#  FigCmaxa <- ggplot(data=subset(PKstats,is.finite(Cmax))) +
#      geom_point(size=3,aes_string(y="Cmax",
#                           x="Cmax.pred",
#                           shape="Route",
#                           color="Chemical"))+
#     scale_y_log10(label=scientific_10,limits = c(10^-4, 10^4)) +
#     scale_x_log10(label=scientific_10,limits = c(10^-4, 10^4)) +
#      annotation_logticks() +
#      geom_abline(slope=1, intercept=0) +
#      ylab(expression(paste(italic("In vivo")," estimated ",C[max]))) +
#      xlab(expression(paste(italic("In vitro")," predicted ",C[max]))) +
#  #    scale_color_brewer(palette="Set2") +
#      annotate("text", x = 10^-3, y = 300, label = "A",size=6) +
#      annotate("text",x = 3*10^1, y = 10^-3, label = lm_R2(FigCmaxa.fit),parse=TRUE,size=6) +
#      theme_bw()  +
#      theme(legend.position="bottom")+
#      guides(shape=guide_legend(nrow=2,byrow=TRUE),color=guide_legend(nrow=2,byrow=TRUE))
#  
#  
#  
#  
#  FigCmaxb.fit <- lm(log(Cmax)~log(Cmax.pred.Fbio),data=subset(PKstats,is.finite(Cmax)))
#  summary(FigCmaxb.fit)
#  
#  FigCmaxb <- ggplot(data=subset(PKstats,is.finite(Cmax))) +
#      geom_point(size=3,aes_string(y="Cmax",
#                           x="Cmax.pred.Fbio",
#                           shape="Route",
#                           color="Chemical"))+
#     scale_y_log10(label=scientific_10,limits = c(10^-4, 10^4)) +
#     scale_x_log10(label=scientific_10,limits = c(10^-4, 10^4)) +
#      annotation_logticks() +
#      geom_abline(slope=1, intercept=0) +
#      ylab(expression(paste(italic("In vivo")," estimated ",C[max]))) +
#      xlab(expression(paste("Predicted ", C[max], " Using Measured ", F[bio ]))) +
#      annotate("text", x = 10^-3, y = 300, label = "B",size=6) +
#      annotate("text",x = 3*10^1, y = 10^-3, label = lm_R2(FigCmaxb.fit),parse=TRUE,size=6) +
#  #    scale_color_brewer(palette="Set2") +
#      theme_bw()  +
#      theme(legend.position="bottom")+
#      guides(shape=guide_legend(nrow=2,byrow=TRUE),color=guide_legend(nrow=2,byrow=TRUE))
#  
#  #dev.new(width=10,height=6)
#  multiplot(FigCmaxa,FigCmaxb,cols=2,widths=c(1.75,1.75))
#  

## ----fig11, eval = execute.vignette-------------------------------------------
#  FigAUCa.fit <- lm(log(AUC)~log(AUC.pred),data=subset(PKstats,is.finite(log(AUC))))
#  FigAUCb.fit <- lm(log(AUC)~log(AUC.pred.Fbio),data=subset(PKstats,is.finite(log(AUC))))
#  summary(FigAUCa.fit)
#  summary(FigAUCb.fit)
#  
#  FigAUCa <- ggplot(data=subset(PKstats,is.finite(log(AUC)))) +
#      geom_point(size=3,aes_string(y="AUC",
#                           x="AUC.pred",
#                           shape="Route",
#                           color="Chemical"))+
#     scale_y_log10(label=scientific_10,limits = c(10^-3, 10^4)) +
#     scale_x_log10(label=scientific_10,limits = c(10^-3, 10^4)) +
#      annotation_logticks() +
#      geom_abline(slope=1, intercept=0) +
#      ylab(expression(paste(italic("In vivo")," estimated AUC (mg*h/L)"))) +
#      xlab(expression(paste(italic("In vitro")," predicted Area under the Curve (AUC, mg*h/L)"))) +
#      annotate("text", x = 10^-2, y = 3000, label = "A",size=6) +
#      annotate("text",x = 3*10^1, y = 10^-2, label = lm_R2(FigAUCa.fit),parse=TRUE,size=6) +
#      theme_bw()  +
#      theme(legend.position="bottom")+
#      guides(shape=guide_legend(nrow=2,byrow=TRUE),color=guide_legend(nrow=2,byrow=TRUE))
#  
#  
#  FigAUCb <- ggplot(data=subset(PKstats,is.finite(log(AUC)))) +
#      geom_point(size=3,aes_string(y="AUC",
#                           x="AUC.pred.Fbio",
#                           shape="Route",
#                           color="Chemical"))+
#     scale_y_log10(label=scientific_10,limits = c(10^-3, 10^4)) +
#     scale_x_log10(label=scientific_10,limits = c(10^-3, 10^4)) +
#      annotation_logticks() +
#      geom_abline(slope=1, intercept=0) +
#      ylab(expression(paste(italic("In vivo")," estimated AUC (mg*h/L)"))) +
#      xlab(expression(paste("Predicted AUC (mg*h/L) Using Measured ", F[bio]))) +
#      annotate("text", x = 10^-2, y = 3000, label = "B",size=6) +
#      annotate("text",x = 3*10^1, y = 10^-2, label = lm_R2(FigAUCb.fit),parse=TRUE,size=6) +
#      theme_bw()  +
#      theme(legend.position="bottom")+
#      guides(shape=guide_legend(nrow=2,byrow=TRUE),color=guide_legend(nrow=2,byrow=TRUE))
#  
#  #dev.new(width=10,height=6)
#  multiplot(FigAUCa,FigAUCb,cols=2,widths=c(1.75,1.75))
#  

