suppressMessages({
  library("ggplot2")
  library("plotly")
  library("htmlwidgets")
  library("extrafont")
  library("grid")
  library("ggthemes")
})

# Constants for configuration
PLOT_WIDTH <- 12
PLOT_HEIGHT <- 8
BASE_SIZE <- 14

options(warn = 2, max.print = 100)

# Parse arguments
parse_arguments <- function() {
  if (interactive()) {
    args <- c(
      "Exp1",
      "/path/to/exp1_file.csv",
      "Exp2",
      "/path/to/exp2_file.csv",
      "/path/to/output_dir"
    )
  } else {
    args <- commandArgs(trailingOnly = TRUE)
  }
  list(
    exp1_name = args[1],
    exp1_file = normalizePath(args[2], mustWork = TRUE),
    exp2_name = args[3],
    exp2_file = normalizePath(args[4], mustWork = TRUE),
    output_dir = normalizePath(args[5], mustWork = FALSE)
  )
}

args <- parse_arguments()

# Create output directories if they don't exist
pairDirL <- file.path(args$output_dir, paste0("PairwiseCompareL_", args$exp1_name, "-", args$exp2_name))
pairDirK <- file.path(args$output_dir, paste0("PairwiseCompareK_", args$exp1_name, "-", args$exp2_name))
dir.create(pairDirL, showWarnings = FALSE, recursive = TRUE)
dir.create(pairDirK, showWarnings = FALSE, recursive = TRUE)

# Define themes and scales
theme_publication <- function(base_size = BASE_SIZE, base_family = "sans") {
  theme_foundation(base_size = base_size, base_family = base_family) +
    theme(
      plot.title = element_text(face = "bold", size = rel(1.2), hjust = 0.5),
      panel.background = element_rect(colour = NA),
      plot.background = element_rect(colour = NA),
      panel.border = element_rect(colour = NA),
      axis.title = element_text(face = "bold", size = rel(1)),
      axis.line = element_line(colour = "black"),
      panel.grid.major = element_line(colour = "#f0f0f0"),
      panel.grid.minor = element_blank(),
      legend.position = "bottom",
      legend.direction = "horizontal",
      legend.key.size = unit(0.2, "cm"),
      plot.margin = unit(c(10, 5, 5, 5), "mm"),
      strip.background = element_rect(colour = "#f0f0f0", fill = "#f0f0f0"),
      strip.text = element_text(face = "bold")
    )
}

theme_publication_legend_right <- function(base_size = BASE_SIZE, base_family = "sans") {
  theme_publication(base_size, base_family) +
    theme(
      legend.position = "right",
      legend.direction = "vertical",
      legend.key.size = unit(0.5, "cm")
    )
}

scale_fill_publication <- function(...) {
  discrete_scale("fill", "Publication", manual_pal(values = c(
    "#386cb0", "#fdb462", "#7fc97f", "#ef3b2c", "#662506",
    "#a6cee3", "#fb9a99", "#984ea3", "#ffff33"
  )), ...)
}

scale_colour_publication <- function(...) {
  discrete_scale("colour", "Publication", manual_pal(values = c(
    "#386cb0", "#fdb462", "#7fc97f", "#ef3b2c", "#662506",
    "#a6cee3", "#fb9a99", "#984ea3", "#ffff33"
  )), ...)
}

# Read and merge data
load_and_merge_data <- function(file1, file2) {
  df1 <- read.csv(file = file1, stringsAsFactors = FALSE, header = TRUE)
  df2 <- read.csv(file = file2, stringsAsFactors = FALSE, header = TRUE)
  merge(df1, df2, by = "Term_Avg", all = TRUE, suffixes = c("_df1", "_df2"))
}

# Generate a plot and save to PDF and HTML
generate_plot <- function(data, x_var, y_var, color_var, title, file_path, theme_function) {
  gg <- ggplot(data = data, aes_string(
    x = x_var,
    y = y_var,
    color = color_var
  )) +
    xlab(paste("GO Term Avg lm Z for", args$exp1_name)) +
    geom_rect(aes(xmin = -2, xmax = 2, ymin = -2, ymax = 2), color = "grey20", size = 0.25, alpha = 0.1, inherit.aes = FALSE, fill = NA) +
    geom_point(shape = 3) +
    ylab(paste("GO Term Avg lm Z for", args$exp2_name)) +
    ggtitle(title) +
    theme_function()

  pdf(file.path(file_path, ".pdf"), width = PLOT_WIDTH, height = PLOT_HEIGHT)
  print(gg)
  dev.off()

  pgg <- ggplotly(gg)
  htmlwidgets::saveWidget(pgg, file.path(file_path, ".html"))
}

# Identify and annotate specific interactions
annotate_interactions <- function(df, exp1_name, exp2_name, suffix) {
  df$Overlap_Avg <- NA
  interactions <- list(
    "df1_Specific_Aggravators" = which(df[[paste0("Z_lm_", suffix, "_Avg_df1")]] >= 2 & df[[paste0("Z_lm_", suffix, "_Avg_df2")]] < 2),
    "df1_Specific_Alleviators" = which(df[[paste0("Z_lm_", suffix, "_Avg_df1")]] <= -2 & df[[paste0("Z_lm_", suffix, "_Avg_df2")]] > -2),
    "df2_Specific_Aggravators" = which(df[[paste0("Z_lm_", suffix, "_Avg_df2")]] >= 2 & df[[paste0("Z_lm_", suffix, "_Avg_df1")]] < 2),
    "df2_Specific_Alleviators" = which(df[[paste0("Z_lm_", suffix, "_Avg_df2")]] <= -2 & df[[paste0("Z_lm_", suffix, "_Avg_df1")]] > -2),
    "Overlap_Aggravators" = which(df[[paste0("Z_lm_", suffix, "_Avg_df1")]] >= 2 & df[[paste0("Z_lm_", suffix, "_Avg_df2")]] >= 2),
    "Overlap_Alleviators" = which(df[[paste0("Z_lm_", suffix, "_Avg_df1")]] <= -2 & df[[paste0("Z_lm_", suffix, "_Avg_df2")]] <= -2),
    "df2_Aggravators_df1_Alleviators" = which(df[[paste0("Z_lm_", suffix, "_Avg_df2")]] >= 2 & df[[paste0("Z_lm_", suffix, "_Avg_df1")]] <= -2),
    "df2_Alleviators_df1_Aggravators" = which(df[[paste0("Z_lm_", suffix, "_Avg_df2")]] <= -2 & df[[paste0("Z_lm_", suffix, "_Avg_df1")]] >= 2)
  )
  annotation <- list(
    df1_Specific_Aggravators = paste(exp1_name, "Specific_Deletion_Enhancers", sep = "_"),
    df1_Specific_Alleviators = paste(exp1_name, "Specific_Deletion_Suppressors", sep = "_"),
    df2_Specific_Aggravators = paste(exp2_name, "Specific_Deletion_Enhancers", sep = "_"),
    df2_Specific_Alleviators = paste(exp2_name, "Specific_Deletion_Suppressors", sep = "_"),
    Overlap_Aggravators = "Overlapping_Deletion_Enhancers",
    Overlap_Alleviators = "Overlapping_Deletion_Suppressors",
    df2_Aggravators_df1_Alleviators = paste(exp2_name, "Deletion_Enhancers", exp1_name, "Deletion_Suppressors", sep = "_"),
    df2_Alleviators_df1_Aggravators = paste(exp2_name, "Deletion_Suppressors", exp1_name, "Deletion_Enhancers", sep = "_")
  )
  for (key in names(interactions)) {
    try(df$Overlap_Avg[interactions[[key]]] <- annotation[[key]])
  }
  df
}

# Rank and filter data
rank_and_filter_data <- function(df, suffix) {
  z1 <- df
  z1[[paste0("L_Subtract_SD_", suffix, "_df1")]] <- z1[[paste0("Z_lm_", suffix, "_Avg_df1")]] - z1[[paste0("Z_lm_", suffix, "_SD_df1")]]
  z1[[paste0("L_Subtract_SD_", suffix, "_df2")]] <- z1[[paste0("Z_lm_", suffix, "_Avg_df2")]] - z1[[paste0("Z_lm_", suffix, "_SD_df2")]]
  
  z2 <- df
  z2[[paste0("L_Subtract_SD_", suffix, "_df1")]] <- z2[[paste0("Z_lm_", suffix, "_Avg_df1")]] + z2[[paste0("Z_lm_", suffix, "_SD_df1")]]
  z2[[paste0("L_Subtract_SD_", suffix, "_df2")]] <- z2[[paste0("Z_lm_", suffix, "_Avg_df2")]] + z2[[paste0("Z_lm_", suffix, "_SD_df2")]]
  
  df_above_threshold <- df[!is.na(df$Overlap_Avg), ]
  df_above_threshold$df1_Rank <- rank(-df_above_threshold[[paste0("Z_lm_", suffix, "_Avg_df1")]], ties.method = "random")
  df_above_threshold$df2_Rank <- rank(-df_above_threshold[[paste0("Z_lm_", suffix, "_Avg_df2")]], ties.method = "random")
  
  list(z1 = z1, z2 = z2, df_above_threshold = df_above_threshold)
}

# Main execution function for a pairwise comparison
run_pairwise_comparison <- function(suffix, dir) {
  df <- load_and_merge_data(args$exp1_file, args$exp2_file)
  
  # Generate initial ontology-based plot
  generate_plot(df,
    paste0("Z_lm_", suffix, "_Avg_df1"), paste0("Z_lm_", suffix, "_Avg_df2"), "Ontology_Avg_df1",
    paste("Comparing Average GO Term Z lm for", args$exp1_name, "vs.", args$exp2_name),
    file.path(dir, paste0("Scatter_lm_GTA_Averages_", args$exp1_name, "_vs_", args$exp2_name, "_All_ByOntology")),
    theme_publication_legend_right)

  # Annotate interactions and generate overlap-based plot
  df <- annotate_interactions(df, args$exp1_name, args$exp2_name, suffix)
  ranks <- rank_and_filter_data(df, suffix)
  
  generate_plot(df,
    paste0("Z_lm_", suffix, "_Avg_df1"),
    paste0("Z_lm_", suffix, "_Avg_df2"),
    "Overlap_Avg",
    paste("Comparing Average GO Term Z lm for", args$exp1_name, "vs.", args$exp2_name),
    file.path(dir, paste0("Scatter_lm_GTA_Averages_", args$exp1_name, "_vs_", args$exp2_name, "_All_ByOverlap")),
    theme_publication_legend_right)

  generate_plot(ranks$df_above_threshold,
    paste0("Z_lm_", suffix, "_Avg_df1"),
    paste0("Z_lm_", suffix, "_Avg_df2"),
    "Overlap_Avg",
    paste("Comparing Average GO Term Z lm for", args$exp1_name, "vs.", args$exp2_name, "Above Threshold"),
    file.path(dir,
      paste0("Scatter_lm_GTA_Averages_", args$exp1_name, "_vs_", args$exp2_name, "_All_ByOverlap_AboveThreshold")),
    theme_publication_legend_right)
  
  # Save CSV files
  write.csv(df, file.path(dir,
    paste0("All_GTA_Avg_Scores_", args$exp1_name, "_vs_", args$exp2_name, ".csv")),
    row.names = FALSE)
  write.csv(ranks$df_above_threshold,
    file.path(dir, paste0("AboveThreshold_GTA_Avg_Scores_", args$exp1_name, "_vs_", args$exp2_name, ".csv")),
    row.names = FALSE)
}

# Execute Pairwise L and Pairwise K comparisons
run_pairwise_comparison("L", pairDirL)
run_pairwise_comparison("K", pairDirK)