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scripts/parse_hughes_2006.R

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+library(tidyverse)
+library(here)
+library(arrow)
+library(readxl)
+
+# Constants ----
+GENOMIC_FEATURES_PATH <- here("data/genome_files/hf/features")
+HUGHES_DATA_DIR <- here("data/hughes_2006")
+
+# Load genomic features harmonization table ----
+# See https://huggingface.co/datasets/BrentLab/yeast_genome_resources
+genomicfeatures <- arrow::open_dataset(GENOMIC_FEATURES_PATH) %>%
+  as_tibble()
+
+#' Read and process Hughes normalized data
+#'
+#' @param path Path to Excel file
+#' @param ko Logical indicating if this is knockout data (TRUE) or overexpression (FALSE)
+#' @return Tibble with processed data
+read_hughes_normalized_data <- function(path, ko = TRUE) {
+  if (!file.exists(path)) {
+    stop("File not found: ", path)
+  }
+  df <- read_excel(path)
+  # Standardize first column name
+  colnames(df)[1] <- "hughes_target"
+  # Pivot to long format
+  df_long <- df %>%
+    pivot_longer(
+      cols = -hughes_target,
+      names_to = "sample",
+      values_to = "norm_log2fc"
+    ) %>%
+    mutate(norm_log2fc = as.numeric(norm_log2fc)) %>%
+    # remove deleted ORFs
+    filter(!hughes_target %in% c(
+      "YCL006C",
+      "YCR103C",
+      "YER187W-A"
+    )) %>%
+    # these are transposons/retrotransposons and just have
+    # typos
+    mutate(hughes_target = case_when(
+      hughes_target == "YDR034CD01" ~ "YDR034C-D",
+      hughes_target == "YDR210WD01" ~ "YDR210W-D",
+      hughes_target == "YDR261CD01" ~ "YDR261C-D",
+      hughes_target == "YGR161CD01" ~ "YGR161C-D",
+      hughes_target == "YPR158CD01" ~ "YPR158C-D",
+      .default = hughes_target
+    ))
+  # Process based on data type
+  if (ko) {
+    df_long = df_long %>%
+      separate(sample, into = c("prefix", "suffix"), sep = "/", remove = FALSE) %>%
+      mutate(
+        dye_orientation = str_extract(suffix, "[+-]$"),
+        regulator_symbol = str_to_upper(str_remove(suffix, "[+-]"))
+      ) %>%
+      select(-prefix, -suffix)
+  } else {
+    df_long = df_long %>%
+      mutate(
+        dye_orientation = str_extract(sample, "[+-]$"),
+        regulator_symbol = str_to_upper(str_remove(sample, "(-A)?OE[+-]"))
+      )
+  }
+
+  df_long %>%
+    select(-sample) %>%
+    pivot_wider(id_cols = c(regulator_symbol, hughes_target),
+                names_from = dye_orientation,
+                values_from = norm_log2fc) %>%
+    rename(dye_plus = `+`, dye_minus = `-`) %>%
+    rowwise() %>%
+    mutate(
+      mean_norm_log2fc = case_when(
+        # Both values are NA
+        is.na(dye_plus) & is.na(dye_minus) ~ NA_real_,
+        # Only one value is available - use that value
+        is.na(dye_plus) & !is.na(dye_minus) ~ dye_minus,
+        !is.na(dye_plus) & is.na(dye_minus) ~ dye_plus,
+        # Both values available but have opposite signs - average to zero
+        !is.na(dye_plus) & !is.na(dye_minus) & (sign(dye_plus) != sign(dye_minus)) ~ 0,
+        # Both values available with same sign - take the mean
+        TRUE ~ mean(c(dye_plus, dye_minus), na.rm = TRUE)
+      )
+    ) %>%
+    ungroup()
+}
+
+
+# Load and process data ----
+message("Loading knockout data...")
+df_ko <- read_hughes_normalized_data(
+  file.path(HUGHES_DATA_DIR, "Del_NormalizedRatios.xls"),
+  ko = TRUE
+)
+
+message("Loading overexpression data...")
+df_oe <- read_hughes_normalized_data(
+  file.path(HUGHES_DATA_DIR, "OE_NormalizedRatios.xls"),
+  ko = FALSE
+)
+
+message("Loading Z-scores...")
+zscore_df <- read_excel(file.path(HUGHES_DATA_DIR, "Z_SCORES_FOR_106_EXPERIMENTS.xls")) %>%
+  rename(hughes_target = `...1`) %>%
+  pivot_longer(
+    cols = -hughes_target,
+    names_to = "sample",
+    values_to = "zscore"
+  ) %>%
+  mutate(
+    perturbation = case_when(
+      str_detect(sample, "-D$") ~ "deletion",
+      str_detect(sample, "^OE") ~ "overexpression",
+      TRUE ~ "unknown"
+    ),
+    hughes_regulator = str_to_upper(str_remove(sample, "-D$|^OE"))
+  )
+
+# Load metadata ----
+message("Loading metadata...")
+hughes_2006_meta <- read_excel(file.path(HUGHES_DATA_DIR, "TRANSCRIPTION_FACTOR_LIST.xls")) %>%
+  rename(
+    regulator_locus_tag = Id_001,
+    regulator_symbol = Id_002
+  ) %>%
+  mutate(
+    essential = `Essential/Nonessential` == "essential",
+    oe_passed_qc = `OE passed QC` == "yes",
+    del_passed_qc = `DEL passed QC` == "yes"
+  ) %>%
+  select(-`Essential/Nonessential`, -ends_with("passed QC"))
+
+# Data validation ----
+message("Validating data consistency...")
+
+validate_data_consistency <- function() {
+  tests <- list(
+    # Check regulator locus tags match genomic features
+    regulator_locus_consistency = setequal(
+      intersect(genomic_features$locus_tag, hughes_2006_meta$regulator_locus_tag),
+      hughes_2006_meta$regulator_locus_tag
+    ),
+
+    # Check regulator symbols match genomic features
+    regulator_symbol_consistency = setequal(
+      intersect(genomic_features$symbol, hughes_2006_meta$regulator_symbol),
+      hughes_2006_meta$regulator_symbol
+    ),
+
+    # Check OE regulators match metadata
+    oe_regulator_consistency = setequal(
+      intersect(hughes_2006_meta$regulator_symbol, unique(df_oe$regulator_symbol)),
+      unique(df_oe$regulator_symbol)
+    ),
+
+    # Check KO regulators match metadata
+    ko_regulator_consistency = setequal(
+      intersect(hughes_2006_meta$regulator_symbol, unique(df_ko$regulator_symbol)),
+      unique(df_ko$regulator_symbol)
+    ),
+
+    # Check target consistency between KO and OE
+    target_consistency = setequal(
+      unique(df_ko$hughes_target),
+      unique(df_oe$hughes_target)
+    ),
+
+    # Check targets match genomic features
+    target_genomic_consistency = setequal(
+      unique(df_oe$hughes_target),
+      intersect(unique(df_oe$hughes_target), genomic_features$locus_tag)
+    )
+  )
+
+  # Report results
+  failed_tests <- names(tests)[!unlist(tests)]
+
+  if (length(failed_tests) == 0) {
+    message("✓ All validation tests passed")
+  } else {
+    stop("✗ Validation failed for: ", paste(failed_tests, collapse = ", "))
+  }
+
+  invisible(tests)
+}
+
+validate_data_consistency()
+
+# Summary statistics ----
+message("Data loading complete. Summary:")
+message("- Knockout experiments: ", length(unique(df_ko$regulator_symbol)), " regulators")
+message("- Overexpression experiments: ", length(unique(df_oe$regulator_symbol)), " regulators")
+message("- Target genes: ", length(unique(df_ko$hughes_target)))
+message("- Z-score experiments: ", length(unique(zscore_df$sample)))
+
+# Note about missing targets in Z-score data
+missing_targets_count <- length(setdiff(unique(df_ko$hughes_target),
+                                        unique(zscore_df$hughes_target)))
+if (missing_targets_count > 0) {
+  message("- Z-score data missing ", missing_targets_count, " targets present in KO/OE data")
+}
+
+missing_locus_tags <- setdiff(
+  unique(df_oe$hughes_target),
+  intersect(unique(df_oe$hughes_target), genomic_features$locus_tag)
+)
+
+genome_map = tibble(
+  locus_tag = intersect(unique(df_oe$hughes_target),
+                        genomic_features$locus_tag)) %>%
+  left_join(genomicfeatures %>% select(locus_tag, symbol)) %>%
+  mutate(hughes_target = locus_tag) %>%
+  bind_rows(
+    genomic_features %>%
+      filter(str_detect(alias, paste(missing_locus_tags, collapse = "|"))) %>%
+      mutate(alias_match = str_extract(alias, paste(missing_locus_tags, collapse = "|"))) %>%
+      dplyr::rename(hughes_target = alias_match) %>%
+      select(hughes_target, locus_tag, symbol)
+  ) %>%
+  dplyr::rename(target_locus_tag = locus_tag, target_symbol = symbol)
+
+stopifnot(setequal(genome_map$hughes_target, unique(df_oe$hughes_target)))
+
+df_oe_harmonized =
+  df_oe %>%
+  select(-c(sample, regulator_symbol)) %>%
+  pivot_wider(id_cols = c(regulator_symbol, hughes_target),
+              names_from = dye_orientation,
+              values_from = norm_log2fc) %>%
+  dplyr::rename(dye_plus = `+`, dye_minus = `-`) %>%
+  left_join(df_oe)
+  left_join(
+    select(hughes_2006_meta,
+           regulator_locus_tag,
+           regulator_symbol) %>%
+  left_join(genome_map) %>%
+  select(regulator_locus_tag, regulator_symbol,
+         target_locus_tag, target_symbol,
+         mean_log2fc)
+
+