R/investigate_target.R

In AliSajid/DrugDiscoveryPanCan: Investigate Drug Targets for Kinase Therapies

#' Investigate a Given Gene or Drug
#'
#' This function takes the name of a gene or a drug and a database to use to pull signatures
#' from and then queries iLINCS to get concordant signatures
#'
#' @param target The name of the gene or drug
#' @param input_lib One of "OE", "KD" or "CP". Marks the database to use.
#' @param output_lib One of "OE", "KD" or "CP". Marks the database to query.
#' @param filter_threshold The Filtering threshold.
#' @param similarity_threshold The Similarity Threshold
#' @param paired Logical. Whether to query iLINCS separately for up and down regulated genes
#' @param input_cell_lines A character vector of cell lines to restrict our search for input signatures to.
#' @param output_cell_lines A character vetor of cell lines to restrict the output search to.
#' @param discordant Logical. Whether to look for discordant signatures
#'
#' @return A tibble with the the similarity scores and signature metadata
#' @export
#'
#' @importFrom dplyr filter pull select any_of inner_join
#' @importFrom stringr str_to_lower
#' @importFrom purrr map map2 map_dfr
#' @importFrom rlang .data
#'
#' @examples
#' TRUE
investigate_target <- function(target, input_lib, output_lib,
                               filter_threshold = 0.85, similarity_threshold = 0.321,
                               paired = TRUE, input_cell_lines = NULL,
                               output_cell_lines = NULL, discordant = FALSE) {

  libs <- c("OE", "KD", "CP")

  if(!input_lib %in% libs | !output_lib %in% libs) {
    stop("Both input and output libraries must be one of 'OE', 'KD', 'CP'")
  }

  if (missing(input_lib) | missing(output_lib)) {
    stop("Please specify both input and output libraries")
  }

  if (input_lib == "OE") {
    input_metadata <- oe_metadata
  } else if (input_lib == "KD") {
    input_metadata <- kd_metadata
  } else if (input_lib == "CP") {
    input_metadata <- cp_metadata
  } else {
    stop("Invalid input_lib")
  }


  if (!is.null(input_cell_lines)) {
    filtered_signature_ids <- input_metadata %>%
      dplyr::filter(stringr::str_to_lower(target) == stringr::str_to_lower(.data$Source)) %>%
      dplyr::filter(.data$SourceCellLine %in% input_cell_lines) %>%
      dplyr::pull(.data$SourceSignature)
  } else {
    filtered_signature_ids <- input_metadata %>%
      dplyr::filter(stringr::str_to_lower(target) == stringr::str_to_lower(.data$Source)) %>%
      dplyr::pull(.data$SourceSignature)
  }

  if (length(filtered_signature_ids) == 0) {
    stop("No signatures match the given input criteria.")
  }

  all_signatures <- filtered_signature_ids %>%
    purrr::map(~ get_signature(.x))

  if (paired) {
    filtered_up <- all_signatures %>%
      purrr::map(~ filter_signature(.x, direction = "up", threshold = filter_threshold))

    filtered_down <- all_signatures %>%
      purrr::map(~ filter_signature(.x, direction = "down", threshold = filter_threshold))

    concordant_up <- filtered_up %>%
      purrr::map(~ get_concordants(.x, library = output_lib))

    concordant_down <- filtered_down %>%
      purrr::map(~ get_concordants(.x, library = output_lib))

    consensus_targets <- purrr::map2(concordant_up, concordant_down,
                                     ~ consensus_concordants(.x, .y, paired = paired,
                                                             cell_line = output_cell_lines,
                                                             discordant = discordant))
  } else {
    filtered <- all_signatures %>%
      purrr::map(~ filter_signature(.x, direction = "any", threshold = filter_threshold))

    concordants <- filtered %>%
      purrr::map(~ get_concordants(.x, library = output_lib))

    consensus_targets <- purrr::map(concordants,
                                    ~ consensus_concordants(.x, paired = paired,
                                                            cell_line = output_cell_lines,
                                                            discordant = discordant,
                                                            cutoff = similarity_threshold))
  }

  augmented <- consensus_targets %>%
    purrr::map2(filtered_signature_ids, ~ dplyr::mutate(.x, SourceSignature = .y)) %>%
    purrr::map_dfr(~ dplyr::inner_join(.x, input_metadata, by = "SourceSignature")) %>%
    dplyr::select(.data$Source, .data$Target, .data$Similarity,
                  .data$SourceSignature, .data$SourceCellLine,
                  dplyr::any_of(c("SourceConcentration")), .data$SourceTime,
                  .data$TargetSignature, .data$TargetCellLine,
                  dplyr::any_of(c("TargetConcentration")), .data$TargetTime)

  augmented
}