R/LDmatrix.R

In LDlinkR: Calculating Linkage Disequilibrium (LD) in Human Population Groups of Interest

# LDlinkR::LDmatrix

#' Generates a data frame of pairwise linkage disequilibrium
#' statistics.
#'
#' @param snps list of between 2 - 2500 variants, using an rsID or chromosome coordinate (e.g. "chr7:24966446")
#' @param pop a 1000 Genomes Project population, (e.g. YRI or CEU), multiple allowed, default = "CEU"
#' @param r2d r2d, either "r2" for LD R2 or "d" for LD D', default = "r2"
#' @param token LDlink provided user token, default = NULL, register for token at \url{https://ldlink.nih.gov/?tab=apiaccess}
#' @param file Optional character string naming a path and file for saving results.  If file = FALSE, no file will be generated, default = FALSE.
#' @param genome_build Choose between one of the three options...`grch37` for genome build GRCh37 (hg19),
#' `grch38` for GRCh38 (hg38), or `grch38_high_coverage` for GRCh38 High Coverage (hg38) 1000 Genome Project
#' data sets.  Default is GRCh37 (hg19).
#' @param api_root Optional alternative root url for API.

#' @return a data frame
#' @importFrom httr GET content http_error stop_for_status
#' @importFrom utils capture.output read.delim write.table
#' @export
#'
#' @examples
#' \dontrun{LDmatrix(c("rs3", "rs4", "rs148890987"),
#'                   "YRI", "r2",
#'                   token = Sys.getenv("LDLINK_TOKEN"))
#'                  }
#'
LDmatrix <- function(snps,
                     pop="CEU",
                     r2d="r2",
                     token=NULL,
                     file = FALSE,
                     genome_build = "grch37",
                     api_root="https://ldlink.nih.gov/LDlinkRest") {

  LD_config <- list(ldmatrix_url=paste0(api_root,"/ldmatrix"),
                    avail_pop=c("YRI","LWK","GWD","MSL","ESN","ASW","ACB",
                                "MXL","PUR","CLM","PEL","CHB","JPT","CHS",
                                "CDX","KHV","CEU","TSI","FIN","GBR","IBS",
                                "GIH","PJL","BEB","STU","ITU",
                                "ALL", "AFR", "AMR", "EAS", "EUR", "SAS"),
                    avail_ld=c("r2", "d"),
                    avail_genome_build = c("grch37", "grch38", "grch38_high_coverage")
                   )


  url <- LD_config[["ldmatrix_url"]]
  avail_pop <- LD_config[["avail_pop"]]
  avail_ld <- LD_config[["avail_ld"]]
  avail_genome_build <- LD_config[["avail_genome_build"]]

  # ensure file option is a character string
  file <- as.character(file)

  # Define regular expressions used to check arguments for valid input below
  rsid_pattern <- "^rs\\d{1,}"
  # Syntax               Description
  # ^rs                  rsid starts with 'rs'
  # \\d{1,}              followed by 1 or more digits

  chr_coord_pattern <- "(^chr)(\\d{1,2}|X|x|Y|y):(\\d{1,9})$"
  # Syntax               Description
  # (^chr)               chromosome coordinate starts with 'chr'
  # (\\d{1,2}|X|x|Y|y)   followed by one or two digits, 'X', 'x', 'Y', 'y', to designate chromosome
  # :                    followed by a colon
  # (\\d{1,9})$          followed by 1 to 9 digits only to the end of string


  # Checking arguments for valid input
  if(length(snps) < 2 || length(snps) > 2500) {
    stop("Input is between 2 to 2500 variants.")
  }

  for(i in 1:length(snps)) {
    if(!((grepl(rsid_pattern, snps[i], ignore.case = TRUE)) | (grepl(chr_coord_pattern, snps[i], ignore.case = TRUE))))  {
      stop(paste("Invalid query format for variant: ",snps[i], ".", sep=""))
    }
  }

  if(!(all(pop %in% avail_pop))) {
    stop("Not a valid population code.")
  }

  if(!(r2d %in% avail_ld)) {
    stop("Not a valid r2d.  Enter 'r2' or 'd'.")
  }

  if(is.null(token)) {
    stop("Enter valid access token. Please register using the LDlink API Access tab: https://ldlink.nih.gov/?tab=apiaccess")
  }

  if(!(is.character(file) | file == FALSE)) {
    stop("Invalid input for file option.")
  }

  # Ensure input for 'genome_build' is valid.
  if(length(genome_build) > 1) {
    stop("Invalid input.  Please choose only one available genome build.")
  }

  if(!(all(genome_build %in% avail_genome_build))) {
    stop("Not an available genome build.")
  }

  # Request body
  snps_to_upload <- paste(unlist(snps), collapse = "\n")
  pop_to_upload <- paste(unlist(pop), collapse = "+")
  jsonbody <- list(snps=snps_to_upload, pop=pop_to_upload, r2_d=r2d, genome_build=genome_build)

  # URL string
  url_str <- paste(url, "?", "&token=", token, sep="")

  # Before 'POST command', check if LDlink server is up and accessible...
  # if server is down pkg should fail gracefully with informative message (not error)
  if (httr::http_error(url)) { # if server is down use message (and not an error)
    message("The LDlink server is down or not accessible. Please try again later.")
    return(NULL)
  } else { # network is up then proceed
    message("\nLDlink server is working...\n")
  }

  # POST command
  # raw_out <-  httr::POST(url=url_str, body=jsonbody, encode="json")
  raw_out <-  httr::POST(url=url_str, body=jsonbody, encode="json")
  httr::stop_for_status(raw_out)
  # Parse response object
  data_out <- read.delim(textConnection(httr::content(raw_out, "text", encoding = "UTF-8")), header=T, sep="\t")

  # Check for error in response data
  if(sum(grepl("error", data_out), na.rm = TRUE)) {
    # subset rows in data_out that contain text 'error'
    error_msg <- subset(data_out, grepl("error", data_out[,1], ignore.case = TRUE))

    # delete any column names so that they don't go to output
    names(error_msg) <- NULL

    error_msg <- paste(error_msg, collapse = " ")

    stop(error_msg)
  }

  # Evaluate 'file' option
  if (file == FALSE) {
    return(data_out)
  } else if (is.character(file)) {
    print(data_out)
    write.table(data_out, file = file, quote = F, row.names = F, sep = "\t")
    cat(paste("\nFile saved to ",file,".", sep=""))
    return(data_out)
  }

}
############ End Primary Function ##################