R/LDpair.R

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

# LDlinkR::LDpair

########## Function for Output option "Table" ##############
table_out <- function (data_out) {
# Tidy up data_out
z <- strsplit(data_out[,1], "\\s+")

# Create new 'table' from elements of data_out
df_pair_tbl <- data.frame(var1 = z[[1]][1],
                          var2 = z[[2]][1],
                          pops = z[[3]][1],
                          var1_pos = substr(z[[1]][2], 2, (nchar(z[[1]][2]))-1),
                          var2_pos = substr(z[[2]][2], 2, (nchar(z[[2]][2]))-1),
                          var1_a1 = z[[7]][2],
                          var1_a2 = z[[9]][2],
                          var1_a1_freq = as.numeric(substr(z[[7]][9], 2, (nchar(z[[7]][9]))-1)),
                          var1_a2_freq = as.numeric(substr(z[[9]][9], 2, (nchar(z[[9]][9]))-1)),
                          var2_a1 = z[[5]][2],
                          var2_a2 = z[[5]][3],
                          var2_a1_freq = as.numeric(substr(z[[12]][2], 2, (nchar(z[[12]][2]))-1)),
                          var2_a2_freq = as.numeric(substr(z[[12]][3], 2, (nchar(z[[12]][3]))-1)),
                          d_prime = as.numeric(z[[17]][3]),
                          r2 = as.numeric(z[[18]][3]),
                          chisq = as.numeric(z[[19]][3]),
                          p_val = as.numeric(substr(z[[20]][3], 2, (nchar(z[[20]][3])))),
                          stringsAsFactors = FALSE
                         )

 if (nrow(data_out) == 22) {
   if (grepl("warning", z[[22]][1], ignore.case = TRUE))  {
     # Add these two columns to df_pair_tbl, if there is a "warning" message in data_out
     df_pair_tbl$ld <- paste(z[[21]], collapse = " ")
     df_pair_tbl$note <- paste(z[[22]], collapse = " ")

   } else {
     # Used if no "warning" message in data_out
     df_pair_tbl$corr_alleles <- paste(z[[21]][1], "-", z[[21]][6], ", ", z[[22]][1], "-", z[[22]][6], sep="")
   }

 } else {
   df_pair_tbl$ld <- paste(z[[21]], collapse = " ")
 }

 return(df_pair_tbl)
}
################ End Function ##############################


###### Primary Function #######
#' Investigates potentially correlated alleles for a
#' pair of variants.
#'
#' @param var1 the first RS number or genomic coordinate (e.g. "chr7:24966446")
#' @param var2 the second RS number or genomic coordinate (e.g. "ch7:24966446")
#' @param pop a 1000 Genomes Project population(s), (e.g. YRI or CEU), multiple allowed, default = "CEU"
#' @param token LDlink provided user token, default = NULL, register for token at  \url{https://ldlink.nih.gov/?tab=apiaccess}
#' @param output two output options available, "text", which displays a two-by-two matrix displaying haplotype counts and allele frequencies along with other statistics, or "table", which displays the same data in rows and columns, default = "table"
#' @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 text or data frame, depending on the output option
#' @importFrom httr GET content stop_for_status http_error
#' @importFrom utils capture.output read.delim write.table
#' @export
#'
#' @examples
#' \dontrun{LDpair(var1 = "rs3", var2 = "rs4", pop = "YRI", token = Sys.getenv("LDLINK_TOKEN"))}
#' \dontrun{LDpair("rs3", "rs4", "YRI", token = Sys.getenv("LDLINK_TOKEN"), "text")}
#'
LDpair <- function(var1,
                   var2,
                   pop = "CEU",
                   token=NULL,
                   output = "table",
                   file = FALSE,
                   genome_build = "grch37",
                   api_root="https://ldlink.nih.gov/LDlinkRest") {

LD_config <- list(ldpair_url=paste0(api_root,"/ldpair"),
                  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_output=c("text", "table"),
                  avail_genome_build = c("grch37", "grch38", "grch38_high_coverage")
                 )


  url <- LD_config[["ldpair_url"]]
  avail_pop <- LD_config[["avail_pop"]]
  avail_output <- LD_config[["avail_output"]]
  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(var1) == 1)) {
    stop("Input one SNP for Variant 1 only.")
  }

  if(!(length(var2) == 1)) {
    stop("Input one SNP for Variant 2 only.")
  }

  if(!((grepl(rsid_pattern, var1, ignore.case = TRUE)) | (grepl(chr_coord_pattern, var1, ignore.case = TRUE)))) {
    stop(paste("Invalid query SNP format for Variant 1: ",var1,".", sep=""))
  }

   if(!((grepl(rsid_pattern, var2, ignore.case = TRUE)) | (grepl(chr_coord_pattern, var2, ignore.case = TRUE)))) {
     stop(paste("Invalid query SNP format for Variant 2: ",var2,".", sep=""))
  }

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

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

  if(!(all(output %in% avail_output))) {
    stop("Not a valid output option. Please specify either \"text\" or \"table\".")
  }

  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
  pop_to_upload <- paste(unlist(pop), collapse = "%2B")
  body <- list(paste("var1=", var1, sep=""),
               paste("var2=", var2, sep=""),
               paste("pop=", pop_to_upload, sep=""),
               paste("genome_build=", genome_build, sep=""),
               paste("json_out=", "false", sep=""), # See LDlink API Access documentation
               paste("token=", token, sep=""))

# URL query string
  url_str <- paste(url, "?", paste(unlist(body), collapse = "&"), sep="")

# before 'GET 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")
}

# GET command, request to the web server
raw_out <- httr::GET(url=url_str)
httr::stop_for_status(raw_out)
# Parse response object from web server
data_out <- read.delim(textConnection(httr::content(raw_out, "text", encoding = "UTF-8")), header=T, as.is = T, sep="\t")

# Check for error/warning in response data
if(sum(grepl("error", data_out, ignore.case = TRUE), 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)
}

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

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

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

  message(warning_msg)
}

# Evaluate 'output' option for either "text" or "table"
  if(output == "text") {
    if(file == FALSE) {
      cat(httr::content(raw_out, "text"))
    } else if (is.character(file)) {
      cat(httr::content(raw_out, "text"))
      writeLines(capture.output(cat(httr::content(raw_out, "text"))), "text_out.txt")
      cat(paste("\nFile saved to ","text_out.txt",".", sep=""))
     }
  } else if (output == "table") {
    if(file == FALSE) {
      data_out_tbl <- table_out(data_out)
      return(data_out_tbl)
    } else if (is.character(file)) {
      data_out_tbl <- table_out(data_out)
      print(data_out_tbl)
      write.table(data_out_tbl, file = "table_out.txt", quote = F, row.names = F, sep = "\t")
      cat(paste("\nTable saved to ","table_out.txt",".", sep=""))
      return(data_out_tbl)
    }
  }

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