#' @title A function to map WGBS methylation data to Illumina Probe IDs
#' @param probe_id_locations Either a dataframe or GRanges object containing
#' probe IDs and their locations. If dataframe: must contain columns named "ID",
#' "seqnames", "Start", "End", and "Strand". If GRanges: should have locations
#' ("seqnames", "ranges", "strand"), as well as metadata column "ID". Start and
#' end locations should be 1-based coordinates. Note that any row with NA values
#' will not be used.
#' @param WGBS_data Either a GRanges object or methylKit object (methylRaw,
#' methylBase, methylRawDB, or methylBaseDB) of CpG locations and their
#' methylation values. Contains locations ("seqnames", "ranges", "strand") and
#' metadata column(s) of methylation values of sample(s) (i.e. one column per
#' sample). These methylation values must be between 0 and 1.
#' @param cutoff The maximum number of basepairs distance to consider for probes
#' which have not been directly covered in the WGBS data. Default value is 10.
#' @param multipleMapping When searching for matches for probes not directly
#' covered in WGBS data, should WGBS CpGs which have already been mapped to
#' another probe still be considered? If TRUE, then yes. If FALSE, then no.
#' Default value is FALSE.
#' @importFrom methods is as
#' @importFrom tidyr drop_na
#' @importFrom GenomicRanges GRanges
#' @importFrom data.table nafill
#' @importFrom IRanges IRanges
#' @importFrom S4Vectors 'elementMetadata<-' runValue elementMetadata
#' @importFrom S4Vectors 'mcols<-' runValue mcols
#' @keywords mapping
#' @examples
#' data("IlluminaMethEpicB5ProbeIDs")
#' load(system.file("extdata", "WGBS_GRanges.rda", package = "deconvR"))
#' meth_probres <- BSmeth2Probe(
#' probe_id_locations = IlluminaMethEpicB5ProbeIDs,
#' WGBS_data = WGBS_GRanges
#' )
#' methp_cut <- BSmeth2Probe(
#' probe_id_locations = IlluminaMethEpicB5ProbeIDs,
#' WGBS_data = WGBS_GRanges[5:1000],
#' cutoff = 2
#' )
#' @return A dataframe with first column "IDs" for CpG IDs, then 1 or more
#' columns for methylation values of sample(s) (same number of samples as in
#' WGBS_data)
#' ID for each probe which was mapped, and then methylation value(s) of the
#' WGBS CpG to which it was matched (where either it overlapped or the gap was
#' < cutoff). If it matched to more than one CpG, the mean methylation value
#' is taken.
#' @export
BSmeth2Probe <- function(probe_id_locations, WGBS_data, cutoff = 10,
multipleMapping = FALSE) {
if (cutoff < 0) {
stop("cutoff must be >= 0")
}
if (NROW(probe_id_locations) == 0 || NROW(WGBS_data) == 0) {
stop("Probe ID locations or WGBS data must not be empty")
}
if (!(class(probe_id_locations) %in% c(
"data.frame", "GRanges"
))) {
stop("Probe IDs must be either dataframe or GRanges objects.")
}
if (!(class(WGBS_data) %in% c(
"GRanges", "methylRawList", "methylRaw", "methylRawListDB",
"methylBaseDB", "methylBase"
))) {
stop("WGBS_data must be either GRanges object or, a methylKit object,
such as methylBase, methylRawList, methylBaseDB")
}
if (is.data.frame(probe_id_locations)) {
names(probe_id_locations) <- vapply(names(probe_id_locations), tolower,
FUN.VALUE = character(1)
)
if (any(is.null(c("seqnames", "end", "start", "strand", "id") %in%
names(probe_id_locations)))) {
stop("probe_id_locations must contain columns named ID, Seqnames,
Start, End, and Strand.")
}
if (anyNA(probe_id_locations)) {
message("Dropping row containing NA: " +
which(is.na(probe_id_locations)))
probe_id_locations <- drop_na(probe_id_locations)
}
probe_id_locations <- GRanges(
seqnames = probe_id_locations[, "seqnames"],
## turn it into GRanges before continuing
ranges = IRanges(
start = probe_id_locations[, "start"],
end = probe_id_locations[, "end"]
),
strand = probe_id_locations[, "strand"],
ID = probe_id_locations[, "id"]
)
}
if (is(probe_id_locations, "GRanges")) {
if (is.null(probe_id_locations$ID)) {
stop("probe_id_locations must have metadata column ID")
}
}
# Convert methylKit objects to GRanges
if (!is(WGBS_data, "GRanges")) {
WGBS_data <- convertMe(WGBS_data)
}
if (is(WGBS_data, "GRanges")) {
column_names <- colnames(mcols(WGBS_data))
elementMetadata(WGBS_data) <-
nafill(as.data.frame(elementMetadata(WGBS_data)),
fill = 0
)
colnames(mcols(WGBS_data)) <- column_names
if (NCOL(elementMetadata(WGBS_data)) == 0) {
stop("WGBS_data must have at least one metadata column.")
}
if ((any(as.data.frame(elementMetadata(WGBS_data)) < 0)) ||
(any(as.data.frame(elementMetadata(WGBS_data)) > 1))) {
stop("The metadata columns of WGBS_data must contain methylation
values of sample(s) between 0 and 1")
}
}
allresults <- mapByOverlaps(
WGBS_data, probe_id_locations, cutoff,
multipleMapping
)
if (nrow(allresults) == 0) {
message("BSmeth2Probe couldn't find any match between the probe IDs and
WGBS data you have provided. Please make sure that you're using an
appropriate probe ID locations with your WGBS data.")
}
return(allresults)
}
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