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#' Get variants with mut_type from GRanges
#'
#' Get the variants of a certain mutation type from a GRanges or GRangesList object.
#' All other variants will be filtered out.
#' It is assumed that DBS/MBSs are called as separate SNVs.
#' They are merged into single variants.
#' The type of variant can be chosen with type.
#'
#' @param vcf_list GRanges/GRangesList
#' @param type The type of variant that will be returned.
#' @param predefined_dbs_mbs Boolean. Whether dbs and mbs variants have been
#' predefined in your vcf. This function by default assumes that dbs and mbs
#' variants are present in the vcf as snvs, which are positioned next to each
#' other. If your dbs/mbs variants are called separately you should set this
#' argument to TRUE. (default = FALSE)
#' @return GRanges/GRangesList of the desired mutation type.
#'
#' @examples
#' ## Get a GRanges list object.
#' ## See 'read_vcfs_as_granges' for more info how to do this.
#' grl <- readRDS(system.file("states/blood_grl.rds",
#' package = "MutationalPatterns"
#' ))
#'
#' ## Here we only use two samples to reduce runtime
#' grl <- grl[1:2]
#'
#' ## Get a specific mutation type.
#' snv_grl <- get_mut_type(grl, "snv")
#' indel_grl <- get_mut_type(grl, "indel")
#' dbs_grl <- get_mut_type(grl, "dbs")
#' mbs_grl <- get_mut_type(grl, "mbs")
#' @seealso
#' \code{\link{read_vcfs_as_granges}}
#'
#' @importFrom magrittr %>%
#' @export
get_mut_type <- function(vcf_list,
type = c("snv", "indel", "dbs", "mbs"),
predefined_dbs_mbs = FALSE) {
# Match argument
type <- match.arg(type)
if (predefined_dbs_mbs == FALSE & type != "indel"){
message(paste0("Any neighbouring SNVs will be merged into DBS/MBS variants.\n",
"Set the 'predefined_dbs_mbs' to 'TRUE' if you don't want this."))
}
# Turn grl into list.
if (inherits(vcf_list, "CompressedGRangesList")) {
vcf_list <- as.list(vcf_list)
}
# Get muttype per sample
if (inherits(vcf_list, "list")) {
grl <- purrr::map(vcf_list, .get_mut_type_gr, type, predefined_dbs_mbs) %>%
GenomicRanges::GRangesList()
return(grl)
} else if (inherits(vcf_list, "GRanges")) {
gr <- .get_mut_type_gr(vcf_list, type, predefined_dbs_mbs)
return(gr)
} else {
.not_gr_or_grl(vcf_list)
}
}
#' Get variants with mut_type from GRanges
#'
#' Get the variants of a certain mutation type from a GRanges object.
#' All other variants will be filtered out.
#' It is assumed that DBS/MBSs are called as separate SNVs.
#' They are merged into single variants.
#' The type of variant can be chosen with type.
#'
#' @param gr GRanges
#' @param type The type of variant that will be returned.
#' @param predefined_dbs_mbs Boolean. Whether DBS and MBS variants have been
#' predefined in your vcf. This function by default assumes that DBS and MBS
#' variants are present in the vcf as SNVs, which are positioned next to each
#' other. If your DBS/MBS variants are called separately you should set this
#' argument to TRUE. (default = FALSE)
#' @noRd
#'
#' @return GRanges of the desired mutation type.
#'
.get_mut_type_gr <- function(gr,
type = c("snv", "indel", "dbs", "mbs"),
predefined_dbs_mbs) {
# Match argument
type <- match.arg(type)
# Filter out bad variants
gr <- .remove_multi_alts_variants(gr)
# Indels
if (type == "indel") {
gr <- .remove_substitutions(gr)
return(gr)
}
# Substitutions
gr <- .remove_indels(gr)
if (predefined_dbs_mbs == TRUE) {
if (type == "snv"){
gr <- gr[width(.get_ref(gr)) == 1]
} else if (type == "dbs"){
gr <- gr[width(.get_ref(gr)) == 2]
} else if (type == "mbs"){
gr <- gr[width(.get_ref(gr)) >= 3]
}
return(gr)
}
if (predefined_dbs_mbs == FALSE) {
# Merge neighbouring SNVs into DBS and MBS variants. Then select the desired type.
gr_l <- .split_mbs_gr(gr)
not_mbs_f <- names(gr_l) %in% c(1, 2) # Determine which elements of the list are MNVs
if (type == "snv" & "1" %in% names(gr_l)) {
gr <- gr_l$`1`
} else if (type == "dbs" & "2" %in% names(gr_l)) {
gr <- gr_l$`2`
} else if (type == "mbs" & sum(!not_mbs_f) != 0) {
gr_l <- gr_l[!not_mbs_f]
gr <- unlist(GenomicRanges::GRangesList(gr_l))
} else { # Return empty gr when no variants are present.
gr <- gr[0]
}
return(gr)
}
}
#' Split SNV/MNV into SNV, DBS and MNVs of different sizes
#'
#' A function that splits a GRanges object into a list of GRanges.
#' Mutations are split based on whether they are a SNV/MNV. They are split based on their size.
#'
#'
#' This function assumes that a DBS/MNV is called as separate SNVs, that are located next to each other.
#' This function works by checking the location of these SNVs.
#' If multiple SNVs are located next to eachother they are considered a DBS/MNV.
#' A CAT>TAG would be considered as a MNV of length 3.
#' The largest variants are then selected and put into a separate GRanges object.
#' This is done recursively untill all variants are separated based on their size.
#' This way the CAT>TAG mutation will not be seen as two separate DBS variants.
#' This results in a list of granges.
#' If merge_muts is TRUE, then the SNVs that make up a DBS/MNV will be merged.
#'
#'
#' @param gr A GRanges object
#' @param merge_muts Boolean value. If TRUE, the mutations are merged.
#'
#' @noRd
#'
#' @return A list of granges
#' @importFrom magrittr %>%
#'
.split_mbs_gr <- function(gr, merge_muts = TRUE) {
# These variables use non standard evaluation.
# To avoid R CMD check complaints we initialize them to NULL.
. <- NULL
# Validate input
.check_no_indels(gr)
# Return empty grl when initial input is empty
if (!length(gr)) {
return(GRangesList(gr))
}
# Sort
gr <- BiocGenerics::sort(gr)
# Identify location of each mut and its subsequent mut.
chroms <- GenomeInfoDb::seqnames(gr) %>%
as.vector()
first_chrom <- chroms[-length(chroms)]
second_chrom <- chroms[-1]
coords <- BiocGenerics::start(gr)
first_coords <- coords[-length(coords)]
second_coords <- coords[-1]
# Compare location of mut and subsequent mut. If they are only one base apart then they are sequential.
# Sequential forms a boolean vector. A 1 means the mutations is sequential to the previous one
sequential <- first_chrom == second_chrom & first_coords + 1 == second_coords
sequential <- c(0, sequential)
# Sequence is a numeric vector. A n means that a mutations is the Nth sequential base in a mutations.
# Example: 0100123. Here the second mutation is sequential to the first. So the first two muts are a DBS.
# Next is a sbs. Then there is another 0 and then 3 sequential muts. This means that together they form a 4 base substitution.
seq_rle <- rle(sequential)
sequence <- sequence(seq_rle$lengths)
sequence[sequential == 0] <- 0
# Find the maximum number of sequential mutations. (This is one less than the final mut size. So 1 for a DBS.)
max_seq_l <- max(sequence)
mut_l <- max_seq_l + 1
# Find the locations of the variants with this mut size
end_i_muts <- which(max_seq_l == sequence)
start_i_muts <- end_i_muts - max_seq_l
full_muts_i_l <- purrr::map2(start_i_muts, end_i_muts, seq)
full_muts_i <- unlist(full_muts_i_l)
# Merge DBS and MBS if the user wants this.
if (mut_l != 1 & merge_muts == TRUE) {
gr_sub <- purrr::map(full_muts_i_l, function(i_v) .merge_muts(gr[i_v])) %>%
do.call(base::c, .)
} else {
gr_sub <- gr[full_muts_i]
}
# Put the mutations with the largest mutsize in a list
gr_l <- list(gr_sub)
names(gr_l) <- mut_l
# Recurse on the rest of the mutations if there are still smaller mutations left.
gr <- gr[-full_muts_i]
if (length(gr) == 0) {
return(gr_l)
} else {
gr_l_deeper <- .split_mbs_gr(gr)
gr_l <- c(gr_l, gr_l_deeper)
}
return(gr_l)
}
#' Merge variants in a GRanges object.
#'
#' Merge all variants in a GRanges object into a single variant.
#' This is usefull when a DBS/MNV is called as separate SNVs.
#'
#' @param gr GRanges object
#'
#' @noRd
#'
#' @return GRanges object with a single variant.
.merge_muts <- function(gr) {
# Check input gr
.check_no_indels(gr)
# Use position and other values of the first mut.
gr_new <- gr[1]
# Combine refs, alts and quals
gr_new$REF <- gr %>%
.get_ref() %>%
as.vector() %>%
stringr::str_c(collapse = "") %>%
Biostrings::DNAStringSet()
gr_new$ALT <- gr %>%
.get_alt() %>%
unlist() %>%
as.vector() %>%
stringr::str_c(collapse = "") %>%
Biostrings::DNAStringSetList()
gr_new$QUAL <- mean(gr$QUAL, na.rm = TRUE)
# Return the new gr
names(gr_new) <- ""
return(gr_new)
}
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