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parse_one_substitute <- function(aaChg, wt.sequence, offset=0, seq.lim=1001) {
if (is.na(wt.sequence)) {
ref = NA
pos = NA
alt = NA
wt = NA
sequence = NA
sequence.len = NA
seq.start = NA
seq.end = NA
pos.orig = NA
sequence.orig = NA
wt.orig = NA
sequence.len.orig = NA
} else {
protein.dictionary <- c(
"A"="Ala", "R"="Arg", "N"="Asn", "D"="Asp", "C"="Cys", "Q"="Gln", "E"="Glu",
"G"="Gly", "H"="His", "I"="Ile", "L"="Leu", "K"="Lys", "M"="Met", "F"="Phe",
"P"="Pro", "O"="Pyl", "S"="Ser", "U"="Sec", "T"="Thr", "W"="Trp", "Y"="Tyr",
"V"="Val", "B"="Asx", "Z"="Glx", "X"="Xaa", "J"="Xle"
)
protein.reverse.dictionary <- names(protein.dictionary)
names(protein.reverse.dictionary) <- protein.dictionary
pos_raw <- regmatches(aaChg, gregexpr('[0-9]+', aaChg))[[1]]
pos <- as.numeric(pos_raw) + offset
if (length(pos) == 0) {
# probably synonymous variant
ref <- NA
pos <- NA
alt <- NA
if (aaChg == "p.=" | aaChg == "p.(=)" | aaChg == "_wt") {
newseq <- wt.sequence
} else {
newseq <- NA
}
} else if (length(pos) == 2 & !grepl('fs', aaChg)) {
# probably delins
ref_aa_start <- strsplit(substr(aaChg, 3,
nchar(aaChg)),
split = pos_raw[1])[[1]][1]
remains <- strsplit(substr(aaChg, 3,
nchar(aaChg)),
split = pos_raw[1])[[1]][2]
ref_aa_end <- strsplit(substr(remains, 2,
nchar(remains)),
split = pos_raw[2])[[1]][1]
remains <- strsplit(substr(remains, 2,
nchar(remains)),
split = pos_raw[2])[[1]][2]
if (remains == "del") {
alt <- ""
} else {
alt <- strsplit(remains, split = 'delins')[[1]][2]
}
if (nchar(ref_aa_start) > 1) {
ref_aa_start <- as.character(protein.reverse.dictionary[ref_aa_start])
}
if (nchar(ref_aa_end) > 1) {
ref_aa_end <- as.character(protein.reverse.dictionary[ref_aa_end])
}
if (nchar(alt) > 1) {
alt <- as.character(protein.reverse.dictionary[alt])
}
if (ref_aa_start == substr(wt.sequence, pos[1], pos[1]) &
ref_aa_end == substr(wt.sequence, pos[2], pos[2])) {
newseq <- wt.sequence
ref <- substr(wt.sequence, pos[1], pos[2])
substr(newseq, pos[1], pos[1]) <- alt
for (i in (pos[1]+1):pos[2]) {
newseq <- paste(unlist(strsplit(newseq, ""))[-(pos[1]+1)], collapse = "")
}
pos <- pos[1]
} else {
ref <- substr(wt.sequence, pos[1], pos[2])
alt <- NA
newseq <- NA
pos <- NA
}
} else if (length(pos) == 2 & grepl('fs', aaChg)) {
pos <- pos[1]
ref <- substr(wt.sequence, pos, pos)
alt <- NA
newseq <- NA
} else if (pos > nchar(wt.sequence)) {
# out of bound
ref <- NA
pos <- pos
alt <- NA
if (aaChg == "p.=" | aaChg == "p.(=)" | aaChg == "_wt") {
newseq <- wt.sequence
} else {
newseq <- NA
}
} else {
# possible missense variant
ref_alt_raw <- strsplit(substr(aaChg, 3,
nchar(aaChg)),
split = pos_raw)[[1]]
ref <- ref_alt_raw[1]
if (nchar(ref) > 1) {
ref <- as.character(protein.reverse.dictionary[ref])
}
if (ref == substr(wt.sequence, pos, pos)) {
newseq <- wt.sequence
if (ref_alt_raw[2] == "~" | ref_alt_raw[2] == "del") {
alt <- NA
newseq <- paste(unlist(strsplit(wt.sequence, ""))[-pos], collapse = "")
} else if (ref_alt_raw[2] == "*" | ref_alt_raw[2] == "Ter") {
alt <- NA
newseq <- substr(wt.sequence, 1, pos-1)
} else if (ref_alt_raw[2] == "=") {
# do nothing
alt <- NA
} else {
alt <- ref_alt_raw[2]
if (nchar(alt) > 1) {
alt <- as.character(protein.reverse.dictionary[alt])
}
substr(newseq, pos, pos) <- alt
}
} else {
ref <- substr(wt.sequence, pos, pos)
alt <- NA
newseq <- NA
}
}
if (!is.na(newseq) & nchar(newseq)<=1) {
newseq <- NA
}
# crop sequence depends on sequence length
sequence.len.orig <- nchar(newseq)
sequence.orig <- newseq
pos.orig <- pos
wt.orig <- wt.sequence
if (!is.na(sequence.len.orig) &
!is.na(pos.orig) &
(sequence.len.orig > seq.lim | nchar(wt.orig) > seq.lim)) {
sequence.len <- seq.lim
if (pos.orig < (seq.lim+1)/2) {
sequence <- substr(sequence.orig, 1, seq.lim)
wt <- substr(wt.orig, 1, seq.lim)
pos <- pos.orig
seq.start <- 1
seq.end <- seq.lim
} else if (pos.orig + (seq.lim-1)/2 > sequence.len.orig) {
sequence <- substr(sequence.orig,
sequence.len.orig-seq.lim+1,
sequence.len.orig)
wt <- substr(wt.orig,
sequence.len.orig-seq.lim+1,
sequence.len.orig)
pos <- pos.orig - sequence.len.orig + seq.lim
seq.start <- sequence.len.orig - seq.lim + 1
seq.end <- sequence.len.orig
} else {
sequence <- substr(sequence.orig,
pos.orig-(seq.lim-1)/2,
pos.orig+(seq.lim-1)/2)
wt <- substr(wt.sequence,
pos.orig-(seq.lim-1)/2,
pos.orig+(seq.lim-1)/2)
pos <- (seq.lim+1)/2
seq.start <- pos.orig-(seq.lim-1)/2
seq.end <- pos.orig+(seq.lim-1)/2
}
} else {
sequence.len <- sequence.len.orig
sequence <- sequence.orig
wt <- wt.sequence
pos <- pos.orig
seq.start <- 1
seq.end <- sequence.len.orig
}
}
result <- list(ref=ref, pos=pos, alt=alt,
wt = wt,
sequence = sequence,
sequence.len = sequence.len,
seq.start = seq.start,
seq.end = seq.end,
pos.orig = pos.orig,
sequence.orig = sequence.orig,
wt.orig = wt.orig,
sequence.len.orig = sequence.len.orig)
result
} |