#' BeeMarkov
#'
#' A package to study markov chains.
#'
#' @docType package
#' @name beemarkov
NULL
#' @import graphics
#' @import seqinr
#' @import utils
NULL
#' transition
#'
#' Compute the transition model for one Markov model on DNA.
#'
#' @param file a file (fasta) to read and use as training for model
#' @param l_word length of words for the model. Equal to the "order of the model + 1"
#' @param n_seq number of sequences to train the model with
#' @param log boolean information if the transition matrix of the model is in log or not.
#' @param type a indicator ("+" or "-") for printing pretty stuff during computations
#'
#'
#' @author Jaunatre Maxime <maxime.jaunatre@etu.univ-grenoble-alpes.fr>
#'
#' @export
transition <- function(file, # fichier
l_word = 1, # longueur des mots
n_seq = 1, # Nombre de sequences a analyser
log = TRUE,
type = "") {
seq <-seqinr::read.fasta(file)
Nseq <- length(seq)
if (Nseq < n_seq) { # check if user want to input too many seq in the matrix learning
stop(paste("n_seq is larger than the number of sequence in this file ( ", Nseq, " sequences for this file).", sep = ""))
}
l <- sapply(seq, length)
if (l_word > min(l) | l_word >= 10) {
stop("This is really too much for me, abort!!!")
}
tmp <-seqinr::count(seq[[1]], l_word) + 1 # add 1 occurence to have at least 1 obs
cat(paste(" ============ Training model M",type,l_word," ============ \n", sep = ""))
pb <- utils::txtProgressBar(min = 0, max = n_seq, style = 3)
for (i in 2:n_seq) {
utils::setTxtProgressBar(pb, i)
tmp <- tmp +seqinr::count(seq[[i]], l_word)
}
close(pb)
# # alternativ way, slower but prettier
# cat(paste(" ============ Training model M",type,l_word," ============ \n", sep = ""))
# l_count = function(Seq,n = l_word){count(Seq,n)}
# tmp <- rowSums(sapply(seq,l_count))
if (l_word>1) {
i <- 1
wind = 4
for(j in 0:((length(tmp)/wind)-1)){
tmp[(1+wind*j):(wind+wind*j)] <- tmp[(1+wind*j):(wind+wind*j)] * 4^(i-1) / sum(tmp[(1+wind*j):(wind+wind*j)] )
}
cat(' ============ Computing conditionnal probabilities ============ \n')
} else {
tmp = tmp / sum(tmp)
}
# possibility to compute without log
if (log) {
tmp = log(tmp)
}
return(tmp)
}
#' quality
#'
#' Compute the quality of the model and return a TRUE Positive or FALSE Negative information.
#' It test the positive and negative model and assign every sequence of the fasta file to one model or the other.
#' Therefore, the file must countain sequences which are know to be from one model.
#'
#' @param file a file (fasta) to read and use to test model
#' @param pos_training a file (fasta) to read and train the positive model
#' @param neg_training a file (fasta) to read and train the negative model
#' @param trans_pos a transition matrix if it was already computed. Therefore, no need to train models. Warning, it must be in log
#' @param trans_neg a transition matrix if it was already computed. Therefore, no need to train models. Warning, it must be in log
#' @param l_word_pos length of words for the model. Equal to the "order of the model + 1"
#' @param l_word_neg length of words for the model. Equal to the "order of the model + 1"
#' @param n_train number of sequences to train with
#' @param n_seq number of sequences to analyse
#' @param quiet if some informations are print or not (boolean)
#'
#'
#' @author Jaunatre Maxime <maxime.jaunatre@etu.univ-grenoble-alpes.fr>
#'
#' @export
quality <- function(file, # fichier
pos_training = NULL, # file to train with for positive
neg_training = NULL, # file to train with for negative
trans_pos = NULL, #transition matrice pos
trans_neg = NULL, #transition matrice pos
l_word_pos = 1, # word lenght for transition table positif
l_word_neg = 1, # word length for transition table negatif
n_train = 1, # number of sequences to train with
n_seq = 1, # number of sequences to analyse
quiet = FALSE
){
if(is.null(c(trans_pos,trans_neg))){
trans_pos <-transition(file = pos_training, n_seq = n_train, l_word = l_word_pos, type ="+")
trans_neg <- transition(file = neg_training, n_seq = n_train, l_word = l_word_neg, type = "-")
}
seq <-seqinr::read.fasta(file)
Nseq <- length(seq)
if(Nseq < n_seq){ # check if user want to input too many seq in the matrix learning
stop(paste("n_seq is larger than the number of sequence in this file ( ",Nseq," sequences for this file).", sep = ""))
}
result <- data.frame(VP = rep(FALSE,n_seq),
FN = rep(TRUE,n_seq),
pos = rep(NA,n_seq),
neg = rep(NA,n_seq)
)
p_init_pos = log(1/4^l_word_pos)
p_init_neg = log(1/4^l_word_neg)
if(!quiet) {cat(' ============ Computing sensi and speci for the test sequences ============ \n')
pb <- utils::txtProgressBar(min = 0, max = n_seq, style = 3)}
for(i in 1:n_seq){
if(!quiet) utils::setTxtProgressBar(pb, i)
n_word_pos <-seqinr::count(seq[[i]], l_word_pos)
n_word_neg <-seqinr::count(seq[[i]], l_word_neg)
result$pos[i] <- p_init_pos + sum( trans_pos * n_word_pos )
result$neg[i] <- p_init_neg + sum( trans_neg * n_word_neg )
if(result$pos[i] > result$neg[i]){
result$VP[i] <- TRUE ; result$FN[i] <- FALSE
} else {
result$VP[i] <- FALSE ; result$FN[i] <- TRUE
}
}
if(!quiet) close(pb)
tmp <- colSums(result[,1:2])
return(tmp)
}
#' threshold
#'
#' Compute the quality for multiple set of values in vectors.
#' Compute TRUE Positive or FALSE Negative information and FALSE Positive and TRUE Negative.
#' All of this allow to compute sensitivoty and specificity of every model.
#'
#' Compute the quality of the model and return a TRUE Positive or FALSE Negative information.
#' It test the positive and negative model and assign every sequence of the fasta file to one model or the other.
#' Therefore, the file must countain sequences which are know to be from one model.
#'
#' @param pos_test a file (fasta) to read and use to test positive model
#' @param neg_test a file (fasta) to read and use to test negative model
#' @param pos_training a file (fasta) to read and train the positive model
#' @param neg_training a file (fasta) to read and train the negative model
#' @param pos_seq a vector for lengths of words for the model. Equal to the "order of the model + 1"
#' @param neg_seq a vector fof lengths of words for the model. Equal to the "order of the model + 1"
#' @param n_train number of sequences to train with
#' @param n_seq number of sequences to analyse
#'
#'
#' @author Jaunatre Maxime <maxime.jaunatre@etu.univ-grenoble-alpes.fr>
#'
#' @export
threshold <- function(pos_test, # fichier
neg_test,
pos_training, # file to train with for positive
neg_training, # file to train with for negative
pos_seq = c(1:2),
neg_seq = c(1:2),
n_train = 1, # number of sequences to train with
n_seq = 1 # number of sequences to analyse
){
# choix =utils::menu(c("yes","no"),
# title = "You will launch long computation, do you wish to procede further ?")
# if (choix ==1) cat("\n ============ Go take a good coffee ============ \n\n")
# if (choix ==2) stop("You stopped the computations")
trans_pos <- list()
trans_neg <- list()
cat('\n ============ Training modeles ============ \n\n')
for(i in pos_seq){
trans_pos[[i]] <- transition(file = pos_training, n_seq = n_train, l_word = i, type = "+")
}
cat('\n')
for(j in neg_seq){
trans_neg[[j]] <- transition(file = neg_training, n_seq = n_train, l_word = j, type = "-")
}
cat('\n ============ Training modeles ============ \n\n')
sensi <- speci <- matrix(rep(0,length(pos_seq)*length(neg_seq)),ncol = length(pos_seq),nrow = length(neg_seq))
for(i in pos_seq){
for(j in neg_seq){
cat('\n')
cat(paste(" ============ Model M+ (",i,"/",j,") ============ \n", sep = ""))
pos <- quality(file = pos_test, # fichier
trans_pos = trans_pos[[i]], #transition matrice pos
trans_neg = trans_neg[[j]], #transition matrice neg
l_word_pos = i, # transition table positif
l_word_neg = j, # transition table negatif
n_train = n_train, # number of sequences to train with
n_seq = n_seq, # number of sequences to analyse
quiet = TRUE
)
cat(paste(" ============ Model M- (",i,"/",j,") ============ \n", sep = ""))
neg <- quality(file = neg_test, # fichier
trans_pos = trans_pos[[i]], #transition matrice pos
trans_neg = trans_neg[[j]], #transition matrice neg
l_word_pos = i, # transition table positif
l_word_neg = j, # transition table negatif
n_train = n_train, # number of sequences to train with
n_seq = n_seq, # number of sequences to analyse
quiet = TRUE
)
sensi[i,j] <- pos[1] / sum(pos)
speci[i,j] <- neg[2] / sum(neg)
}
}
cat(paste(" ============ Come back from your coffee ============ \n", sep = ""))
colnames(sensi) <- colnames(speci) <- paste("-",neg_seq, sep="")
rownames(sensi) <- rownames(speci) <- paste("+",pos_seq, sep="")
final <-list(sensi,speci) ; names(final) = c("sensi","speci")
return(final)
}
#' viterbi
#'
#' Compute a data.frame explaining loglikelyhood of every base of a sequence
#' with a Viterbi algorithme based of a model of transition between 2 different models. These models are
#' trained with 2 differents datasets.
#'
#' @param file a file (fasta) to read and to run viterbi on
#' @param pos_training a file (fasta) to read and train the positive model
#' @param neg_training a file (fasta) to read and train the negative model
#' @param l_word_pos a value for lengths of words for the model. Equal to the "order of the model + 1"
#' @param l_word_neg a value fof lengths of words for the model. Equal to the "order of the model + 1"
#' @param n_train number of sequences to train with
#' @param n_ana number of sequences to analyse
#' @param l_c mean length of a CpG+ region
#' @param l_nc mean length of a CpG- region
#'
#'
#' @author Jaunatre Maxime <maxime.jaunatre@etu.univ-grenoble-alpes.fr>
#'
#' @export
viterbi <- function(file,
pos_training = "raw_data/mus_cpg_app.fa", # file to train with for positive
neg_training = "raw_data/mus_tem_app.fa", # file to train with for negative
l_word_pos = 1,
l_word_neg = 1,
n_train = 1160,
n_ana = 1,
l_c = 1000, # length coding
l_nc = 125000 # length non-coding
) {
trans_pos <- transition(file = pos_training, n_seq = n_train, l_word = l_word_pos, type = "+")
trans_neg <- transition(file = neg_training, n_seq = n_train, l_word = l_word_neg, type = "-")
seq <- seqinr::read.fasta(file)
if (n_ana > 1) stop("Analysis for multiple files is not implemented yet")
raw_seq <- seq[[1]]
long <- length(raw_seq)
beg <- max(l_word_pos, l_word_neg)
# compute p_initial and transition matrix for markov
pos_init <- neg_init <- log(0.5)
l_c <- 1 / l_c
l_nc <- 1 / l_nc
trans_mod <- log(matrix(c(
1 - l_c, l_nc,
l_c, 1 - l_nc
),
ncol = 2, nrow = 2
))
colnames(trans_mod) <- rownames(trans_mod) <- c("c", "nc")
# initialisation
ncol <- 7
proba <- matrix(rep(NA, long * ncol), ncol = ncol)
colnames(proba) <- c("M+", "M-", "model", "length", "rep_length", "begin", "end")
# time explode if it is not a matrix anymore !!!
# proba <- as.data.frame(proba)
# old version is v2 takes too long
# v1 = function(){
# trans_pos[which(names(trans_pos)==paste(raw_seq[(beg-l_word_pos+1):beg],collapse = ""))]
# }
# v2 = function(){
# min(count(raw_seq[(beg-l_word_pos+1):beg], l_word_pos) * trans_pos)
# }
# system.time(v1())
# system.time(v2())
# compute first base and initiate Viterbi
proba[beg, "M+"] <- trans_pos[which(names(trans_pos) == paste(raw_seq[(beg - l_word_pos + 1):beg], collapse = ""))] + pos_init
proba[beg, "M-"] <- trans_neg[which(names(trans_neg) == paste(raw_seq[(beg - l_word_neg + 1):beg], collapse = ""))] + neg_init
if (proba[beg, "M+"] > proba[beg, "M-"]) {
proba[beg, "model"] <- 1
} else {
proba[beg, "model"] <- 2
}
proba[beg, c("length", "rep_length")] <- 1
tmp <- proba[beg, c(6, 7)] <- beg
proba[1:beg - 1, "rep_length"] <- beg - 1
proba[1:beg - 1, "model"] <- 3
proba[1, "begin"] <- 1
proba[beg - 1, c(4, 7)] <- beg - 1
beg <- beg + 1
cat("\n ============ Viterbi is running ============ \n\n")
pb <- utils::txtProgressBar(min = beg, max = long, style = 3)
for (i in beg:long) {
utils::setTxtProgressBar(pb, i)
# proba d'avoir la base sous M
pM <- trans_pos[which(names(trans_pos) == paste(raw_seq[(i - l_word_pos + 1):i], collapse = ""))] + max(
proba[i - 1, "M+"] + trans_mod[1, 1],
proba[i - 1, "M-"] + trans_mod[2, 1]
)
# proba d'avoir la base sous m
pm <- trans_neg[which(names(trans_neg) == paste(raw_seq[(i - l_word_neg + 1):i], collapse = ""))] + max(
proba[i - 1, "M-"] + trans_mod[2, 2],
proba[i - 1, "M+"] + trans_mod[1, 2]
)
proba[i, "M+"] <- pM
proba[i, "M-"] <- pm
if (proba[i, "M+"] > proba[i, 2]) {
proba[i, "model"] <- 1
} else {
proba[i, "model"] <- 2
}
# length information
if (proba[i, "model"] == proba[i - 1, "model"]) {
proba[i, "length"] <- proba[i - 1, "length"] + 1 # increase part length
proba[i - 1, c(4, 7)] <- NA # erase length in previous ligne
} else {
proba[i, "length"] <- 1 # initiate new part length
proba[i - 1, "end"] <- i - 1 # put end value of precedent part
proba[c(tmp:(i - 1)), "rep_length"] <- proba[i - 1, "length"] # rep value of length for precedent part
proba[i, "begin"] <- tmp <- i # put begin value of the actual part
}
}
close(pb)
# closing table
proba[i, "end"] <- i # put end value of precedent part
proba[c(tmp:(i)), "rep_length"] <- proba[i, "length"] # rep value of length for precedent part
# add a column for the line number
proba <- cbind(c(1:dim(proba)[1]), proba)
colnames(proba)[1] <- "n"
return(proba)
}
#' smoothing
#'
#' Use the export table of viterbi function and apply two algorithms to smooth the data by two different variables
#'
#' @param seq export table of viterbi function
#' @param l_word_pos a value for lengths of words for the model. Equal to the "order of the model + 1"
#' @param l_word_neg a value fof lengths of words for the model. Equal to the "order of the model + 1"
#' @param smooth_win minimal region length for a region to be kept under model + or -
#' @param reject_win minimal region length for a region ambiguous to be kept under model ambiguous
#'
#' @author Jaunatre Maxime <maxime.jaunatre@etu.univ-grenoble-alpes.fr>
#'
#' @export
smoothing <- function(seq,
l_word_pos = 5,
l_word_neg = 4,
smooth_win = 10,
reject_win = 1) {
beg <- max(l_word_pos, l_word_neg)
# finding ambiguous regions which are shorter than a certain windows
cat(" ============ Smoothing ============ \n")
seq <- cbind(seq, seq[, 4])
colnames(seq)[9] <- c("smoothed")
seq[which(seq[, "rep_length"] <= smooth_win), "smoothed"] <- 3
# old version is v1 takes too long
# v1 = function(){
# cat(" ============ Smoothing boucle ============ \n")
# pb <- utils::txtProgressBar(min = 1, max = max(seq[, 1]), style = 3)
# for (i in 1:dim(seq)[1]) {
# utils::setTxtProgressBar(pb, i)
# if (seq[i, 6] <= smooth_win) {
# seq[i, "smoothed"] <- 3
# }
# }
# close(pb)
# }
# v2 = function(){
# seq[which(seq[, 6] <= smooth_win), "smoothed"] <- 3}
# system.time(v1())
# system.time(v2())
# unified ambiguous regions
seq <- cbind(seq, seq[, c(5:8)])
colnames(seq)[10:13] <- paste("S_", colnames(seq[, c(10:13)]), sep = "")
seq[beg, "S_length"] <- 1
tmp <- seq[beg, c("S_begin", "S_end")] <- beg
seq[-c(1:beg), c(10:13)] <- NA
beg <- beg + 1
cat("\n ============ Smoothing length ============ \n")
pb <- utils::txtProgressBar(min = beg - 1, max = dim(seq)[1], style = 3)
for (i in beg:dim(seq)[1]) {
utils::setTxtProgressBar(pb, i)
if (seq[i, "smoothed"] == seq[i - 1, "smoothed"]) {
seq[i, "S_length"] <- seq[i - 1, "S_length"] + 1 # increase part length
seq[i - 1, c("S_length", "S_end")] <- NA # erase length in previous ligne
} else {
seq[i, "S_length"] <- 1 # initiate new part length
seq[i - 1, "S_end"] <- i - 1 # put end value of precedent part
seq[c(tmp:(i - 1)), "S_rep_length"] <- seq[i - 1, "S_length"] # rep value of length for precedent part
seq[i, "S_begin"] <- tmp <- i # put begin value of the actual part
}
}
close(pb)
# closing table
seq[i, 13] <- i # put end value of precedent part
seq[c(tmp:(i)), 11] <- seq[i, 10] # rep value of length for precedent part
# to reject some region and put arbitrary models on them
if(reject_win > 1){
colnames(seq)[10:13] <- paste("R_", colnames(seq[, c(10:13)]), sep = "")
head(seq)
cat(" ============ Rejecting ============ \n")
# finding regions of length < reject_win between tho regions of same model. Changing the model to surrounding
solo_l <-seq[which(seq[,"R_S_length"] %in% unique(seq[, "R_S_rep_length"])),c("smoothed","R_S_rep_length")]
for(i in 2:(dim(solo_l)[1]-1)){
if(solo_l[i-1,1]==solo_l[i+1,1] && solo_l[i,2] < reject_win && solo_l[i,1] == 3) {solo_l[i,1] <- solo_l[i-1,1]}
}
seq[,"smoothed"] <- rep(solo_l[,1],solo_l[,2])
beg <- beg - 1
seq[beg, "R_S_length"] <- 1
tmp <- seq[beg, c("R_S_begin", "R_S_end")] <- beg
seq[-c(1:beg), c(10:13)] <- NA
beg <- beg + 1
seq[-c(1:beg), c(10:13)] <- NA
cat("\n ============ Smoothing length after reject ============ \n")
pb <- utils::txtProgressBar(min = beg - 1, max = dim(seq)[1], style = 3)
for (i in beg:dim(seq)[1]) {
utils::setTxtProgressBar(pb, i)
if (seq[i, "smoothed"] == seq[i - 1, "smoothed"]) {
seq[i, "R_S_length"] <- seq[i - 1, "R_S_length"] + 1 # increase part length
seq[i - 1, c("R_S_length", "R_S_end")] <- NA # erase length in previous ligne
} else {
seq[i, "R_S_length"] <- 1 # initiate new part length
seq[i - 1, "R_S_end"] <- i - 1 # put end value of precedent part
seq[c(tmp:(i - 1)), "R_S_rep_length"] <- seq[i - 1, "R_S_length"] # rep value of length for precedent part
seq[i, "R_S_begin"] <- tmp <- i # put begin value of the actual part
}
}
close(pb)
# closing table
seq[i, 13] <- i # put end value of precedent part
seq[c(tmp:(i)), 11] <- seq[i, 10] # rep value of length for precedent part
}
return(seq)
}
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