Nothing
R/changePostCutoff.R
In chromstaR: Combinatorial and Differential Chromatin State Analysis for ChIP-Seq Data
Defines functions
changeFDR
changePostCutoff.univariate
changePostCutoff.multivariate
changePostCutoff
changeMaxPostCutoff.univariate
changeMaxPostCutoff.multivariate
changeMaxPostCutoff
Documented in
changeFDR
changeMaxPostCutoff
changePostCutoff
#' Adjust sensitivity of peak detection
#'
#' Adjusts the peak calls of a \code{\link{uniHMM}}, \code{\link{multiHMM}} or \code{\link{combinedMultiHMM}} object with a cutoff on the maximum-posterior within each peak. Higher values of \code{maxPost.cutoff} mean less sensitive and more precise peak calls. Remaining peaks are kept intact, as opposed to function \code{\link{changePostCutoff}}, where broad peaks are fragmented. This function was formerly called 'changeFDR' and is still available for backwards compatibiltiy.
#'
#' Each peak has a maximum-posterior (maxPostInPeak, between 0 and 1) associated. The sensitivity is adjusted with a simple cutoff on maxPostInPeak, e.g. for \code{maxPost.cutoff = 0.99} only peaks with \code{maxPostInPeak >= 0.99} will be selected.
#'
#' @author Aaron Taudt
#' @param model A \code{\link{uniHMM}} or \code{\link{multiHMM}} object with posteriors.
#' @param maxPost.cutoff A vector of values between 0 and 1 for each column in \code{model$bins$posteriors}. If only one value is given, it will be reused for all columns. Values close to 1 will yield more stringent peak calls with lower false positive but higher false negative rate (i.e. more precise but less sensitive).
#' @param invert Select peaks below (\code{FALSE}) or above (\code{TRUE}) the given \code{maxPost.cutoff}. This is useful to select low confidence peaks.
#' @return The input object is returned with adjusted peak calls.
#' @export
#' @seealso \code{\link{changePostCutoff}}
#' @examples
#'## Get an example uniHMM ##
#'file <- system.file("data","H3K27me3-BN-rep1.RData", package="chromstaR")
#'model <- get(load(file))
#'## Compare fits with different fdrs
#'plotHistogram(model) + ylim(0,0.25) + ylim(0,0.3)
#'plotHistogram(changeMaxPostCutoff(model, maxPost.cutoff=0.99)) + ylim(0,0.3)
#'plotHistogram(changeMaxPostCutoff(model, maxPost.cutoff=1-1e-12)) + ylim(0,0.3)
#'
#'## Get an example multiHMM ##
#'file <- system.file("data","multivariate_mode-combinatorial_condition-SHR.RData",
#' package="chromstaR")
#'model <- get(load(file))
#'genomicFrequencies(model)
#'model.new <- changeMaxPostCutoff(model, maxPost.cutoff=0.9999, invert=FALSE)
#'genomicFrequencies(model.new)
#'
#'## Get an example combinedMultiHMM ##
#'file <- system.file("data","combined_mode-differential.RData",
#' package="chromstaR")
#'model <- get(load(file))
#'genomicFrequencies(model)
#'model.new <- changeMaxPostCutoff(model, maxPost.cutoff=0.9999, invert=FALSE)
#'genomicFrequencies(model.new)
#'
changeMaxPostCutoff <- function(model, maxPost.cutoff=0.99, invert=FALSE) {
if (!is.numeric(maxPost.cutoff)) {
warning("'maxPost.cutoff' is not numeric. Nothing done.")
return(model)
}
if (is(model, class.univariate.hmm)) {
model.new <- changeMaxPostCutoff.univariate(model=model, maxPost.cutoff=maxPost.cutoff, invert=invert)
} else if (is(model, class.multivariate.hmm) | is(model, class.combined.multivariate.hmm)) {
model.new <- changeMaxPostCutoff.multivariate(model=model, maxPost.cutoff=maxPost.cutoff, invert=invert)
}
return(model.new)
}
changeMaxPostCutoff.multivariate <- function(model, maxPost.cutoff, invert=FALSE) {
## Make maxPost.cutoff vector
if (is.null(model$bins$posteriors)) stop("Cannot recalculate states because posteriors are missing.")
numcol <- ncol(model$bins$posteriors)
if (length(maxPost.cutoff) == 1) {
maxPost.cutoff <- rep(maxPost.cutoff, numcol)
}
if (length(maxPost.cutoff) != numcol) {
stop("Need ", numcol, " values in 'maxPost.cutoff' but only ", length(maxPost.cutoff), " are provided.")
}
for (maxPost.cutoff.i in maxPost.cutoff) {
if (maxPost.cutoff.i < 0 | maxPost.cutoff.i > 1) {
stop("Values for 'maxPost.cutoff' need to be inside the interval [0,1].")
}
}
names(maxPost.cutoff) <- colnames(model$bins$posteriors)
# Check if replicates have the same maxPost.cutoff value
reps <- sub('-rep.*', '', model$info$ID)
if (any(sapply(split(maxPost.cutoff, reps), function(x) { Reduce('&', x==x[1]) }) == FALSE)) {
stop("Replicates must have the same maxPost.cutoff value.")
}
## maxPost.cutoff threshold
threshold <- maxPost.cutoff
### Multivariate HMM ###
if (is(model, class.multivariate.hmm)) {
## Calculate states
ptm <- startTimedMessage("Calculating states from maximum-posterior in each peak ...")
if (is.null(model$bins$maxPostInPeak)) {
p <- getMaxPostInPeaks(model$bins$state, model$bins$posteriors)
} else {
p <- model$bins$maxPostInPeak
}
p.thresholded <- matrix(FALSE, ncol=ncol(p), nrow=nrow(p))
for (icol in 1:ncol(p)) {
if (!invert) {
p.thresholded[,icol] <- p[,icol] >= threshold[icol]
} else {
p.thresholded[,icol] <- p[,icol] < threshold[icol] & p[,icol] > 0
}
}
states <- factor(bin2dec(p.thresholded), levels=levels(model$bins$state))
model$bins$state <- states
## Combinations
if (!is.null(model$bins$combination)) {
mapping <- model$mapping
model$bins$combination <- factor(mapping[as.character(model$bins$state)], levels=mapping[as.character(levels(model$bins$state))])
}
stopTimedMessage(ptm)
## Redo segmentation
model$segments <- multivariateSegmentation(model$bins, column2collapseBy='state')
## Add differential score ##
ptm <- startTimedMessage("Adding differential score ...")
model$segments$differential.score <- differentialScoreSum(model$segments$maxPostInPeak, model$infos)
stopTimedMessage(ptm)
## Maximum posterior in peaks ##
ptm <- startTimedMessage("Getting maximum posterior in peaks ...")
ind <- findOverlaps(model$bins, model$segments)
model$bins$maxPostInPeak <- model$segments$maxPostInPeak[subjectHits(ind), , drop=FALSE]
model$bins$differential.score <- model$segments$differential.score[subjectHits(ind)]
stopTimedMessage(ptm)
## Redo peaks
ptm <- startTimedMessage("Recalculating peaks ...")
model$peaks <- list()
for (i1 in 1:ncol(model$segments$maxPostInPeak)) {
mask <- model$segments$maxPostInPeak[,i1] > 0
peaks <- model$segments[mask]
mcols(peaks) <- NULL
peaks$maxPostInPeak <- model$segments$maxPostInPeak[mask,i1]
model$peaks[[i1]] <- peaks
}
names(model$peaks) <- colnames(model$segments$maxPostInPeak)
stopTimedMessage(ptm)
} else if (is(model, class.combined.multivariate.hmm)) {
ptm <- startTimedMessage("Calculating states from maximum-posterior in each peak ...")
if (is.null(model$bins$maxPostInPeak)) {
p <- getMaxPostInPeaks(model$bins$state, model$bins$posteriors)
} else {
p <- model$bins$maxPostInPeak
}
p.thresholded <- matrix(FALSE, ncol=ncol(p), nrow=nrow(p))
for (icol in 1:ncol(p)) {
if (!invert) {
p.thresholded[,icol] <- p[,icol] >= threshold[icol]
} else {
p.thresholded[,icol] <- p[,icol] < threshold[icol] & p[,icol] > 0
}
}
decstates <- bin2dec(p.thresholded)
binary.matrix <- p.thresholded[!duplicated(decstates),]
mapping.df <- stateBrewer(model$info[,setdiff(names(model$info), 'ID')], mode='full')
mapping <- mapping.df$combination
names(mapping) <- mapping.df$state
states <- factor(decstates, levels=mapping.df$state)
stopTimedMessage(ptm)
## Make fake multiHMM to do the segmentation with "combineMultivariates"
multiHMM <- list()
class(multiHMM) <- class.multivariate.hmm
multiHMM$info <- model$info
multiHMM$bins <- model$bins
multiHMM$bins$combination <- mapping[as.character(states)]
multiHMM$bins$state <- factor(states)
multiHMM$bins$posteriors <- model$bins$posteriors
## Redo maxPostInPeak
ptm <- startTimedMessage("Re-estimating maximum posterior in peaks ...")
multiHMM$bins$maxPostInPeak <- getMaxPostInPeaks(multiHMM$bins$state, multiHMM$bins$posteriors)
stopTimedMessage(ptm)
multiHMM$mapping <- mapping
multiHMM$peaks <- model$peaks
model <- combineMultivariates(list(multiHMM), mode='full')
## Redo peaks
ptm <- startTimedMessage("Recalculating peaks ...")
model$peaks <- list()
for (i1 in 1:ncol(model$segments$maxPostInPeak)) {
mask <- model$segments$maxPostInPeak[,i1] > 0
peaks <- model$segments[mask]
mcols(peaks) <- NULL
peaks$maxPostInPeak <- model$segments$maxPostInPeak[mask,i1]
model$peaks[[i1]] <- peaks
}
names(model$peaks) <- colnames(model$segments$maxPostInPeak)
stopTimedMessage(ptm)
} else {
stop("Supply either a uniHMM, multiHMM or combinedMultiHMM object.")
}
## Return model
model$maxPost.cutoff <- maxPost.cutoff
return(model)
}
changeMaxPostCutoff.univariate <- function(model, maxPost.cutoff, invert=FALSE) {
maxPost.cutoff <- suppressWarnings( as.numeric(maxPost.cutoff) )
if (!is.numeric(maxPost.cutoff) | is.na(maxPost.cutoff)) {
warning("Not changing false discovery rate because given 'maxPost.cutoff' is not numeric.")
return(model)
} else if (maxPost.cutoff < 0 | maxPost.cutoff > 1) {
warning("maxPost.cutoff has to be inside the interval [0,1]. Nothing done.")
return(model)
}
## maxPost.cutoff threshold
threshold <- maxPost.cutoff
if (is.null(model$bins$posterior.modified)) stop("Cannot recalculate states because column 'posterior.modified' is missing.")
## Calculate states
ptm <- startTimedMessage("Calculating states from maximum-posterior in each peak ...")
if (is.null(model$bins$maxPostInPeak)) {
model$bins$maxPostInPeak <- getMaxPostInPeaks.univariate(model$bins$state, model$bins$posterior.modified)
}
states <- model$bins$state
states[model$bins$state == 'modified'] <- 'unmodified'
if (!invert) {
states[ model$bins$maxPostInPeak >= threshold ] <- 'modified'
} else {
states[ model$bins$maxPostInPeak < threshold & model$bins$maxPostInPeak > 0 ] <- 'modified'
}
model$bins$state <- states
model$bins$maxPostInPeak <- NULL
stopTimedMessage(ptm)
## Redo maxPostInPeak
ptm <- startTimedMessage("Re-estimating maximum posterior in peaks ...")
model$bins$maxPostInPeak <- getMaxPostInPeaks.univariate(model$bins$state, model$bins$posterior.modified)
stopTimedMessage(ptm)
## Redo segmentation
ptm <- startTimedMessage("Making segmentation ...")
gr <- model$bins
df <- as.data.frame(gr)
red.df <- suppressMessages(collapseBins(df, column2collapseBy='state', columns2drop=c('width',grep('posteriors', names(df), value=TRUE), 'counts', 'counts.rpkm', 'posterior.modified')))
model$segments <- methods::as(red.df, 'GRanges')
seqlengths(model$segments) <- seqlengths(model$bins)[seqlevels(model$segments)]
## Redo peaks
model$peaks <- model$segments[model$segments$state == 'modified']
model$peaks$state <- NULL
model$segments <- NULL
## Redo weights
model$weights <- table(model$bins$state) / length(model$bins)
stopTimedMessage(ptm)
## Return model
model$maxPost.cutoff <- maxPost.cutoff
return(model)
}
#' Change the posterior cutoff of a Hidden Markov Model
#'
#' Adjusts the peak calls of a \code{\link{uniHMM}}, \code{\link{multiHMM}} or \code{\link{combinedMultiHMM}} object with the given posterior cutoff.
#'
#' Posterior probabilities are between 0 and 1. Peaks are called if the posteriors for a state (univariate) or sample (multivariate) are >= \code{post.cutoff}.
#'
#' @author Aaron Taudt
#' @param model A \code{\link{uniHMM}} or \code{\link{multiHMM}} object with posteriors.
#' @param post.cutoff A vector of posterior cutoff values between 0 and 1 the same length as \code{ncol(model$bins$posteriors)}. If only one value is given, it will be reused for all columns. Values close to 1 will yield more stringent peak calls with lower false positive but higher false negative rate.
#' @return The input object is returned with adjusted peak calls.
#' @export
#' @seealso \code{\link{changeMaxPostCutoff}}
#' @examples
#'## Get an example BAM file with ChIP-seq reads
#'file <- system.file("extdata", "euratrans",
#' "lv-H3K27me3-BN-male-bio2-tech1.bam",
#' package="chromstaRData")
#'## Bin the BED file into bin size 1000bp
#'data(rn4_chrominfo)
#'data(experiment_table)
#'binned <- binReads(file, experiment.table=experiment_table,
#' assembly=rn4_chrominfo, binsizes=1000,
#' stepsizes=500, chromosomes='chr12')
#'plotHistogram(binned)
#'## Fit HMM
#'model <- callPeaksUnivariate(binned, keep.posteriors=TRUE, verbosity=0)
#'## Compare fits with different post.cutoffs
#'plotHistogram(changePostCutoff(model, post.cutoff=0.01)) + ylim(0,0.25)
#'plotHistogram(model) + ylim(0,0.25)
#'plotHistogram(changePostCutoff(model, post.cutoff=0.99)) + ylim(0,0.25)
#'
#'## Get an example multiHMM ##
#'file <- system.file("data","multivariate_mode-combinatorial_condition-SHR.RData",
#' package="chromstaR")
#'model <- get(load(file))
#'genomicFrequencies(model)
#'model.new <- changePostCutoff(model, post.cutoff=0.9999)
#'genomicFrequencies(model.new)
#'
#'## Get an example combinedMultiHMM ##
#'file <- system.file("data","combined_mode-differential.RData",
#' package="chromstaR")
#'model <- get(load(file))
#'genomicFrequencies(model)
#'model.new <- changePostCutoff(model, post.cutoff=0.9999)
#'genomicFrequencies(model.new)
#'
changePostCutoff <- function(model, post.cutoff=0.5) {
if (!is.numeric(post.cutoff)) {
warning("'post.cutoff' is not numeric. Nothing done.")
return(model)
}
if (is(model, class.univariate.hmm)) {
model.new <- changePostCutoff.univariate(model=model, post.cutoff=post.cutoff)
} else if (is(model, class.multivariate.hmm) | is(model, class.combined.multivariate.hmm)) {
model.new <- changePostCutoff.multivariate(model=model, post.cutoff=post.cutoff)
}
return(model.new)
}
changePostCutoff.multivariate <- function(model, post.cutoff) {
## Make post.cutoff vector
if (is.null(model$bins$posteriors)) stop("Cannot recalculate states because posteriors are missing.")
numcol <- ncol(model$bins$posteriors)
if (length(post.cutoff) == 1) {
post.cutoff <- rep(post.cutoff, numcol)
}
if (length(post.cutoff) != numcol) {
stop("Need ", numcol, " values in 'post.cutoff' but only ", length(post.cutoff), " are provided.")
}
for (post.cutoff.i in post.cutoff) {
if (post.cutoff.i < 0 | post.cutoff.i > 1) {
stop("Values for 'post.cutoff' need to be inside the interval [0,1].")
}
}
names(post.cutoff) <- colnames(model$bins$posteriors)
# Check if replicates have the same post.cutoff value
reps <- sub('-rep.*', '', model$info$ID)
if (any(sapply(split(post.cutoff, reps), function(x) { Reduce('&', x==x[1]) }) == FALSE)) {
stop("Replicates must have the same post.cutoff value.")
}
## post.cutoff threshold
threshold <- post.cutoff
### Multivariate HMM ###
if (is(model, class.multivariate.hmm)) {
## Calculate states
ptm <- startTimedMessage("Calculating states from posteriors ...")
post <- model$bins$posteriors
post.thresholded <- matrix(FALSE, ncol=ncol(post), nrow=nrow(post))
for (icol in 1:ncol(post)) {
post.thresholded[,icol] <- post[,icol] >= threshold[icol]
}
states <- factor(bin2dec(post.thresholded), levels=levels(model$bins$state))
model$bins$state <- states
## Combinations
if (!is.null(model$bins$combination)) {
mapping <- model$mapping
model$bins$combination <- factor(mapping[as.character(model$bins$state)], levels=mapping[as.character(levels(model$bins$state))])
}
stopTimedMessage(ptm)
## Redo segmentation
model$segments <- multivariateSegmentation(model$bins, column2collapseBy='state')
## Add differential score ##
ptm <- startTimedMessage("Adding differential score ...")
model$segments$differential.score <- differentialScoreSum(model$segments$maxPostInPeak, model$infos)
stopTimedMessage(ptm)
## Maximum posterior in peaks ##
ptm <- startTimedMessage("Getting maximum posterior in peaks ...")
ind <- findOverlaps(model$bins, model$segments)
model$bins$maxPostInPeak <- model$segments$maxPostInPeak[subjectHits(ind), , drop=FALSE]
model$bins$differential.score <- model$segments$differential.score[subjectHits(ind)]
stopTimedMessage(ptm)
## Redo peaks
ptm <- startTimedMessage("Recalculating peaks ...")
model$peaks <- list()
for (i1 in 1:ncol(model$segments$maxPostInPeak)) {
mask <- model$segments$maxPostInPeak[,i1] > 0
peaks <- model$segments[mask]
mcols(peaks) <- NULL
peaks$maxPostInPeak <- model$segments$maxPostInPeak[mask,i1]
model$peaks[[i1]] <- peaks
}
names(model$peaks) <- colnames(model$segments$maxPostInPeak)
stopTimedMessage(ptm)
} else if (is(model, class.combined.multivariate.hmm)) {
ptm <- startTimedMessage("Calculating states from posteriors ...")
post <- model$bins$posteriors
post.thresholded <- matrix(FALSE, ncol=ncol(post), nrow=nrow(post))
for (icol in 1:ncol(post)) {
post.thresholded[,icol] <- post[,icol] >= threshold[icol]
}
decstates <- bin2dec(post.thresholded)
binary.matrix <- post.thresholded[!duplicated(decstates),]
mapping.df <- stateBrewer(model$info[,setdiff(names(model$info), 'ID')], mode='full', binary.matrix = binary.matrix)
mapping <- mapping.df$combination
names(mapping) <- mapping.df$state
states <- factor(decstates, levels=mapping.df$state)
stopTimedMessage(ptm)
## Make fake multiHMM
multiHMM <- list()
class(multiHMM) <- class.multivariate.hmm
multiHMM$info <- model$info
multiHMM$bins <- model$bins
multiHMM$bins$combination <- mapping[as.character(states)]
multiHMM$bins$state <- factor(states)
multiHMM$bins$posteriors <- post
## Redo maxPostInPeak
ptm <- startTimedMessage("Re-estimating maximum posterior in peaks ...")
multiHMM$bins$maxPostInPeak <- getMaxPostInPeaks(multiHMM$bins$state, multiHMM$bins$posteriors)
stopTimedMessage(ptm)
multiHMM$mapping <- mapping
multiHMM$peaks <- model$peaks
model <- combineMultivariates(list(multiHMM), mode='full')
## Redo peaks
ptm <- startTimedMessage("Recalculating peaks ...")
model$peaks <- list()
for (i1 in 1:ncol(model$segments$maxPostInPeak)) {
mask <- model$segments$maxPostInPeak[,i1] > 0
peaks <- model$segments[mask]
mcols(peaks) <- NULL
peaks$maxPostInPeak <- model$segments$maxPostInPeak[mask,i1]
model$peaks[[i1]] <- peaks
}
names(model$peaks) <- colnames(model$segments$maxPostInPeak)
stopTimedMessage(ptm)
} else {
stop("Supply either a uniHMM, multiHMM or combinedMultiHMM object.")
}
## Return model
model$post.cutoff <- threshold
return(model)
}
changePostCutoff.univariate <- function(model, post.cutoff) {
post.cutoff <- suppressWarnings( as.numeric(post.cutoff) )
if (!is.numeric(post.cutoff) | is.na(post.cutoff)) {
warning("Not changing posterior cutoff because given 'post.cutoff' is not numeric.")
return(model)
} else if (post.cutoff < 0 | post.cutoff > 1) {
warning("post.cutoff has to be inside the interval [0,1]. Nothing done.")
return(model)
}
## post.cutoff threshold
threshold <- post.cutoff
model$post.cutoff <- post.cutoff
if (is.null(model$bins$posteriors) & is.null(model$bins$posterior.modified)) stop("Cannot recalculate states because posteriors are missing. Run 'callPeaksUnivariate' again with option 'keep.posteriors' set to TRUE.")
## Calculate states
ptm <- startTimedMessage("Calculating states from posteriors ...")
if (is.null(model$bins$posteriors)) {
warning("Using column 'posterior.modified' to recalculate states, there will be no state 'zero-inflation' in the output. Run 'callPeaksUnivariate' again with option 'keep.posteriors' set to TRUE to also obtain 'zero-inflation' states.")
states <- rep(2,length(model$bins))
states[ model$bins$posterior.modified>=threshold ] <- 3
} else {
states <- rep(NA,length(model$bins))
states[ model$bins$posteriors[,3]<threshold & model$bins$posteriors[,2]<=model$bins$posteriors[,1] ] <- 1
states[ model$bins$posteriors[,3]<threshold & model$bins$posteriors[,2]>model$bins$posteriors[,1] ] <- 2
states[ model$bins$posteriors[,3]>=threshold ] <- 3
}
states <- state.labels[states]
model$bins$state <- states
stopTimedMessage(ptm)
## Redo maxPostInPeak
ptm <- startTimedMessage("Re-estimating maximum posterior in peaks ...")
model$bins$maxPostInPeak <- getMaxPostInPeaks.univariate(model$bins$state, model$bins$posterior.modified)
stopTimedMessage(ptm)
## Redo segmentation
ptm <- startTimedMessage("Making segmentation ...")
gr <- model$bins
df <- as.data.frame(gr)
red.df <- suppressMessages(collapseBins(df, column2collapseBy='state', columns2drop=c('width', 'posterior.modified', grep('posteriors', names(df), value=TRUE), 'counts', 'counts.rpkm', 'posterior.modified')))
segments <- methods::as(red.df, 'GRanges')
model$peaks <- segments[segments$state == 'modified']
model$peaks$state <- NULL
seqlengths(model$peaks) <- seqlengths(model$bins)[seqlevels(model$peaks)]
stopTimedMessage(ptm)
## Return model
return(model)
}
#' @describeIn changeMaxPostCutoff This function was renamed to 'changeMaxPostCutoff' in chromstaR 1.5.1 but it still available for backwards compatibility.
#' @export
#' @param fdr Same as \code{1-maxPost.cutoff}.
changeFDR <- function(model, fdr=0.01, invert=FALSE) {
warning("Usage of 'changeFDR' is discouraged since chromstaR 1.5.1. Please use 'changeMaxPostCutoff' instead.")
return(changeMaxPostCutoff(model=model, maxPost.cutoff=1-fdr, invert=invert))
}
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Defines functions changeFDR changePostCutoff.univariate changePostCutoff.multivariate changePostCutoff changeMaxPostCutoff.univariate changeMaxPostCutoff.multivariate changeMaxPostCutoff
Documented in changeFDR changeMaxPostCutoff changePostCutoff
#' Adjust sensitivity of peak detection
#'
#' Adjusts the peak calls of a \code{\link{uniHMM}}, \code{\link{multiHMM}} or \code{\link{combinedMultiHMM}} object with a cutoff on the maximum-posterior within each peak. Higher values of \code{maxPost.cutoff} mean less sensitive and more precise peak calls. Remaining peaks are kept intact, as opposed to function \code{\link{changePostCutoff}}, where broad peaks are fragmented. This function was formerly called 'changeFDR' and is still available for backwards compatibiltiy.
#'
#' Each peak has a maximum-posterior (maxPostInPeak, between 0 and 1) associated. The sensitivity is adjusted with a simple cutoff on maxPostInPeak, e.g. for \code{maxPost.cutoff = 0.99} only peaks with \code{maxPostInPeak >= 0.99} will be selected.
#'
#' @author Aaron Taudt
#' @param model A \code{\link{uniHMM}} or \code{\link{multiHMM}} object with posteriors.
#' @param maxPost.cutoff A vector of values between 0 and 1 for each column in \code{model$bins$posteriors}. If only one value is given, it will be reused for all columns. Values close to 1 will yield more stringent peak calls with lower false positive but higher false negative rate (i.e. more precise but less sensitive).
#' @param invert Select peaks below (\code{FALSE}) or above (\code{TRUE}) the given \code{maxPost.cutoff}. This is useful to select low confidence peaks.
#' @return The input object is returned with adjusted peak calls.
#' @export
#' @seealso \code{\link{changePostCutoff}}
#' @examples
#'## Get an example uniHMM ##
#'file <- system.file("data","H3K27me3-BN-rep1.RData", package="chromstaR")
#'model <- get(load(file))
#'## Compare fits with different fdrs
#'plotHistogram(model) + ylim(0,0.25) + ylim(0,0.3)
#'plotHistogram(changeMaxPostCutoff(model, maxPost.cutoff=0.99)) + ylim(0,0.3)
#'plotHistogram(changeMaxPostCutoff(model, maxPost.cutoff=1-1e-12)) + ylim(0,0.3)
#'
#'## Get an example multiHMM ##
#'file <- system.file("data","multivariate_mode-combinatorial_condition-SHR.RData",
#' package="chromstaR")
#'model <- get(load(file))
#'genomicFrequencies(model)
#'model.new <- changeMaxPostCutoff(model, maxPost.cutoff=0.9999, invert=FALSE)
#'genomicFrequencies(model.new)
#'
#'## Get an example combinedMultiHMM ##
#'file <- system.file("data","combined_mode-differential.RData",
#' package="chromstaR")
#'model <- get(load(file))
#'genomicFrequencies(model)
#'model.new <- changeMaxPostCutoff(model, maxPost.cutoff=0.9999, invert=FALSE)
#'genomicFrequencies(model.new)
#'
changeMaxPostCutoff <- function(model, maxPost.cutoff=0.99, invert=FALSE) {
if (!is.numeric(maxPost.cutoff)) {
warning("'maxPost.cutoff' is not numeric. Nothing done.")
return(model)
}
if (is(model, class.univariate.hmm)) {
model.new <- changeMaxPostCutoff.univariate(model=model, maxPost.cutoff=maxPost.cutoff, invert=invert)
} else if (is(model, class.multivariate.hmm) | is(model, class.combined.multivariate.hmm)) {
model.new <- changeMaxPostCutoff.multivariate(model=model, maxPost.cutoff=maxPost.cutoff, invert=invert)
}
return(model.new)
}
changeMaxPostCutoff.multivariate <- function(model, maxPost.cutoff, invert=FALSE) {
## Make maxPost.cutoff vector
if (is.null(model$bins$posteriors)) stop("Cannot recalculate states because posteriors are missing.")
numcol <- ncol(model$bins$posteriors)
if (length(maxPost.cutoff) == 1) {
maxPost.cutoff <- rep(maxPost.cutoff, numcol)
}
if (length(maxPost.cutoff) != numcol) {
stop("Need ", numcol, " values in 'maxPost.cutoff' but only ", length(maxPost.cutoff), " are provided.")
}
for (maxPost.cutoff.i in maxPost.cutoff) {
if (maxPost.cutoff.i < 0 | maxPost.cutoff.i > 1) {
stop("Values for 'maxPost.cutoff' need to be inside the interval [0,1].")
}
}
names(maxPost.cutoff) <- colnames(model$bins$posteriors)
# Check if replicates have the same maxPost.cutoff value
reps <- sub('-rep.*', '', model$info$ID)
if (any(sapply(split(maxPost.cutoff, reps), function(x) { Reduce('&', x==x[1]) }) == FALSE)) {
stop("Replicates must have the same maxPost.cutoff value.")
}
## maxPost.cutoff threshold
threshold <- maxPost.cutoff
### Multivariate HMM ###
if (is(model, class.multivariate.hmm)) {
## Calculate states
ptm <- startTimedMessage("Calculating states from maximum-posterior in each peak ...")
if (is.null(model$bins$maxPostInPeak)) {
p <- getMaxPostInPeaks(model$bins$state, model$bins$posteriors)
} else {
p <- model$bins$maxPostInPeak
}
p.thresholded <- matrix(FALSE, ncol=ncol(p), nrow=nrow(p))
for (icol in 1:ncol(p)) {
if (!invert) {
p.thresholded[,icol] <- p[,icol] >= threshold[icol]
} else {
p.thresholded[,icol] <- p[,icol] < threshold[icol] & p[,icol] > 0
}
}
states <- factor(bin2dec(p.thresholded), levels=levels(model$bins$state))
model$bins$state <- states
## Combinations
if (!is.null(model$bins$combination)) {
mapping <- model$mapping
model$bins$combination <- factor(mapping[as.character(model$bins$state)], levels=mapping[as.character(levels(model$bins$state))])
}
stopTimedMessage(ptm)
## Redo segmentation
model$segments <- multivariateSegmentation(model$bins, column2collapseBy='state')
## Add differential score ##
ptm <- startTimedMessage("Adding differential score ...")
model$segments$differential.score <- differentialScoreSum(model$segments$maxPostInPeak, model$infos)
stopTimedMessage(ptm)
## Maximum posterior in peaks ##
ptm <- startTimedMessage("Getting maximum posterior in peaks ...")
ind <- findOverlaps(model$bins, model$segments)
model$bins$maxPostInPeak <- model$segments$maxPostInPeak[subjectHits(ind), , drop=FALSE]
model$bins$differential.score <- model$segments$differential.score[subjectHits(ind)]
stopTimedMessage(ptm)
## Redo peaks
ptm <- startTimedMessage("Recalculating peaks ...")
model$peaks <- list()
for (i1 in 1:ncol(model$segments$maxPostInPeak)) {
mask <- model$segments$maxPostInPeak[,i1] > 0
peaks <- model$segments[mask]
mcols(peaks) <- NULL
peaks$maxPostInPeak <- model$segments$maxPostInPeak[mask,i1]
model$peaks[[i1]] <- peaks
}
names(model$peaks) <- colnames(model$segments$maxPostInPeak)
stopTimedMessage(ptm)
} else if (is(model, class.combined.multivariate.hmm)) {
ptm <- startTimedMessage("Calculating states from maximum-posterior in each peak ...")
if (is.null(model$bins$maxPostInPeak)) {
p <- getMaxPostInPeaks(model$bins$state, model$bins$posteriors)
} else {
p <- model$bins$maxPostInPeak
}
p.thresholded <- matrix(FALSE, ncol=ncol(p), nrow=nrow(p))
for (icol in 1:ncol(p)) {
if (!invert) {
p.thresholded[,icol] <- p[,icol] >= threshold[icol]
} else {
p.thresholded[,icol] <- p[,icol] < threshold[icol] & p[,icol] > 0
}
}
decstates <- bin2dec(p.thresholded)
binary.matrix <- p.thresholded[!duplicated(decstates),]
mapping.df <- stateBrewer(model$info[,setdiff(names(model$info), 'ID')], mode='full')
mapping <- mapping.df$combination
names(mapping) <- mapping.df$state
states <- factor(decstates, levels=mapping.df$state)
stopTimedMessage(ptm)
## Make fake multiHMM to do the segmentation with "combineMultivariates"
multiHMM <- list()
class(multiHMM) <- class.multivariate.hmm
multiHMM$info <- model$info
multiHMM$bins <- model$bins
multiHMM$bins$combination <- mapping[as.character(states)]
multiHMM$bins$state <- factor(states)
multiHMM$bins$posteriors <- model$bins$posteriors
## Redo maxPostInPeak
ptm <- startTimedMessage("Re-estimating maximum posterior in peaks ...")
multiHMM$bins$maxPostInPeak <- getMaxPostInPeaks(multiHMM$bins$state, multiHMM$bins$posteriors)
stopTimedMessage(ptm)
multiHMM$mapping <- mapping
multiHMM$peaks <- model$peaks
model <- combineMultivariates(list(multiHMM), mode='full')
## Redo peaks
ptm <- startTimedMessage("Recalculating peaks ...")
model$peaks <- list()
for (i1 in 1:ncol(model$segments$maxPostInPeak)) {
mask <- model$segments$maxPostInPeak[,i1] > 0
peaks <- model$segments[mask]
mcols(peaks) <- NULL
peaks$maxPostInPeak <- model$segments$maxPostInPeak[mask,i1]
model$peaks[[i1]] <- peaks
}
names(model$peaks) <- colnames(model$segments$maxPostInPeak)
stopTimedMessage(ptm)
} else {
stop("Supply either a uniHMM, multiHMM or combinedMultiHMM object.")
}
## Return model
model$maxPost.cutoff <- maxPost.cutoff
return(model)
}
changeMaxPostCutoff.univariate <- function(model, maxPost.cutoff, invert=FALSE) {
maxPost.cutoff <- suppressWarnings( as.numeric(maxPost.cutoff) )
if (!is.numeric(maxPost.cutoff) | is.na(maxPost.cutoff)) {
warning("Not changing false discovery rate because given 'maxPost.cutoff' is not numeric.")
return(model)
} else if (maxPost.cutoff < 0 | maxPost.cutoff > 1) {
warning("maxPost.cutoff has to be inside the interval [0,1]. Nothing done.")
return(model)
}
## maxPost.cutoff threshold
threshold <- maxPost.cutoff
if (is.null(model$bins$posterior.modified)) stop("Cannot recalculate states because column 'posterior.modified' is missing.")
## Calculate states
ptm <- startTimedMessage("Calculating states from maximum-posterior in each peak ...")
if (is.null(model$bins$maxPostInPeak)) {
model$bins$maxPostInPeak <- getMaxPostInPeaks.univariate(model$bins$state, model$bins$posterior.modified)
}
states <- model$bins$state
states[model$bins$state == 'modified'] <- 'unmodified'
if (!invert) {
states[ model$bins$maxPostInPeak >= threshold ] <- 'modified'
} else {
states[ model$bins$maxPostInPeak < threshold & model$bins$maxPostInPeak > 0 ] <- 'modified'
}
model$bins$state <- states
model$bins$maxPostInPeak <- NULL
stopTimedMessage(ptm)
## Redo maxPostInPeak
ptm <- startTimedMessage("Re-estimating maximum posterior in peaks ...")
model$bins$maxPostInPeak <- getMaxPostInPeaks.univariate(model$bins$state, model$bins$posterior.modified)
stopTimedMessage(ptm)
## Redo segmentation
ptm <- startTimedMessage("Making segmentation ...")
gr <- model$bins
df <- as.data.frame(gr)
red.df <- suppressMessages(collapseBins(df, column2collapseBy='state', columns2drop=c('width',grep('posteriors', names(df), value=TRUE), 'counts', 'counts.rpkm', 'posterior.modified')))
model$segments <- methods::as(red.df, 'GRanges')
seqlengths(model$segments) <- seqlengths(model$bins)[seqlevels(model$segments)]
## Redo peaks
model$peaks <- model$segments[model$segments$state == 'modified']
model$peaks$state <- NULL
model$segments <- NULL
## Redo weights
model$weights <- table(model$bins$state) / length(model$bins)
stopTimedMessage(ptm)
## Return model
model$maxPost.cutoff <- maxPost.cutoff
return(model)
}
#' Change the posterior cutoff of a Hidden Markov Model
#'
#' Adjusts the peak calls of a \code{\link{uniHMM}}, \code{\link{multiHMM}} or \code{\link{combinedMultiHMM}} object with the given posterior cutoff.
#'
#' Posterior probabilities are between 0 and 1. Peaks are called if the posteriors for a state (univariate) or sample (multivariate) are >= \code{post.cutoff}.
#'
#' @author Aaron Taudt
#' @param model A \code{\link{uniHMM}} or \code{\link{multiHMM}} object with posteriors.
#' @param post.cutoff A vector of posterior cutoff values between 0 and 1 the same length as \code{ncol(model$bins$posteriors)}. If only one value is given, it will be reused for all columns. Values close to 1 will yield more stringent peak calls with lower false positive but higher false negative rate.
#' @return The input object is returned with adjusted peak calls.
#' @export
#' @seealso \code{\link{changeMaxPostCutoff}}
#' @examples
#'## Get an example BAM file with ChIP-seq reads
#'file <- system.file("extdata", "euratrans",
#' "lv-H3K27me3-BN-male-bio2-tech1.bam",
#' package="chromstaRData")
#'## Bin the BED file into bin size 1000bp
#'data(rn4_chrominfo)
#'data(experiment_table)
#'binned <- binReads(file, experiment.table=experiment_table,
#' assembly=rn4_chrominfo, binsizes=1000,
#' stepsizes=500, chromosomes='chr12')
#'plotHistogram(binned)
#'## Fit HMM
#'model <- callPeaksUnivariate(binned, keep.posteriors=TRUE, verbosity=0)
#'## Compare fits with different post.cutoffs
#'plotHistogram(changePostCutoff(model, post.cutoff=0.01)) + ylim(0,0.25)
#'plotHistogram(model) + ylim(0,0.25)
#'plotHistogram(changePostCutoff(model, post.cutoff=0.99)) + ylim(0,0.25)
#'
#'## Get an example multiHMM ##
#'file <- system.file("data","multivariate_mode-combinatorial_condition-SHR.RData",
#' package="chromstaR")
#'model <- get(load(file))
#'genomicFrequencies(model)
#'model.new <- changePostCutoff(model, post.cutoff=0.9999)
#'genomicFrequencies(model.new)
#'
#'## Get an example combinedMultiHMM ##
#'file <- system.file("data","combined_mode-differential.RData",
#' package="chromstaR")
#'model <- get(load(file))
#'genomicFrequencies(model)
#'model.new <- changePostCutoff(model, post.cutoff=0.9999)
#'genomicFrequencies(model.new)
#'
changePostCutoff <- function(model, post.cutoff=0.5) {
if (!is.numeric(post.cutoff)) {
warning("'post.cutoff' is not numeric. Nothing done.")
return(model)
}
if (is(model, class.univariate.hmm)) {
model.new <- changePostCutoff.univariate(model=model, post.cutoff=post.cutoff)
} else if (is(model, class.multivariate.hmm) | is(model, class.combined.multivariate.hmm)) {
model.new <- changePostCutoff.multivariate(model=model, post.cutoff=post.cutoff)
}
return(model.new)
}
changePostCutoff.multivariate <- function(model, post.cutoff) {
## Make post.cutoff vector
if (is.null(model$bins$posteriors)) stop("Cannot recalculate states because posteriors are missing.")
numcol <- ncol(model$bins$posteriors)
if (length(post.cutoff) == 1) {
post.cutoff <- rep(post.cutoff, numcol)
}
if (length(post.cutoff) != numcol) {
stop("Need ", numcol, " values in 'post.cutoff' but only ", length(post.cutoff), " are provided.")
}
for (post.cutoff.i in post.cutoff) {
if (post.cutoff.i < 0 | post.cutoff.i > 1) {
stop("Values for 'post.cutoff' need to be inside the interval [0,1].")
}
}
names(post.cutoff) <- colnames(model$bins$posteriors)
# Check if replicates have the same post.cutoff value
reps <- sub('-rep.*', '', model$info$ID)
if (any(sapply(split(post.cutoff, reps), function(x) { Reduce('&', x==x[1]) }) == FALSE)) {
stop("Replicates must have the same post.cutoff value.")
}
## post.cutoff threshold
threshold <- post.cutoff
### Multivariate HMM ###
if (is(model, class.multivariate.hmm)) {
## Calculate states
ptm <- startTimedMessage("Calculating states from posteriors ...")
post <- model$bins$posteriors
post.thresholded <- matrix(FALSE, ncol=ncol(post), nrow=nrow(post))
for (icol in 1:ncol(post)) {
post.thresholded[,icol] <- post[,icol] >= threshold[icol]
}
states <- factor(bin2dec(post.thresholded), levels=levels(model$bins$state))
model$bins$state <- states
## Combinations
if (!is.null(model$bins$combination)) {
mapping <- model$mapping
model$bins$combination <- factor(mapping[as.character(model$bins$state)], levels=mapping[as.character(levels(model$bins$state))])
}
stopTimedMessage(ptm)
## Redo segmentation
model$segments <- multivariateSegmentation(model$bins, column2collapseBy='state')
## Add differential score ##
ptm <- startTimedMessage("Adding differential score ...")
model$segments$differential.score <- differentialScoreSum(model$segments$maxPostInPeak, model$infos)
stopTimedMessage(ptm)
## Maximum posterior in peaks ##
ptm <- startTimedMessage("Getting maximum posterior in peaks ...")
ind <- findOverlaps(model$bins, model$segments)
model$bins$maxPostInPeak <- model$segments$maxPostInPeak[subjectHits(ind), , drop=FALSE]
model$bins$differential.score <- model$segments$differential.score[subjectHits(ind)]
stopTimedMessage(ptm)
## Redo peaks
ptm <- startTimedMessage("Recalculating peaks ...")
model$peaks <- list()
for (i1 in 1:ncol(model$segments$maxPostInPeak)) {
mask <- model$segments$maxPostInPeak[,i1] > 0
peaks <- model$segments[mask]
mcols(peaks) <- NULL
peaks$maxPostInPeak <- model$segments$maxPostInPeak[mask,i1]
model$peaks[[i1]] <- peaks
}
names(model$peaks) <- colnames(model$segments$maxPostInPeak)
stopTimedMessage(ptm)
} else if (is(model, class.combined.multivariate.hmm)) {
ptm <- startTimedMessage("Calculating states from posteriors ...")
post <- model$bins$posteriors
post.thresholded <- matrix(FALSE, ncol=ncol(post), nrow=nrow(post))
for (icol in 1:ncol(post)) {
post.thresholded[,icol] <- post[,icol] >= threshold[icol]
}
decstates <- bin2dec(post.thresholded)
binary.matrix <- post.thresholded[!duplicated(decstates),]
mapping.df <- stateBrewer(model$info[,setdiff(names(model$info), 'ID')], mode='full', binary.matrix = binary.matrix)
mapping <- mapping.df$combination
names(mapping) <- mapping.df$state
states <- factor(decstates, levels=mapping.df$state)
stopTimedMessage(ptm)
## Make fake multiHMM
multiHMM <- list()
class(multiHMM) <- class.multivariate.hmm
multiHMM$info <- model$info
multiHMM$bins <- model$bins
multiHMM$bins$combination <- mapping[as.character(states)]
multiHMM$bins$state <- factor(states)
multiHMM$bins$posteriors <- post
## Redo maxPostInPeak
ptm <- startTimedMessage("Re-estimating maximum posterior in peaks ...")
multiHMM$bins$maxPostInPeak <- getMaxPostInPeaks(multiHMM$bins$state, multiHMM$bins$posteriors)
stopTimedMessage(ptm)
multiHMM$mapping <- mapping
multiHMM$peaks <- model$peaks
model <- combineMultivariates(list(multiHMM), mode='full')
## Redo peaks
ptm <- startTimedMessage("Recalculating peaks ...")
model$peaks <- list()
for (i1 in 1:ncol(model$segments$maxPostInPeak)) {
mask <- model$segments$maxPostInPeak[,i1] > 0
peaks <- model$segments[mask]
mcols(peaks) <- NULL
peaks$maxPostInPeak <- model$segments$maxPostInPeak[mask,i1]
model$peaks[[i1]] <- peaks
}
names(model$peaks) <- colnames(model$segments$maxPostInPeak)
stopTimedMessage(ptm)
} else {
stop("Supply either a uniHMM, multiHMM or combinedMultiHMM object.")
}
## Return model
model$post.cutoff <- threshold
return(model)
}
changePostCutoff.univariate <- function(model, post.cutoff) {
post.cutoff <- suppressWarnings( as.numeric(post.cutoff) )
if (!is.numeric(post.cutoff) | is.na(post.cutoff)) {
warning("Not changing posterior cutoff because given 'post.cutoff' is not numeric.")
return(model)
} else if (post.cutoff < 0 | post.cutoff > 1) {
warning("post.cutoff has to be inside the interval [0,1]. Nothing done.")
return(model)
}
## post.cutoff threshold
threshold <- post.cutoff
model$post.cutoff <- post.cutoff
if (is.null(model$bins$posteriors) & is.null(model$bins$posterior.modified)) stop("Cannot recalculate states because posteriors are missing. Run 'callPeaksUnivariate' again with option 'keep.posteriors' set to TRUE.")
## Calculate states
ptm <- startTimedMessage("Calculating states from posteriors ...")
if (is.null(model$bins$posteriors)) {
warning("Using column 'posterior.modified' to recalculate states, there will be no state 'zero-inflation' in the output. Run 'callPeaksUnivariate' again with option 'keep.posteriors' set to TRUE to also obtain 'zero-inflation' states.")
states <- rep(2,length(model$bins))
states[ model$bins$posterior.modified>=threshold ] <- 3
} else {
states <- rep(NA,length(model$bins))
states[ model$bins$posteriors[,3]<threshold & model$bins$posteriors[,2]<=model$bins$posteriors[,1] ] <- 1
states[ model$bins$posteriors[,3]<threshold & model$bins$posteriors[,2]>model$bins$posteriors[,1] ] <- 2
states[ model$bins$posteriors[,3]>=threshold ] <- 3
}
states <- state.labels[states]
model$bins$state <- states
stopTimedMessage(ptm)
## Redo maxPostInPeak
ptm <- startTimedMessage("Re-estimating maximum posterior in peaks ...")
model$bins$maxPostInPeak <- getMaxPostInPeaks.univariate(model$bins$state, model$bins$posterior.modified)
stopTimedMessage(ptm)
## Redo segmentation
ptm <- startTimedMessage("Making segmentation ...")
gr <- model$bins
df <- as.data.frame(gr)
red.df <- suppressMessages(collapseBins(df, column2collapseBy='state', columns2drop=c('width', 'posterior.modified', grep('posteriors', names(df), value=TRUE), 'counts', 'counts.rpkm', 'posterior.modified')))
segments <- methods::as(red.df, 'GRanges')
model$peaks <- segments[segments$state == 'modified']
model$peaks$state <- NULL
seqlengths(model$peaks) <- seqlengths(model$bins)[seqlevels(model$peaks)]
stopTimedMessage(ptm)
## Return model
return(model)
}
#' @describeIn changeMaxPostCutoff This function was renamed to 'changeMaxPostCutoff' in chromstaR 1.5.1 but it still available for backwards compatibility.
#' @export
#' @param fdr Same as \code{1-maxPost.cutoff}.
changeFDR <- function(model, fdr=0.01, invert=FALSE) {
warning("Usage of 'changeFDR' is discouraged since chromstaR 1.5.1. Please use 'changeMaxPostCutoff' instead.")
return(changeMaxPostCutoff(model=model, maxPost.cutoff=1-fdr, invert=invert))
}
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