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#' main function for Snowball analysis
#'
#' This is the main function to perform snowball analysis. It requires a minimum input with many default operating parameters set.
#'
#' @param y a factor variable for mutation status
#' @param X data.frame containing gene expression data. The columns of \code{X} should be aligned with \code{y} on samples
#' @param ncore number of processors to use for parallel computation. Set \code{ncore = 1} or \code{NULL} for non-parallel computation mode
#' @param d the size of gene subset for gene level resampling. See references on \eqn{d} in \eqn{X_d^x}
#' @param B bootstrap size, which is \eqn{B} in \eqn{J_n(x)}, defining the total number of gene subsets used to estimate \eqn{J_n},
#' \deqn{J_n(x)=\frac{1}{B}\sum_{i=1}^{B}(\frac{1}{K}\sum_{j=1}^{K}\phi_n(g(X_{i,j}),\kappa))}
#' @param B.i bootstrap size deployed on each child job in parallel mode
#' @param sample.n number of samples drawn from the subject level resampling, denoted as \eqn{K} in \eqn{J_n(x)}. It is ignored if \code{resample.method="none"} or \code{"combn"}
#' @param resample.method this defines how the subject level resampling is performed.
#' The possible values are \code{"sample"}, \code{"none"} and \code{"combn"}.
#' Let \code{resample.method = "sample"} for random sampling with replacement,
#' \code{"none"} for no resampling on subject dimension, and \code{"combn"} for
#' all combinations by permuting the subjects in each group. See Note for more information.
#' @param mode.resample this specifies how the subjects are counted for subject
#' level leave-k-out random sampling, and whether the stratification by group is
#' applied. The possible input values are \code{"count.class"}, \code{"percent.class"}
#' or \code{"no"}. \code{"no"} implies that no stratification is applied and the resampling
#' is performed on all subjects pooled together from the both groups. \code{"count.class"}
#' implies the resampling leaves out a subset of subjects based on the number provided,
#' and \code{"percent.class"} implies the number of subjects left out was
#' calculated based on the percentage of the total subjects in each group. See Note for more information.
#' @param k.resample A numerical value specifies the number of subjects left out during the
#' subject level resampling. It is an integer number if \code{mode.resample = "count.class"}
#' and a numerical number between 0 and 1 if \code{mode.resample} = "percent.class". See Note for more information.
#' @note The resampling is applied on two dimensions (see references): gene level resamping and subject level resampling.
#' The gene level resampling is straightforward - each time it takes \code{d} number of genes
#' randomly from all the genes in \code{X}. The subject level resampling is specified by the
#' combination of values given in \code{sample.n}, \code{resample.method}, \code{mode.resample}
#' and \code{k.resample}. The flat resampling on all subjects regardless of grouping, specified by letting
#' \code{resample.method="none"}, is simply a leave-k-out random sampling, where k is given by \code{k.resample}.
#' In more complex cases, the subject level resampling can be stratified based on the groups defined on \code{y},
#' in which case, \code{resample.method} takes the value of either \code{"sample"} or \code{"combn"}.
#' When \code{resample.method = "sample"}, it applies a leave-k-out random sampling within each
#' group and finally only \code{sample.n} samples are generated from the resampling. When \code{resample.method = "combn"},
#' all possible combinations after conditioning on the restrictions given by \code{mode.resample} and
#' \code{k.resample} are included. In this case, the total number of resampled samples varies
#' depending on the sample size of the study. \code{mode.resample="count.class"} or \code{"percent.class"}
#' defines two ways to calculate the number of subjects to be left out in the
#' random sampling. The value of "count.class" indicates the exact number
#' to be left out and "percent.class" indicates the percentage of total subjects to be left out.
#' In all cases, \code{k.resample} specifies the number of subjects left out in the leave-k-out sampling.
#' If \code{k.resample} is only a scalar integer number, the subjects
#' will be sampled with exactly \code{k.resample} subjects left out, either across all the subjects in the case of
#' flat sampling, or within each group in the case of stratified resampling by group. Instead,
#' if \code{k.resample} a vector with two integer numbers, the sampling will leave out the
#' number of subjects from the two groups based on the two numbers provided. The order of which
#' number is taken for which group is based on that the first number is assigned to the first
#' factor level and the second number is assigned to the second factor level of \code{factor(y)}.
#' Check \code{factor(y)} to see how the two numbers in \code{k.resample} would be assigned
#' to the two groups. A vector with two values for \code{k.resample} produces error if \code{mode.resample = "flat"}.
#' This flexible way of defining the sampling scheme allows easy specification for
#' balanced sample size between groups. See references for more details.
#' @return A data.frame containing two variables: \code{weights} and \code{positives}.
#' \code{weights} are the \eqn{J_n(x)} values for all genes and positives are indicators to
#' whether a specific \eqn{J_n(x)} is above or below the median of all \eqn{J_n(x)}'s.
#' @export
#' @examples
#' require(DESnowball)
#' data(snowball.demoData)
#' # check the demo dataset
#' print(sb.mutation)
#' head(sb.expression)
#' ## A test run
#' Bn <- 10000
#' ncore <-4
#' # call Snowball
#'\dontrun{
#' sb <- snowball(y=sb.mutation,X=sb.expression,
#' ncore=ncore,d=100,B=Bn,
#' sample.n=1)
#' # process the gene ranking and selection
#' sb.sel <- select.features(sb)
#' # plot the Jn values
#' plotJn(sb, sb.sel)
#' # get the significant gene list
#' top.genes <- toplist(sb.sel)
#'}
#' @references
#' Xu, Y., Guo, X., Sun, J. and Zhao. Z. Snowball: resampling combined with distance-based regression to discover transcriptional consequences of driver mutation, manuscript.
snowball <- function(y,
X,
ncore=1,
d=300,
B=10000,
B.i=2000,
sample.n=100,
resample.method = c("sample","none","combn"),
mode.resample = c("count.class","flat","percent.class"),
k.resample = 1)
{
## check inputs
if(!is(y,"factor")) y <- as.factor(y)
stopifnot(nlevels(y)==2)
stopifnot(length(y)==ncol(X))
## define operating parameters
dat <- X
d <- d
B <- B
k <- 2
classlabel <- y
method.phi <- "gdbr"
method.dist <- "pearson"
leave.k.out <- resample.method
leave.by <- mode.resample
leave.k <- k.resample
## parallel mode?
if(is.null(ncore)) ncore <- 1
## parallel computation
if(ncore > 1) {
## spawn the children with needed parameters exported
cl <- start.para(ncore,
varlist=c('dat',
'd',
'B',
'k',
'classlabel',
'sample.n',
'method.phi',
'method.dist',
'leave.k.out',
'leave.by',
'leave.k'),
)
## on each node, calculate B.i phi values
if(B.i<=0) B.cl <- unlist(lapply(clusterSplit(cl, seq(B)),length))
else B.cl <- c(rep(B.i, B%/%B.i), if(B%%B.i>0) B%%B.i else NULL)
.arg <- parLapply(cl, B.cl, function(x) weight.aggregate(dat=dat,
d=d,
B=x,
k=k,
classlabel=classlabel,
sample.n=sample.n,
method.phi=method.phi,
method.dist=method.dist,
leave.k.out=leave.k.out,
leave.by=leave.by,
leave.k=leave.k))
stop.para(cl)
## campuate Jn
for(i in seq(along=.arg)) {
if(i==1) {
.sum <- .arg[[1]]$sum
.n <- .arg[[1]]$n
} else {
.sum <- .sum+.arg[[i]]$sum
.n <- .n+.arg[[i]]$n
}}
weights <- .sum/.n
} else {
## non-parallel
## calculate phi
weights.agg <- weight.aggregate(dat=dat,
d=d,
B=B,
k=k,
classlabel=classlabel,
sample.n=sample.n,
method.phi=method.phi,
method.dist=method.dist,
leave.k.out=leave.k.out,
leave.by=leave.by,
leave.k=leave.k)
## calculate Jn
weights <- with(weights.agg, sum/n)
}
## report if there is an infufficient resampling, indicated by NA values in weights
if(sum(is.nan(weights))>0) warning("Insufficient resampling!?")
## assign TRUE or FALSE based on phi values is above or below the median value
positives <- (weights>median(weights,na.rm=T))
## output
ret <- data.frame(weights=weights,
positives=positives)
row.names(ret) <- row.names(dat)
ret
}
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