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# Copyright 2012 Paolo Martini <paolo.martini@unipd.it>
#
#
# This file is part of clipper.
#
# clipper is free software: you can redistribute it and/or modify
# it under the terms of the GNU Affero General Public License
# version 3 as published by the Free Software Foundation.
#
# clipper is distributed in the hope that it will be useful,
# but WITHOUT ANY WARRANTY; without even the implied warranty of
# MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
# GNU Affero General Public License for more details.
#
# You should have received a copy of the GNU Affero General Public
# License along with clipper. If not, see <http://www.gnu.org/licenses/>.
computeTestValue <- function(e1, e2, performPerm=FALSE) {
e.diff <- e1 - e2
e.num <- nrow(e1)
if (performPerm) { # permutations. We sample a sign matrix of -1,1 of length = gene length and nrow = to the number of samples.
signs <- matrix(sample(c(1,-1), e.num * NCOL(e1), replace=TRUE),
nrow=e.num)
e.diff <- e.diff * signs
}
e.bar <- colMeans(e.diff)
e.centr <- e.diff - e.bar
if (e.num <= ncol(e1)) {
e.s <- unclass(cov.shrink(e.centr, verbose=FALSE))
} else {
e.s <- (t(e.centr) %*% e.centr) / e.num
}
t2 <- tryCatch(e.num * (t(e.bar) %*% solve(e.s) %*% e.bar), error=function(e) return(NA))
if (is.matrix(t2))
t2 <- t2[1,1]
return(t2)
}
cliquePairedTest <- function(expr, classes, graph, nperm, alphaV=0.05, b=100, root=NULL, permute=TRUE, alwaysShrink=FALSE) {
expr <- getExpression(expr, classes)
if (sum(classes==1) != sum(classes==2)) {
stop("Your are working woth paired mode. The number of samples per class must be equal (and paired).")
}
genes <- nodes(graph)
genes <- intersect(genes, colnames(expr))
if (length(genes)== 0)
stop("There is no intersection between expression feature names and the node names on the graph.")
graph <- subGraph(genes, graph)
expr <- expr[, genes, drop=FALSE]
cvt <- runVarianceTest(expr, classes, graph, nperm, root, permute, alwaysShrink)
if (is.null(cvt)){
return(NULL)
}
check <- cvt$alpha <= alphaV
cliques <- cvt$cliques
maxcliques <- max(sapply(cliques, length))
ncl1 <- sum(classes==2)
ncl2 <- sum(classes==1)
alpha <- sapply(seq_along(cliques), function(i) {
genes <- unlist(cliques[i])
e <- expr[, genes, drop=FALSE]
e1 <- e[classes==2,, drop=FALSE]
e2 <- e[classes==1,, drop=FALSE]
if (length(genes) == 1)
t.test(e1, e2, paired=TRUE)$p.value
else {
e.num <- nrow(e1)
p <- ncol(e1)
np <- e.num - p # This is the transposed matrix; e.num is the number of samples; p the number of genes
t2obs <- computeTestValue(e1, e2)
if (np > 0) { # see if this option should be true when permute=TRUE
t.value <- t2obs * np / (p * (e.num-1))
1-pf(t.value, p, np)
} else {
t2perm <- vector("numeric", nperm)
for (i in seq_len(nperm)) {
t2perm[i] <- computeTestValue(e1, e2, performPerm=TRUE)
}
sum(t2perm >= t2obs) / nperm
}
}
})
list(alpha=alpha, cliques=cliques)
}
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