tests/testthat/test_graphSpatialFDR.R
In MikeDMorgan/miloR: Differential neighbourhood abundance testing on a graph
context("Test spatialFDR function")
library(miloR)
### Set up a mock data set using simulated data
library(SingleCellExperiment)
library(scran)
library(scater)
library(irlba)
library(MASS)
library(mvtnorm)
set.seed(42)
r.n <- 1000
n.dim <- 50
block1.cells <- 500
# select a set of eigen values for the covariance matrix of each block, say 50 eigenvalues?
block1.eigens <- sapply(1:n.dim, FUN=function(X) rexp(n=1, rate=abs(runif(n=1, min=0, max=50))))
block1.eigens <- block1.eigens[order(block1.eigens)]
block1.p <- qr.Q(qr(matrix(rnorm(block1.cells^2, mean=4, sd=0.01), block1.cells)))
block1.sigma <- crossprod(block1.p, block1.p*block1.eigens)
block1.gex <- abs(rmvnorm(n=r.n, mean=rnorm(n=block1.cells, mean=2, sd=0.01), sigma=block1.sigma))
block2.cells <- 500
# select a set of eigen values for the covariance matrix of each block, say 50 eigenvalues?
block2.eigens <- sapply(1:n.dim, FUN=function(X) rexp(n=1, rate=abs(runif(n=1, min=0, max=50))))
block2.eigens <- block2.eigens[order(block2.eigens)]
block2.p <- qr.Q(qr(matrix(rnorm(block2.cells^2, mean=4, sd=0.01), block2.cells)))
block2.sigma <- crossprod(block2.p, block2.p*block2.eigens)
block2.gex <- abs(rmvnorm(n=r.n, mean=rnorm(n=block2.cells, mean=4, sd=0.01), sigma=block2.sigma))
block3.cells <- 650
# select a set of eigen values for the covariance matrix of each block, say 50 eigenvalues?
block3.eigens <- sapply(1:n.dim, FUN=function(X) rexp(n=1, rate=abs(runif(n=1, min=0, max=50))))
block3.eigens <- block3.eigens[order(block3.eigens)]
block3.p <- qr.Q(qr(matrix(rnorm(block3.cells^2, mean=4, sd=0.01), block3.cells)))
block3.sigma <- crossprod(block3.p, block3.p*block3.eigens)
block3.gex <- abs(rmvnorm(n=r.n, mean=rnorm(n=block3.cells, mean=5, sd=0.01), sigma=block3.sigma))
sim1.gex <- do.call(cbind, list("b1"=block1.gex, "b2"=block2.gex, "b3"=block3.gex))
colnames(sim1.gex) <- paste0("Cell", 1:ncol(sim1.gex))
rownames(sim1.gex) <- paste0("Gene", 1:nrow(sim1.gex))
sim1.pca <- prcomp_irlba(t(sim1.gex), n=50, scale.=TRUE, center=TRUE)
set.seed(42)
block1.cond <- rep("A", block1.cells)
block1.a <- sample(1:block1.cells, size=floor(block1.cells*0.9))
block1.b <- setdiff(1:block1.cells, block1.a)
block1.cond[block1.b] <- "B"
block2.cond <- rep("A", block2.cells)
block2.a <- sample(1:block2.cells, size=floor(block2.cells*0.05))
block2.b <- setdiff(1:block2.cells, block2.a)
block2.cond[block2.b] <- "B"
block3.cond <- rep("A", block3.cells)
block3.a <- sample(1:block3.cells, size=floor(block3.cells*0.5))
block3.b <- setdiff(1:block3.cells, block3.a)
block3.cond[block3.b] <- "B"
meta.df <- data.frame("Block"=c(rep("B1", block1.cells), rep("B2", block2.cells), rep("B3", block3.cells)),
"Condition"=c(block1.cond, block2.cond, block3.cond),
"Replicate"=c(rep("R1", floor(block1.cells*0.33)), rep("R2", floor(block1.cells*0.33)),
rep("R3", block1.cells-(2*floor(block1.cells*0.33))),
rep("R1", floor(block2.cells*0.33)), rep("R2", floor(block2.cells*0.33)),
rep("R3", block2.cells-(2*floor(block2.cells*0.33))),
rep("R1", floor(block3.cells*0.33)), rep("R2", floor(block3.cells*0.33)),
rep("R3", block3.cells-(2*floor(block3.cells*0.33)))))
colnames(meta.df) <- c("Block", "Condition", "Replicate")
# define a "sample" as teh combination of condition and replicate
meta.df$Sample <- paste(meta.df$Condition, meta.df$Replicate, sep="_")
meta.df$Vertex <- c(1:nrow(meta.df))
sim1.sce <- SingleCellExperiment(assays=list(logcounts=sim1.gex),
reducedDims=list("PCA"=sim1.pca$x))
sim1.mylo <- Milo(sim1.sce)
# build a graph - this can take a while for large graphs - will need to play
# around with the parallelisation options
sim1.mylo <- buildGraph(sim1.mylo, k=21, d=30)
# define neighbourhoods - this is slow for large data sets
# how can this be sped up? There are probably some parallelisable steps
sim1.mylo <- makeNhoods(sim1.mylo, k=21, prop=0.1, refined=TRUE,
d=30,
reduced_dims="PCA")
sim1.mylo <- calcNhoodDistance(sim1.mylo, d=30)
sim1.meta <- data.frame("Condition"=c(rep("A", 3), rep("B", 3)),
"Replicate"=rep(c("R1", "R2", "R3"), 2))
sim1.meta$Sample <- paste(sim1.meta$Condition, sim1.meta$Replicate, sep="_")
rownames(sim1.meta) <- sim1.meta$Sample
sim1.mylo <- countCells(sim1.mylo, samples="Sample", meta.data=meta.df)
test_that("Incorrect parameter values produce errors", {
# call outside of testNhoods function
da.ref <- testNhoods(sim1.mylo, design=~Condition,
fdr.weighting="none",
design.df=sim1.meta[colnames(nhoodCounts(sim1.mylo)), ])
expect_error(graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=miloR::graph(sim1.mylo),
weighting="neighbour-distance",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=NULL),
"A matrix of reduced dimensions")
expect_error(graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="k-distance",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=NULL,
k=sim1.mylo@.k,
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=NULL),
"No neighbourhood indices found")
expect_error(graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="k-distance",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
k=sim1.mylo@.k,
distances=NULL,
reduced.dimensions=NULL),
"k-distance weighting requires")
expect_error(graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="blah",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=reducedDim(sim1.mylo, "PCA")),
"Weighting option not recognised")
})
test_that("Input 'none' produces NAs", {
da.ref <- testNhoods(sim1.mylo, design=~Condition,
fdr.weighting="none",
design.df=sim1.meta[colnames(nhoodCounts(sim1.mylo)), ])
out.p <- graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="none",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=reducedDim(sim1.mylo, "PCA"))
expect_true(sum(is.na(out.p)) == length(out.p))
})
test_that("graphSpatialFDR produces reproducible results for neighbour-distance weighting", {
# calculate spatial FDR here using the actual code
da.ref <- testNhoods(sim1.mylo, design=~Condition,
fdr.weighting="none",
design.df=sim1.meta[colnames(nhoodCounts(sim1.mylo)), ])
nhoods <- nhoods(sim1.mylo)
graph <- graph(sim1.mylo)
reduced.dimensions <- reducedDim(sim1.mylo, "PCA")
pvalues <- da.ref[order(da.ref$Nhood), ]$PValue
haspval <- !is.na(pvalues)
if (!all(haspval)) {
coords <- coords[haspval, , drop=FALSE]
pvalues <- pvalues[haspval]
}
t.connect <- sapply(colnames(nhoods)[haspval],
FUN=function(PG) {
x.pcs <- reduced.dimensions[nhoods[, PG] > 0, ]
x.euclid <- as.matrix(dist(x.pcs))
x.distdens <- mean(x.euclid[lower.tri(x.euclid, diag=FALSE)])
return(x.distdens)})
w <- 1/unlist(t.connect)
w[is.infinite(w)] <- 0
# Computing a density-weighted q-value.
o <- order(pvalues)
pvalues <- pvalues[o]
w <- w[o]
adjp <- numeric(length(o))
adjp[o] <- rev(cummin(rev(sum(w)*pvalues/cumsum(w))))
adjp <- pmin(adjp, 1)
if (!all(haspval)) {
refp <- rep(NA_real_, length(haspval))
refp[haspval] <- adjp
adjp <- refp
}
func.fdr <- graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="neighbour-distance",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=reducedDim(sim1.mylo, "PCA"))
expect_equal(func.fdr, adjp)
})
test_that("graphSpatialFDR produces reproducible results for k-distance weighting", {
# calculate spatial FDR here using the actual code - first with PCA, then distances
da.ref <- testNhoods(sim1.mylo, design=~Condition,
fdr.weighting="none",
design.df=sim1.meta[colnames(nhoodCounts(sim1.mylo)), ])
nhoods <- nhoods(sim1.mylo)
graph <- graph(sim1.mylo)
indices <- nhoodIndex(sim1.mylo)
distances <- nhoodDistances(sim1.mylo)
reduced.dimensions <- reducedDim(sim1.mylo, "PCA")
pvalues <- da.ref[order(da.ref$Nhood), ]$PValue
haspval <- !is.na(pvalues)
if (!all(haspval)) {
coords <- coords[haspval, , drop=FALSE]
pvalues <- pvalues[haspval]
}
k <- sim1.mylo@.k
non.zero.nhoods <- which(nhoods!=0, arr.ind = TRUE)
t.dists <- lapply(indices, FUN=function(X) distances[[as.character(X)]][which(non.zero.nhoods[non.zero.nhoods[,2] == which(indices == X),][,1] == X),])
t.connect <- unlist(lapply(t.dists, FUN=function(Q) (Q[Q>0])[order(Q[Q>0], decreasing=FALSE)[k]]))
#t.connect <- unlist(lapply(indices, FUN=function(X) max(distances[[as.character(X)]])))
w <- 1/unlist(t.connect)
w[is.infinite(w)] <- 0
# Computing a density-weighted q-value.
o <- order(pvalues)
pvalues <- pvalues[o]
w <- w[o]
adjp <- numeric(length(o))
adjp[o] <- rev(cummin(rev(sum(w)*pvalues/cumsum(w))))
adjp <- pmin(adjp, 1)
if (!all(haspval)) {
refp <- rep(NA_real_, length(haspval))
refp[haspval] <- adjp
adjp <- refp
}
func.fdr <- graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="k-distance",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
k=sim1.mylo@.k,
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=reducedDim(sim1.mylo, "PCA"))
expect_equal(func.fdr, adjp)
# with reduced dims
suppressWarnings(require(BiocNeighbors))
pvalues <- da.ref[order(da.ref$Nhood), ]$PValue
haspval <- !is.na(pvalues)
if (!all(haspval)) {
coords <- coords[haspval, , drop=FALSE]
pvalues <- pvalues[haspval]
}
t.connect <- unlist(lapply(indices,
FUN=function(X) max(findKNN(reduced.dimensions,
get.distance=TRUE,
subset=X, k=sim1.mylo@.k)[["distance"]])))
w <- 1/unlist(t.connect)
w[is.infinite(w)] <- 0
# Computing a density-weighted q-value.
o <- order(pvalues)
pvalues <- pvalues[o]
w <- w[o]
adjp <- numeric(length(o))
adjp[o] <- rev(cummin(rev(sum(w)*pvalues/cumsum(w))))
adjp <- pmin(adjp, 1)
if (!all(haspval)) {
refp <- rep(NA_real_, length(haspval))
refp[haspval] <- adjp
adjp <- refp
}
func.fdr <- graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="k-distance",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
k=sim1.mylo@.k,
distances=NULL,
reduced.dimensions=reducedDim(sim1.mylo, "PCA"))
expect_equal(func.fdr, adjp)
})
test_that("graphSpatialFDR produces reproducible results for graph-overlap weighting", {
# calculate spatial FDR here using the actual code
da.ref <- testNhoods(sim1.mylo, design=~Condition,
fdr.weighting="none",
design.df=sim1.meta[colnames(nhoodCounts(sim1.mylo)), ])
nhoods <- nhoods(sim1.mylo)
graph <- graph(sim1.mylo)
reduced.dimensions <- reducedDim(sim1.mylo, "PCA")
pvalues <- da.ref[order(da.ref$Nhood), ]$PValue
haspval <- !is.na(pvalues)
if (!all(haspval)) {
coords <- coords[haspval, , drop=FALSE]
pvalues <- pvalues[haspval]
}
intersect_mat <- crossprod(nhoods)
diag(intersect_mat) <- 0
t.connect <- unname(rowSums(intersect_mat))
w <- 1/unlist(t.connect)
w[is.infinite(w)] <- 0
# Computing a density-weighted q-value.
o <- order(pvalues)
pvalues <- pvalues[o]
w <- w[o]
adjp <- numeric(length(o))
adjp[o] <- rev(cummin(rev(sum(w)*pvalues/cumsum(w))))
adjp <- pmin(adjp, 1)
if (!all(haspval)) {
refp <- rep(NA_real_, length(haspval))
refp[haspval] <- adjp
adjp <- refp
}
func.fdr <- graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="graph-overlap",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=reducedDim(sim1.mylo, "PCA"))
expect_equal(func.fdr, adjp)
})
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context("Test spatialFDR function")
library(miloR)
### Set up a mock data set using simulated data
library(SingleCellExperiment)
library(scran)
library(scater)
library(irlba)
library(MASS)
library(mvtnorm)
set.seed(42)
r.n <- 1000
n.dim <- 50
block1.cells <- 500
# select a set of eigen values for the covariance matrix of each block, say 50 eigenvalues?
block1.eigens <- sapply(1:n.dim, FUN=function(X) rexp(n=1, rate=abs(runif(n=1, min=0, max=50))))
block1.eigens <- block1.eigens[order(block1.eigens)]
block1.p <- qr.Q(qr(matrix(rnorm(block1.cells^2, mean=4, sd=0.01), block1.cells)))
block1.sigma <- crossprod(block1.p, block1.p*block1.eigens)
block1.gex <- abs(rmvnorm(n=r.n, mean=rnorm(n=block1.cells, mean=2, sd=0.01), sigma=block1.sigma))
block2.cells <- 500
# select a set of eigen values for the covariance matrix of each block, say 50 eigenvalues?
block2.eigens <- sapply(1:n.dim, FUN=function(X) rexp(n=1, rate=abs(runif(n=1, min=0, max=50))))
block2.eigens <- block2.eigens[order(block2.eigens)]
block2.p <- qr.Q(qr(matrix(rnorm(block2.cells^2, mean=4, sd=0.01), block2.cells)))
block2.sigma <- crossprod(block2.p, block2.p*block2.eigens)
block2.gex <- abs(rmvnorm(n=r.n, mean=rnorm(n=block2.cells, mean=4, sd=0.01), sigma=block2.sigma))
block3.cells <- 650
# select a set of eigen values for the covariance matrix of each block, say 50 eigenvalues?
block3.eigens <- sapply(1:n.dim, FUN=function(X) rexp(n=1, rate=abs(runif(n=1, min=0, max=50))))
block3.eigens <- block3.eigens[order(block3.eigens)]
block3.p <- qr.Q(qr(matrix(rnorm(block3.cells^2, mean=4, sd=0.01), block3.cells)))
block3.sigma <- crossprod(block3.p, block3.p*block3.eigens)
block3.gex <- abs(rmvnorm(n=r.n, mean=rnorm(n=block3.cells, mean=5, sd=0.01), sigma=block3.sigma))
sim1.gex <- do.call(cbind, list("b1"=block1.gex, "b2"=block2.gex, "b3"=block3.gex))
colnames(sim1.gex) <- paste0("Cell", 1:ncol(sim1.gex))
rownames(sim1.gex) <- paste0("Gene", 1:nrow(sim1.gex))
sim1.pca <- prcomp_irlba(t(sim1.gex), n=50, scale.=TRUE, center=TRUE)
set.seed(42)
block1.cond <- rep("A", block1.cells)
block1.a <- sample(1:block1.cells, size=floor(block1.cells*0.9))
block1.b <- setdiff(1:block1.cells, block1.a)
block1.cond[block1.b] <- "B"
block2.cond <- rep("A", block2.cells)
block2.a <- sample(1:block2.cells, size=floor(block2.cells*0.05))
block2.b <- setdiff(1:block2.cells, block2.a)
block2.cond[block2.b] <- "B"
block3.cond <- rep("A", block3.cells)
block3.a <- sample(1:block3.cells, size=floor(block3.cells*0.5))
block3.b <- setdiff(1:block3.cells, block3.a)
block3.cond[block3.b] <- "B"
meta.df <- data.frame("Block"=c(rep("B1", block1.cells), rep("B2", block2.cells), rep("B3", block3.cells)),
"Condition"=c(block1.cond, block2.cond, block3.cond),
"Replicate"=c(rep("R1", floor(block1.cells*0.33)), rep("R2", floor(block1.cells*0.33)),
rep("R3", block1.cells-(2*floor(block1.cells*0.33))),
rep("R1", floor(block2.cells*0.33)), rep("R2", floor(block2.cells*0.33)),
rep("R3", block2.cells-(2*floor(block2.cells*0.33))),
rep("R1", floor(block3.cells*0.33)), rep("R2", floor(block3.cells*0.33)),
rep("R3", block3.cells-(2*floor(block3.cells*0.33)))))
colnames(meta.df) <- c("Block", "Condition", "Replicate")
# define a "sample" as teh combination of condition and replicate
meta.df$Sample <- paste(meta.df$Condition, meta.df$Replicate, sep="_")
meta.df$Vertex <- c(1:nrow(meta.df))
sim1.sce <- SingleCellExperiment(assays=list(logcounts=sim1.gex),
reducedDims=list("PCA"=sim1.pca$x))
sim1.mylo <- Milo(sim1.sce)
# build a graph - this can take a while for large graphs - will need to play
# around with the parallelisation options
sim1.mylo <- buildGraph(sim1.mylo, k=21, d=30)
# define neighbourhoods - this is slow for large data sets
# how can this be sped up? There are probably some parallelisable steps
sim1.mylo <- makeNhoods(sim1.mylo, k=21, prop=0.1, refined=TRUE,
d=30,
reduced_dims="PCA")
sim1.mylo <- calcNhoodDistance(sim1.mylo, d=30)
sim1.meta <- data.frame("Condition"=c(rep("A", 3), rep("B", 3)),
"Replicate"=rep(c("R1", "R2", "R3"), 2))
sim1.meta$Sample <- paste(sim1.meta$Condition, sim1.meta$Replicate, sep="_")
rownames(sim1.meta) <- sim1.meta$Sample
sim1.mylo <- countCells(sim1.mylo, samples="Sample", meta.data=meta.df)
test_that("Incorrect parameter values produce errors", {
# call outside of testNhoods function
da.ref <- testNhoods(sim1.mylo, design=~Condition,
fdr.weighting="none",
design.df=sim1.meta[colnames(nhoodCounts(sim1.mylo)), ])
expect_error(graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=miloR::graph(sim1.mylo),
weighting="neighbour-distance",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=NULL),
"A matrix of reduced dimensions")
expect_error(graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="k-distance",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=NULL,
k=sim1.mylo@.k,
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=NULL),
"No neighbourhood indices found")
expect_error(graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="k-distance",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
k=sim1.mylo@.k,
distances=NULL,
reduced.dimensions=NULL),
"k-distance weighting requires")
expect_error(graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="blah",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=reducedDim(sim1.mylo, "PCA")),
"Weighting option not recognised")
})
test_that("Input 'none' produces NAs", {
da.ref <- testNhoods(sim1.mylo, design=~Condition,
fdr.weighting="none",
design.df=sim1.meta[colnames(nhoodCounts(sim1.mylo)), ])
out.p <- graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="none",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=reducedDim(sim1.mylo, "PCA"))
expect_true(sum(is.na(out.p)) == length(out.p))
})
test_that("graphSpatialFDR produces reproducible results for neighbour-distance weighting", {
# calculate spatial FDR here using the actual code
da.ref <- testNhoods(sim1.mylo, design=~Condition,
fdr.weighting="none",
design.df=sim1.meta[colnames(nhoodCounts(sim1.mylo)), ])
nhoods <- nhoods(sim1.mylo)
graph <- graph(sim1.mylo)
reduced.dimensions <- reducedDim(sim1.mylo, "PCA")
pvalues <- da.ref[order(da.ref$Nhood), ]$PValue
haspval <- !is.na(pvalues)
if (!all(haspval)) {
coords <- coords[haspval, , drop=FALSE]
pvalues <- pvalues[haspval]
}
t.connect <- sapply(colnames(nhoods)[haspval],
FUN=function(PG) {
x.pcs <- reduced.dimensions[nhoods[, PG] > 0, ]
x.euclid <- as.matrix(dist(x.pcs))
x.distdens <- mean(x.euclid[lower.tri(x.euclid, diag=FALSE)])
return(x.distdens)})
w <- 1/unlist(t.connect)
w[is.infinite(w)] <- 0
# Computing a density-weighted q-value.
o <- order(pvalues)
pvalues <- pvalues[o]
w <- w[o]
adjp <- numeric(length(o))
adjp[o] <- rev(cummin(rev(sum(w)*pvalues/cumsum(w))))
adjp <- pmin(adjp, 1)
if (!all(haspval)) {
refp <- rep(NA_real_, length(haspval))
refp[haspval] <- adjp
adjp <- refp
}
func.fdr <- graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="neighbour-distance",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=reducedDim(sim1.mylo, "PCA"))
expect_equal(func.fdr, adjp)
})
test_that("graphSpatialFDR produces reproducible results for k-distance weighting", {
# calculate spatial FDR here using the actual code - first with PCA, then distances
da.ref <- testNhoods(sim1.mylo, design=~Condition,
fdr.weighting="none",
design.df=sim1.meta[colnames(nhoodCounts(sim1.mylo)), ])
nhoods <- nhoods(sim1.mylo)
graph <- graph(sim1.mylo)
indices <- nhoodIndex(sim1.mylo)
distances <- nhoodDistances(sim1.mylo)
reduced.dimensions <- reducedDim(sim1.mylo, "PCA")
pvalues <- da.ref[order(da.ref$Nhood), ]$PValue
haspval <- !is.na(pvalues)
if (!all(haspval)) {
coords <- coords[haspval, , drop=FALSE]
pvalues <- pvalues[haspval]
}
k <- sim1.mylo@.k
non.zero.nhoods <- which(nhoods!=0, arr.ind = TRUE)
t.dists <- lapply(indices, FUN=function(X) distances[[as.character(X)]][which(non.zero.nhoods[non.zero.nhoods[,2] == which(indices == X),][,1] == X),])
t.connect <- unlist(lapply(t.dists, FUN=function(Q) (Q[Q>0])[order(Q[Q>0], decreasing=FALSE)[k]]))
#t.connect <- unlist(lapply(indices, FUN=function(X) max(distances[[as.character(X)]])))
w <- 1/unlist(t.connect)
w[is.infinite(w)] <- 0
# Computing a density-weighted q-value.
o <- order(pvalues)
pvalues <- pvalues[o]
w <- w[o]
adjp <- numeric(length(o))
adjp[o] <- rev(cummin(rev(sum(w)*pvalues/cumsum(w))))
adjp <- pmin(adjp, 1)
if (!all(haspval)) {
refp <- rep(NA_real_, length(haspval))
refp[haspval] <- adjp
adjp <- refp
}
func.fdr <- graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="k-distance",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
k=sim1.mylo@.k,
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=reducedDim(sim1.mylo, "PCA"))
expect_equal(func.fdr, adjp)
# with reduced dims
suppressWarnings(require(BiocNeighbors))
pvalues <- da.ref[order(da.ref$Nhood), ]$PValue
haspval <- !is.na(pvalues)
if (!all(haspval)) {
coords <- coords[haspval, , drop=FALSE]
pvalues <- pvalues[haspval]
}
t.connect <- unlist(lapply(indices,
FUN=function(X) max(findKNN(reduced.dimensions,
get.distance=TRUE,
subset=X, k=sim1.mylo@.k)[["distance"]])))
w <- 1/unlist(t.connect)
w[is.infinite(w)] <- 0
# Computing a density-weighted q-value.
o <- order(pvalues)
pvalues <- pvalues[o]
w <- w[o]
adjp <- numeric(length(o))
adjp[o] <- rev(cummin(rev(sum(w)*pvalues/cumsum(w))))
adjp <- pmin(adjp, 1)
if (!all(haspval)) {
refp <- rep(NA_real_, length(haspval))
refp[haspval] <- adjp
adjp <- refp
}
func.fdr <- graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="k-distance",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
k=sim1.mylo@.k,
distances=NULL,
reduced.dimensions=reducedDim(sim1.mylo, "PCA"))
expect_equal(func.fdr, adjp)
})
test_that("graphSpatialFDR produces reproducible results for graph-overlap weighting", {
# calculate spatial FDR here using the actual code
da.ref <- testNhoods(sim1.mylo, design=~Condition,
fdr.weighting="none",
design.df=sim1.meta[colnames(nhoodCounts(sim1.mylo)), ])
nhoods <- nhoods(sim1.mylo)
graph <- graph(sim1.mylo)
reduced.dimensions <- reducedDim(sim1.mylo, "PCA")
pvalues <- da.ref[order(da.ref$Nhood), ]$PValue
haspval <- !is.na(pvalues)
if (!all(haspval)) {
coords <- coords[haspval, , drop=FALSE]
pvalues <- pvalues[haspval]
}
intersect_mat <- crossprod(nhoods)
diag(intersect_mat) <- 0
t.connect <- unname(rowSums(intersect_mat))
w <- 1/unlist(t.connect)
w[is.infinite(w)] <- 0
# Computing a density-weighted q-value.
o <- order(pvalues)
pvalues <- pvalues[o]
w <- w[o]
adjp <- numeric(length(o))
adjp[o] <- rev(cummin(rev(sum(w)*pvalues/cumsum(w))))
adjp <- pmin(adjp, 1)
if (!all(haspval)) {
refp <- rep(NA_real_, length(haspval))
refp[haspval] <- adjp
adjp <- refp
}
func.fdr <- graphSpatialFDR(x.nhoods=nhoods(sim1.mylo),
graph=graph(sim1.mylo),
weighting="graph-overlap",
pvalues=da.ref[order(da.ref$Nhood), ]$PValue,
indices=nhoodIndex(sim1.mylo),
distances=nhoodDistances(sim1.mylo),
reduced.dimensions=reducedDim(sim1.mylo, "PCA"))
expect_equal(func.fdr, adjp)
})
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