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#' @title Separation
#' @description Calculates the separation of two set of targets on a network.
#' Often used to measure separation of disease modules in a interactome.
#' Separation is calculated as in Menche, J. et al (2015) <doi:10.1126/science.1257601>.
#' @param G The original graph (often an interactome).
#' @param ST Set-Target data. It is a data.frame with two columns. ID and Target.
#'
#' @importFrom magrittr `%>%` `%<>%`
#' @importFrom igraph shortest.paths graph_from_data_frame bipartite_mapping degree V E as_incidence_matrix induced_subgraph
#' @importFrom dplyr filter
#' @return the separation and distance of modules.
#' @export
#' @examples
#' require(magrittr)
#' set.seed(12)
#' x = data.frame(n1 = sample(LETTERS[1:5]),
#' n2 = sample(LETTERS[1:20]))
#'
#' D1 = data.frame(gene = c("H", "I", "S", "N", "A"), disease = "D1")
#' D2 = data.frame(gene = c("E", "C", "R" , "J", "Q", "O"), disease = "D2")
#' D3 = data.frame(gene = c("E", "G", "T", "P"), disease = "D3")
#' D4 = data.frame(gene = c("A", "B", "E"), disease = "D4")
#'
#' Diseases = rbind(D1, D2, D3, D4)
#' Diseases %<>% dplyr::select(disease, gene)
#' g = igraph::graph_from_data_frame(x, directed = FALSE)
#' g = igraph::simplify(g)
#'
#' separation(G = g, ST = Diseases)
separation = function(G, ST){
names(ST)[1:2] = c("ID", "Target")
ST$Target %<>% as.character()
ST %<>% dplyr::filter(Target %in% V(G)$name)
d = ST$ID %>% unique()
asp = igraph::shortest.paths(G, v=unique(ST$Target), to = unique(ST$Target))
# S_aa = list()
S_ab = S_ab.tmp = matrix(NA, ncol = length(d), nrow = length(d))
pb <- txtProgressBar(min = 0, max = (length(d)), style = 3)
for(i in 1:length(d)){
setTxtProgressBar(pb, i)
g_a = ST$Target[ST$ID == d[i]]
# S_aa[[i]] = asp[g_a, g_a][upper.tri(asp[g_a, g_a])] %>% mean()
tmp = asp[g_a, g_a]#[upper.tri(asp[g_a, g_a], diag = F)]
diag(tmp) <- Inf
tmp = apply(tmp,1,min)
tmp = tmp[!is.infinite(tmp)] %>% mean
S_ab.tmp[i,i] = tmp
# S_ab.tmp[i,i] = tmp[!is.infinite(tmp)] %>% mean
j = i + 1
# for(j in (i + 1):length(d)){
# if(j <= length(d)){
while(j <= length(d)){
g_b = ST$Target[ST$ID == d[j]]
tmp = asp[g_a, g_b]#[upper.tri(asp[g_a, g_a], diag = F)]
# tmp = tmp[!is.infinite(tmp)]
# diag(tmp) <- Inf
t1 = apply(tmp,1,min)
t2 = apply(tmp,2,min)
# tmp = sum(t1[!is.infinite(t1)]) + sum(t2[!is.infinite(t2)])
# tmp = tmp/(length(g_a)+length(g_b))
tmp = c(t1, t2)
tmp = mean(tmp[!is.infinite(tmp)])
S_ab.tmp[i,j] = tmp
j = j + 1
}
# S_ab.tmp[i,j] = tmp[!is.infinite(tmp)] %>% mean
# }
# }
}
close(pb)
message("Calculating S_ab..\n")
### calculate the sabs
pb <- txtProgressBar(min = 0, max = (length(d)), style = 3)
for(i in 1:length(d)){
setTxtProgressBar(pb, i)
for(j in 1:length(d)){
S_ab[i,j] = S_ab.tmp[i,j] - mean(c(S_ab.tmp[i,i], S_ab.tmp[j,j]))
}
}
close(pb)
message("Done..\n")
colnames(S_ab)= rownames(S_ab) = d
colnames(S_ab.tmp)= rownames(S_ab.tmp) = d
return(list(Sab = S_ab, Dab = S_ab.tmp))
}
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