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| 1 | +## Function for discovering cell-specific miRNA-miRNA positive correlation |
| 2 | +# miR1 and miR2: Gene expression values of two miRNAs in single cells |
| 3 | +# cell_index: Index of single cells |
| 4 | +# boxsize: Size of neighborhood (0.1 in default) |
| 5 | +# interp_betw_point: The number of interpolation points between each cell (5 in default), interp_betw_point = 0 is used to compute |
| 6 | +# the normalized statistic of edge gx-gy in large number of cells (more than 100) |
| 7 | +# bootstrap_num: The number of bootstrapping for interpolating pseudo-cells |
| 8 | +# Output: res is a list of cell-specific miRNA-miRNA positive correlation |
| 9 | +CSmiRsyn_edge_bootstrap <- function(miR1, miR2, cell_index, boxsize = 0.1, bootstrap_betw_point = 5, bootstrap_num = 100) { |
| 10 | + |
| 11 | + cell_num <- length(miR1) |
| 12 | + set.seed(123) |
| 13 | + bootstrap_sample <- lapply(seq(bootstrap_num), function(i) sample(seq(cell_num), bootstrap_betw_point * (cell_num - 1), replace = TRUE)) |
| 14 | + miR1_bootstrap <- lapply(seq(bootstrap_num), function(i) c(miR1, miR1[bootstrap_sample[[i]]])) |
| 15 | + miR2_bootstrap <- lapply(seq(bootstrap_num), function(i) c(miR2, miR2[bootstrap_sample[[i]]])) |
| 16 | + res <- do.call(pmedian, lapply(seq(bootstrap_num), |
| 17 | + function(k) csn_edge(miR1_bootstrap[[k]], |
| 18 | + miR2_bootstrap[[k]], |
| 19 | + boxsize = boxsize)[seq(cell_num)])) |
| 20 | + |
| 21 | + return(res[cell_index]) |
| 22 | +} |
| 23 | + |
| 24 | +## Identifying cell-specific miRNA synergistic network |
| 25 | +CSmiRsyn_net <- function(miRTarget, cell_index, miRExp, mRExp, minSharedmR = 1, p.value.cutoff = 0.05) { |
| 26 | + |
| 27 | + miRTarget <- as.matrix(miRTarget) |
| 28 | + miRExpNames <- as.matrix(colnames(miRExp)) |
| 29 | + |
| 30 | + miR <- miRTarget[, 1] |
| 31 | + mR <- miRTarget[, 2] |
| 32 | + |
| 33 | + miRSym <- unique(miR) |
| 34 | + mRSym <- unique(mR) |
| 35 | + |
| 36 | + m2 <- length(miRSym) |
| 37 | + |
| 38 | + # Initialize variables |
| 39 | + miRInt <- matrix(NA, m2 * (m2 - 1)/2, 2) |
| 40 | + C <- matrix(NA, m2 * (m2 - 1)/2, 3) |
| 41 | + |
| 42 | + for (i in seq_len(m2 - 1)) { |
| 43 | + for (j in seq(i + 1, m2)) { |
| 44 | + |
| 45 | + Interin1 <- miRTarget[which(miRTarget[, 1] %in% miRSym[i]), 2] |
| 46 | + Interin2 <- miRTarget[which(miRTarget[, 1] %in% miRSym[j]), 2] |
| 47 | + |
| 48 | + M1 <- length(Interin1) |
| 49 | + M2 <- length(Interin2) |
| 50 | + M3 <- length(intersect(Interin1, Interin2)) |
| 51 | + M4 <- length(mRSym) |
| 52 | + M5 <- 1 - phyper(M3 - 1, M2, M4 - M2, M1) |
| 53 | + |
| 54 | + if (M3 >= minSharedmR & M5 < p.value.cutoff) { |
| 55 | + |
| 56 | + miRInt[(i - 1) * m2 + j - sum(seq_len(i)), 1] <- miRSym[i] |
| 57 | + miRInt[(i - 1) * m2 + j - sum(seq_len(i)), 2] <- miRSym[j] |
| 58 | + |
| 59 | + miRExpIdx1 <- which(miRExpNames %in% miRSym[i]) |
| 60 | + miRExpIdx2 <- which(miRExpNames %in% miRSym[j]) |
| 61 | + |
| 62 | + # Calculate cell-specific correlation of each miRNA-miRNA pair |
| 63 | + M6 <- CSmiRsyn_edge_bootstrap(miRExp[, miRExpIdx1], miRExp[, miRExpIdx2], cell_index) |
| 64 | + M7 <- pnorm(-M6) |
| 65 | + |
| 66 | + C[(i - 1) * m2 + j - sum(seq_len(i)), 1] <- M5 |
| 67 | + C[(i - 1) * m2 + j - sum(seq_len(i)), 2] <- M6 |
| 68 | + C[(i - 1) * m2 + j - sum(seq_len(i)), 3] <- M7 |
| 69 | + |
| 70 | + } |
| 71 | + } |
| 72 | + } |
| 73 | + |
| 74 | + # Extract miRNA-miRNA pairs |
| 75 | + miRInt <- miRInt[which((C[, 1] < p.value.cutoff & C[, 3] < p.value.cutoff) == "TRUE"), ] |
| 76 | + |
| 77 | + C <- C[which((C[, 1] < p.value.cutoff & C[, 3] < p.value.cutoff) == "TRUE"), ] |
| 78 | + |
| 79 | + if (is.vector(C)) { |
| 80 | + res_miRInt <- c(miRInt, C) |
| 81 | + names(res_miRInt) <- c("miRNA_1", "miRNA_2", "p_value of shared mRNAs", "correlation", "p_value of correlation") |
| 82 | + |
| 83 | + } else { |
| 84 | + res_miRInt <- cbind(miRInt, C) |
| 85 | + colnames(res_miRInt) <- c("miRNA_1", "miRNA_2", "p_value of shared mRNAs", "correlation", "p_value of correlation") |
| 86 | + } |
| 87 | + |
| 88 | + return(res_miRInt) |
| 89 | +} |
| 90 | + |
| 91 | +## Function for calculating similarity matrix between two list of module groups |
| 92 | +# Module.group1: List object, the first list of module group |
| 93 | +# Module.group2: List object, the second list of module group |
| 94 | +# Output: Sim is a similarity matrix between two list of module groups |
| 95 | +Sim.module.group <- function(Module.group1, Module.group2){ |
| 96 | + |
| 97 | + if(class(Module.group1)!="list" | class(Module.group2)!="list") { |
| 98 | + stop("Please check your input module group! The input module group should be list object! \n") |
| 99 | + } |
| 100 | + |
| 101 | + m <- length(Module.group1) |
| 102 | + n <- length(Module.group2) |
| 103 | + Sim <- matrix(NA, m, n) |
| 104 | + |
| 105 | + for (i in seq(m)){ |
| 106 | + for (j in seq(n)){ |
| 107 | + overlap_interin <- length(intersect(Module.group1[[i]], Module.group2[[j]])) |
| 108 | + Sim[i, j] <- overlap_interin/min(length(Module.group1[[i]]), length(Module.group2[[j]])) |
| 109 | + } |
| 110 | + } |
| 111 | + |
| 112 | + if (m < n) { |
| 113 | + GS <- mean(unlist(lapply(seq(m), function(i) Sim[i, max.col(Sim)[i]])))*m/n |
| 114 | + } else if (m == n) { |
| 115 | + GS <- mean(c(unlist(lapply(seq(m), function(i) Sim[i, max.col(Sim)[i]])), |
| 116 | + unlist(lapply(seq(n), function(i) Sim[max.col(t(Sim))[i], i])))) |
| 117 | + } else if (m > n) { |
| 118 | + GS <- mean(unlist(lapply(seq(n), function(i) Sim[max.col(t(Sim))[i], i])))*n/m |
| 119 | + } |
| 120 | + |
| 121 | + return(GS) |
| 122 | +} |
| 123 | + |
| 124 | +## Function for calculating cluster coefficients in random networks |
| 125 | +# nodes.num: The number of nodes |
| 126 | +# edges.num: The number of edges |
| 127 | +# perm: The number of permutation |
| 128 | +# directed: Logical value, false or true |
| 129 | +# Output: Mean and std of cluster coefficients in random networks |
| 130 | +Random_net_clusterCoeff <- function(nodes.num, edges.num, perm = 10000, directed = FALSE) { |
| 131 | + set.seed(123) |
| 132 | + res <- c() |
| 133 | + for (i in seq(perm)) { |
| 134 | + g <- sample_pa(n = nodes.num, m = edges.num, directed = directed) |
| 135 | + g <- delete_edges(g, sample(1:gsize(g), size = gsize(g) - edges.num)) |
| 136 | + res[i] <- transitivity(g, type="average") |
| 137 | + } |
| 138 | + |
| 139 | + return(list(mean(res), sd(res))) |
| 140 | +} |
| 141 | + |
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