#' @title Non-partial correlaton analysis
#' @description A method that integrates differential expression (DE) analysis
#' and differential network (DN) analysis to select biomarker candidates for
#' cancer studies. non_partial_cor is a one step function for user
#' to perform the analysis, no pre-processing step required.
#' @param data This is a matrix of expression from all metabolites from all samples.
#' @param class_label this is a binary array with 0 for group 1 and 1 for group 2.
#' @param id This is an array of biomolecule ID to label.
#' @param method This is a character string indicating which correlation coefficient is
#' to be computed. The options are either "pearson" (the default) or "spearman".
#' @param p_val This is optional, it is a data frame containing p-values for each metabolite/molecule.
#' @param permutation This is a positive integer representing the desired number of permutations, default is 1000.
#' @param permutation_thres This is a threshold for permutation. The defalut is 0.025 for each side to result in 95 percent confidience.
#' @examples non_partial_cor(data = Met_GU, class_label = Met_Group_GU, id = Met_name_GU,
#' method = "spearman", permutation_thres = 0.05, permutation = 1000)
#' @return A list containing a score data frame with "MetID", "P_value", "Node_Degree", "Activity_Score"
#' and a differential network data frame with "Node1", "Node2", the binary link value and the weight link value.
#' @import devtools
#' @importFrom glasso glasso
#' @importFrom stats qnorm cor quantile var sd glm
#' @importFrom graphics abline title plot lines
#' @export
non_partial_cor <- function(data = NULL, class_label = NULL, id = NULL, method = "pearson",
p_val = NULL, permutation = 1000, permutation_thres = 0.025){
data_bind <- rbind(data , class_label)
raw_group_1 <- data_bind[,data_bind[nrow(data_bind),] == 0][1:(nrow(data_bind) - 1),] # Group 1: p*n1
raw_group_2 <- data_bind[,data_bind[nrow(data_bind),] == 1][1:(nrow(data_bind) - 1),] # Group 2: p*n2
p <- nrow(raw_group_2)
n_group_2 <- ncol(raw_group_2)
n_group_1 <- ncol(raw_group_1)
# Z-transform the data for group-specific normalization
data_group_1 <- scale(t(raw_group_1)) # Group 1: n1*p
data_group_2 <- scale(t(raw_group_2)) # Group 2: n2*p
cov_group_1 <- var(data_group_1)
cov_group_2 <- var(data_group_2)
if(missing(method)){method="pearson"}
else if(method != "spearman"){method ="pearson"}
cor <- compute_cor(data_group_2, data_group_1, type_of_cor = method) # default is pearson correlation
# Get the correlation matrix
cor_group_2 <- cor$Group2
cor_group_1 <- cor$Group1
# examine the correlation matrix
thres <- 1e-3
sum(abs(cor_group_2) > thres)
cor_group_2[1:10, 1:10]
sum(abs(cor_group_1) > thres)
cor_group_1[1:10, 1:10]
rm(thres)
# Build differential correlation networks
diff <- cor_group_2 - cor_group_1 # from group 1 to group 2
thres = 1e-3
sum(abs(diff) > thres)
diff[1:10, 1:10]
# Permutation test
if(permutation<=0) {stop("please provide a valid number of permutation (positive integer)")}
else{
m <- as.numeric(permutation)
diff_p <- permutation_cor(m, p, n_group_1, n_group_2, data_group_1, data_group_2, type_of_cor = method)
}
# Calculating the positive and negative threshold based on the permutation result
thres_left <- permutation_thres
thres_right <- 1-permutation_thres
significant_thres <- permutation_thres(thres_left, thres_right, p, diff_p)
rm(thres_left, thres_right)
# get binary matrix
significant_thres_p <- significant_thres$positive
significant_thres_n <- significant_thres$negative
binary_link <- matrix(0, p, p) # binary connection
binary_link[diff < significant_thres_n] <- -1
binary_link[diff > significant_thres_p] <- 1
weight_link <- matrix(0, p, p) # weight connection
weight_link[diff < significant_thres_n] <- diff[diff < significant_thres_n]
weight_link[diff > significant_thres_p] <- diff[diff > significant_thres_p]
sum(diff < significant_thres_n)
sum(diff > significant_thres_p)
binary_link[1:10, 1:10]
weight_link[1:10, 1:10]
rowSums(abs(binary_link)) # node degree for differential networks
rm(diff_p)
# Convert adjacent matrix into edge list
i <- rep(seq_len(nrow(binary_link) - 1), times = (nrow(binary_link)-1):1)
k <- unlist(lapply(2:nrow(binary_link), seq, nrow(binary_link)))
binary_link_value <- binary_link[lower.tri(binary_link)]
weight_link_value <- weight_link[lower.tri(weight_link)]
edge <- cbind("Node1" = i, "Node2" = k, "Binary" = binary_link_value, "Weight" = weight_link_value)
edge_dn <- edge[which(edge[,3] != 0),]
edge_dn <- as.data.frame(edge_dn)
if (is.null(p_val) == TRUE) {
# Calculate p-values using logistic regression if p-values are not provided by users
pvalue <- pvalue_logit(data, class_label, id)
p.value <- pvalue$p.value
row.names(pvalue)<-NULL
} else { # If the p-value matrix is provided
pvalue <- p_val
p.value <- pvalue$p.value # Extract p-values from the table provided
row.names(pvalue)<-NULL
}
# trasfer p-value to z-score
z_score <- abs(qnorm(1 - p.value/2))
# calculate differntial network score
dn_score <- compute_dns(binary_link, z_score)
indeed_df <- cbind(pvalue, rowSums(abs(binary_link)), dn_score )
colnames(indeed_df) <- c("MetID", "P_value", "Node_Degree", "Activity_Score")
indeed_df$P_value <- lapply(indeed_df$P_value, round, 3)
indeed_df$Activity_Score <- lapply(indeed_df$Activity_Score, round, 1)
indeed_df <- as.data.frame(lapply(indeed_df, unlist))
indeed_df <- cbind(rownames(indeed_df) , data.frame(indeed_df, row.names=NULL) ) # Recopy dataframe with index to help with ighraph formating
colnames(indeed_df)[1] <- "Node" # rename the previous index column as "Node"
indeed_df<-indeed_df[order(indeed_df$Activity_Score, decreasing=TRUE), ]
row.names(indeed_df) <- NULL # remove index repeat
result_list <-list(activity_score=indeed_df,diff_network=edge_dn)
return(result_list)
}
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