#' Add in edges to map documented in other pathways
#' @description For a specific pathway entity(gene), search KEGG databases
#' to see if it has any other documented relationships in KEGG.
#' expand_KEGG_edges
#' @export
#' @param entry_accession The Accession # of the pathway entity to 'keggerize'
#' @param KGML The KGML file of the current pathway
#' @param KEGG_mappings KEGG mappings for the current pathway
#' @param edges The expanded edges for the current pathway
#' @return A modified expanded edges data frame with additional rows for new
#' entries
#' @examples \dontrun{
#' KGML <- get_KGML("hsa04150")
#' KEGG_mappings <- expand_KEGG_mappings(KGML)
#' edges <- expand_KEGG_edges(KGML, KEGG_mappings)
#' entry_accession <- "2475"
#' mtor_plus_mtor <- keggerize_edges(entry_accession = entry_accession,
#' KGML = KGML,KEGG_mappings = KEGG_mappings,
#' edges = edges) }
#'
keggerize_edges <- function(entry_accession, KGML, KEGG_mappings, edges){
if(!"primary_pathway" %in% names(edges)){
edges$primary_pathwayID <- strsplit(KGML@pathwayInfo@name, ":")[[1]][2]
edges$primary_pathway <- KGML@pathwayInfo@title
}
entry_code <- paste0("hsa:",entry_accession)
entry_info <- keggGet(entry_code)
entry_pathways <- entry_info[[1]]["PATHWAY"]
entry_pathways <- names(entry_pathways$PATHWAY[1:length(unlist(entry_pathways))])
current_pathway <- strsplit(KGML@pathwayInfo@name, ":")[[1]][2]
entry_pathways <- entry_pathways[!entry_pathways %in% current_pathway]
for(p in 1:length(entry_pathways)){
pathway_KGML <- get_KGML(entry_pathways[p])
pathway_KEGG_mappings <- expand_KEGG_mappings(pathway_KGML)
pathway_edges <- expand_KEGG_edges(pathway_KGML, pathway_KEGG_mappings)
entry_edges <- pathway_edges[pathway_edges$entry1accession == entry_accession |
pathway_edges$entry2accession == entry_accession, ]
entry_sources <- entry_edges[entry_edges$entry1accession != entry_accession &
entry_edges$entry1accession %in% KEGG_mappings$entryACCESSION,]
entry_sources <- entry_sources[!duplicated(entry_sources[,6:16]),]
if(nrow(entry_sources) > 0){
for(i in 1:nrow(entry_sources)){
entry1_locations <- KEGG_mappings$entryID[KEGG_mappings$entrySYMBOL == entry_sources$entry1symbol[i]]
entry2_locations <- KEGG_mappings$entryID[KEGG_mappings$entrySYMBOL == entry_sources$entry2symbol[i]]
if(length(entry1_locations) > 1 | length(entry2_locations > 1)){
distance_matrix <- matrix(nrow = length(entry2_locations),
ncol = length(entry1_locations))
colnames(distance_matrix) <- entry1_locations
rownames(distance_matrix) <- entry2_locations
for(j in 1:nrow(distance_matrix)){
for (k in 1:ncol(distance_matrix)){
value <-
sqrt((KEGG_mappings$Xcoord[KEGG_mappings$entryID ==
colnames(distance_matrix)[k]][1]
- KEGG_mappings$Xcoord[KEGG_mappings$entryID ==
rownames(distance_matrix)[j]][1])^2
+ (KEGG_mappings$Ycoord[KEGG_mappings$entryID ==
colnames(distance_matrix)[k]][1]
- KEGG_mappings$Ycoord[KEGG_mappings$entryID ==
rownames(distance_matrix)[j]][1])^2)
# print(value)
distance_matrix[j,k] <- value
}
}
location <- which(distance_matrix == min(distance_matrix), arr.ind = TRUE)
entry_sources$entry1[i] <- colnames(distance_matrix)[location[1,2]]
entry_sources$entry2[i] <- rownames(distance_matrix)[location[1,1]]
}
if(length(entry1_locations) == 1 & length(entry2_locations) == 1){
entry_sources$entry1[i] <- entry1_locations
entry_sources$entry2[i] <- entry2_locations
}
}
}
entry_targets <- entry_edges[entry_edges$entry1accession == entry_accession &
entry_edges$entry2accession %in% KEGG_mappings$entryACCESSION,]
entry_targets <- entry_targets[!duplicated(entry_targets[,6:16]),]
if(nrow(entry_targets) > 0){
for(i in 1:nrow(entry_targets)){
entry1_locations <- KEGG_mappings$entryID[KEGG_mappings$entrySYMBOL == entry_targets$entry1symbol[i]]
entry2_locations <- KEGG_mappings$entryID[KEGG_mappings$entrySYMBOL == entry_targets$entry2symbol[i]]
if(length(entry1_locations) > 1 | length(entry2_locations > 1)){
distance_matrix <- matrix(nrow = length(entry2_locations),
ncol = length(entry1_locations))
colnames(distance_matrix) <- entry1_locations
rownames(distance_matrix) <- entry2_locations
for(j in 1:nrow(distance_matrix)){
for (k in 1:ncol(distance_matrix)){
value <-
sqrt((KEGG_mappings$Xcoord[KEGG_mappings$entryID ==
colnames(distance_matrix)[k]][1]
- KEGG_mappings$Xcoord[KEGG_mappings$entryID ==
rownames(distance_matrix)[j]][1])^2
+ (KEGG_mappings$Ycoord[KEGG_mappings$entryID ==
colnames(distance_matrix)[k]][1]
- KEGG_mappings$Ycoord[KEGG_mappings$entryID ==
rownames(distance_matrix)[j]][1])^2)
# print(value)
distance_matrix[j,k] <- value
}
}
location <- which(distance_matrix == min(distance_matrix), arr.ind = TRUE)
entry_targets$entry1[i] <- colnames(distance_matrix)[location[1,2]]
entry_targets$entry2[i] <- rownames(distance_matrix)[location[1,1]]
}
if(length(entry1_locations) == 1 & length(entry2_locations) == 1){
entry_targets$entry1[i] <- entry1_locations
entry_targets$entry2[i] <- entry2_locations
}
}
}
new_edges <- rbind(entry_sources, entry_targets)
if(nrow(new_edges) > 0) {
new_edges$primary_pathwayID <- strsplit(pathway_KGML@pathwayInfo@name, ":")[[1]][2]
new_edges$primary_pathway <- pathway_KGML@pathwayInfo@title
edges <- rbind(edges, new_edges)
}
print(p)
}
edges$edge_entry_ID <- paste0(edges$entry1, ":", edges$entry2)
edge_ID_sets <- edges$edge_entry_ID[!duplicated(edges$edge_entry_ID)]
edge_ID_mapper <- data.frame("edges" = edge_ID_sets,
edgeID = 1:length(edge_ID_sets),
stringsAsFactors = FALSE)
for(i in 1:nrow(edges)){
edges$edgeID[i] <- edge_ID_mapper$edgeID[match(edges$edge_entry_ID[i],
edge_ID_mapper$edges)]
}
edges <- edges[,names(edges) != "edge_entry_ID"]
return(edges)
}
# KGML <- get_KGML("hsa04150")
# KEGG_mappings <- expand_KEGG_mappings(KGML)
# edges <- expand_KEGG_edges(KGML, KEGG_mappings)
#
#
# keggerize_edges <- function(entry_accession, KGML, KEGG_mappings, edges){
# if(!"primary_pathway" %in% names(edges)){
# edges$primary_pathwayID <- strsplit(KGML@pathwayInfo@name, ":")[[1]][2]
# edges$primary_pathway <- KGML@pathwayInfo@title
# }
# entry_code <- paste0("hsa:",entry_accession)
# entry_info <- keggGet(entry_code)
# entry_pathways <- entry_info[[1]]["PATHWAY"]
# entry_pathways <- names(entry_pathways$PATHWAY[1:length(unlist(entry_pathways))])
# current_pathway <- strsplit(KGML@pathwayInfo@name, ":")[[1]][2]
# entry_pathways <- entry_pathways[!entry_pathways %in% current_pathway]
# for(i in 1:length(entry_pathways)){
# pathway_KGML <- get_KGML(entry_pathways[i])
# pathway_KEGG_mappings <- expand_KEGG_mappings(pathway_KGML)
# pathway_edges <- expand_KEGG_edges(pathway_KGML, pathway_KEGG_mappings)
# entry_edges <- pathway_edges[pathway_edges$entry1accession == entry_accession |
# pathway_edges$entry2accession == entry_accession, ]
# entry_sources <- entry_edges[entry_edges$entry1accession != entry_accession &
# entry_edges$entry1accession %in% KEGG_mappings$entryACCESSION,]
# # for(i in 1:nrow(entry_sources)){
# # entry1_locations <- KEGG_mappings$entryID[KEGG_mappings$entrySYMBOL == entry_sources$entry1symbol[i]]
# # entry2_locations <- KEGG_mappings$entryID[KEGG_mappings$entrySYMBOL == entry_sources$entry2symbol[i]]
# # distance_matrix <- matrix(nrow = length(entry2_locations),
# # ncol = length(entry1_locations))
# # colnames(distance_matrix) <- entry1_locations
# # rownames(distance_matrix) <- entry2_locations
# # for(j in 1:nrow(distance_matrix)){
# # for (k in 1:ncol(distance_matrix)){
# # value <-
# # sqrt((KEGG_mappings$Xcoord[KEGG_mappings$entryID ==
# # colnames(distance_matrix)[k]][1]
# # - KEGG_mappings$Xcoord[KEGG_mappings$entryID ==
# # rownames(distance_matrix)[j]][1])^2
# # + (KEGG_mappings$Ycoord[KEGG_mappings$entryID ==
# # colnames(distance_matrix)[k]][1]
# # - KEGG_mappings$Ycoord[KEGG_mappings$entryID ==
# # rownames(distance_matrix)[j]][1])^2)
# # print(value)
# # distance_matrix[j,k] <- value
# # }
# # }
# #
# #
# # }
# # for(i in 1:nrow(entry_sources)){
# # entry_sources$entry2[i] <- list(KEGG_mappings$entryID[KEGG_mappings$entrySYMBOL == entry_sources$entry2symbol[i]])
# # }
# # }
# entry_targets <- entry_edges[entry_edges$entry1accession == entry_accession &
# entry_edges$entry2accession %in% KEGG_mappings$entryACCESSION,]
# new_edges <- rbind(entry_sources, entry_targets)
# if(nrow(new_edges) > 0) {
# new_edges$primary_pathwayID <- strsplit(pathway_KGML@pathwayInfo@name, ":")[[1]][2]
# new_edges$primary_pathway <- pathway_KGML@pathwayInfo@title
#
# max_edge_ID <- max(edges$edgeID)
# for(j in 1:nrow(new_edges)){
# new_edges$edgeID[j] <- max_edge_ID + j
# }
# edges <- rbind(edges, new_edges)
# }
# print(i)
# }
# edges$edge_entry_ID <- paste0(edges$entry1, ":", edges$entry2)
# edge_ID_sets <- edges$edge_entry_ID[!duplicated(edges$edge_entry_ID)]
# edge_ID_mapper <- data.frame("edges" = edge_ID_sets,
# edgeID = 1:length(edge_ID_sets),
# stringsAsFactors = FALSE)
# for(i in 1:nrow(edges)){
# edges$edgeID[i] <- edge_ID_mapper$edgeID[match(edges$edge_entry_ID[i],
# edge_ID_mapper$edges)]
# }
# edges <- edges[,names(edges) != "edge_entry_ID"]
# return(edges)
# }
#
# mtor_plus_mtor <- keggerize_edges(entry_accession = entry_accession, KGML = KGML,
# KEGG_mappings = KEGG_mappings,
# edges = edges)
# #dim(edges)
# #[1] 581 16
# # dim(mtor_plus_mtor)
# # [1] 757 18
# mtor_plus_mtor_plus_deptor <- keggerize_edges(entry_accession = "64798", KGML = KGML,
# KEGG_mappings = KEGG_mappings,
# edges = mtor_plus_mtor)
#
#
#
#
#
# na_sources <- KEGG_gene_edges[is.na(KEGG_gene_edges$source),]
# na_targets<- KEGG_gene_edges[is.na(KEGG_gene_edges$target),]
# na_sources_and_targets <- KEGG_gene_edges[is.na(KEGG_gene_edges$target)& is.na(KEGG_gene_edges$source),]
#
# edges_complete_targets <- KEGG_gene_edges[!is.na(KEGG_gene_edges$target),]
# complete_edges <- edges_complete_targets[!is.na(edges_complete_targets$source),]
#
# # > dim(na_sources) + dim(na_targets) - dim(na_sources_and_targets)
# # [1] 2176 10
# #
# # > dim(KEGG_gene_edges) - dim(complete_edges)
# # [1] 2176 0
#
#
# for(j in 1:nrow(distance_matrix)){
# for (k in 1:ncol(distance_matrix)){
# distance_matrix[j,k] <
# sqrt((KEGG_mappings$Xcoord[KEGG_mappings$entryID ==
# colnames(distance_matrix)[1]][1]
# - KEGG_mappings$Xcoord[KEGG_mappings$entryID ==
# rownames(distance_matrix)[1]][1])^2
# + (KEGG_mappings$Ycoord[KEGG_mappings$entryID ==
# colnames(distance_matrix)[1]][1]
# - KEGG_mappings$Ycoord[KEGG_mappings$entryID ==
# rownames(distance_matrix)[1]][1])^2)
# }
# }
#
# KEGG_gene_edges <- complete_edges
# mtor_edges <- KEGG_gene_edges[KEGG_gene_edges$source == "MTOR" | KEGG_gene_edges$target == "MTOR",]
#
# unique_mtor_edges <- mtor_edges[!duplicated(mtor_edges),]
# mtor_edges_all_pathways <- unique_mtor_edges
#
# mtor_sources <- mtor_edges_all_pathways$source
# mtor_sources <- mtor_sources[!duplicated(mtor_sources)]
# # length(mtor_sources)
# # [1] 33
# mtor_targets <- mtor_edges_all_pathways$target
# mtor_targets <- mtor_targets[!duplicated(mtor_targets)]
# # length(mtor_targets)
# # [1] 26
#
# mtor_KGML <- get_KGML("hsa04150")
# mtor_KEGG_mappings <- expand_KEGG_mappings(mtor_KGML)
# mtor_edges <- expand_KEGG_edges(mtor_KGML, mtor_KEGG_mappings)
#
# sources_in_mtor_pathway <- mtor_KEGG_mappings[mtor_KEGG_mappings$entrySYMBOL %in% mtor_sources,]
# # dim(sources_in_mtor_pathway)
# # [1] 28 16
# targets_in_mtor_pathway <- mtor_KEGG_mappings[mtor_KEGG_mappings$entrySYMBOL %in% mtor_targets,]
# # dim(targets_in_mtor_pathway)
# # [1] 19 16
# internal_mtor_edges <- mtor_edges_all_pathways[mtor_edges_all_pathways$pathway_code == "path:hsa04150",]
