## ----message=FALSE, warning=FALSE--------------------------------------------------------------------------- library(dplyr) library(ggplot2) library(OmnipathR) library(igraph) library(ggraph) library(magrittr) ## ----------------------------------------------------------------------------------------------------------- # Download protein-protein interactions interactions <- import_omnipath_interactions() %>% as_tibble() # Convert to igraph objects: OPI_g <- interaction_graph(interactions = interactions) ## ----eval=FALSE--------------------------------------------------------------------------------------------- # library(dbparser) # library(XML) # # ## parse data from XML and save it to memory # get_xml_db_rows("..path-to-DrugBank/full database.xml") # # ## load drugs data # drugs <- parse_drug() %>% select(primary_key, name) # drugs <- rename(drugs,drug_name = name) # # ## load drug target data # drug_targets <- # parse_drug_targets() %>% # select(id, name,organism,parent_key) %>% # rename(target_name = name) # # ## load polypeptide data # drug_peptides <- # parse_drug_targets_polypeptides() %>% # select( # id, # name, # general_function, # specific_function, # gene_name, # parent_id # ) %>% # rename(target_name = name, gene_id = id) # # # join the 3 datasets # drug_targets_full <- # inner_join( # drug_targets, # drug_peptides, # by = c("id" = "parent_id", "target_name") # ) %>% # inner_join(drugs, by = c("parent_key" = "primary_key")) %>% # select(-other_keys) ## ----------------------------------------------------------------------------------------------------------- drug_names = c( "Valproat" = "Valproic Acid", "Diclofenac" = "Diclofenac", "Paracetamol" = "Acetaminophen", "Ciproflaxin" = "Ciprofloxacin", "Nitrofurantoin" = "Nitrofurantoin", "Tolcapone", "Azathioprine", "Troglitazone", "Nefazodone", "Ketoconazole", "Omeprazole", "Phenytoin", "Amiodarone", "Cisplatin", "Cyclosporin A" = "Cyclosporine", "Verapamil", "Buspirone", "Melatonin", "N-Acetylcysteine" = "Acetylcysteine", "Vitamin C" = "Ascorbic acid", "Famotidine", "Vancomycin" ) ## ----eval=FALSE--------------------------------------------------------------------------------------------- # drug_target_data_sample <- # drug_targets_full %>% # filter(organism == "Humans", drug_name %in% drug_names) ## ----------------------------------------------------------------------------------------------------------- drug_targets <- OmnipathR:::drug_target_data_sample %>% filter(organism == "Humans", drug_name %in% drug_names) ## ----------------------------------------------------------------------------------------------------------- drug_targets %<>% select(-target_name, -organism) %>% mutate(in_OP = gene_id %in% c(interactions$source)) # not all drug-targets are in OP. print(all(drug_targets$in_OP)) # But each drug has at least one target in OP. drug_targets %>% group_by(drug_name) %>% summarise(any(in_OP)) ## ----------------------------------------------------------------------------------------------------------- POI <- tibble( protein = c( "NFE2L2", "HMOX1", "TP53", "CDKN1A", "BTG2", "NFKB1", "ICAM1", "HSPA5", "ATF4", "DDIT3", "XBP1" ) ) ## ----------------------------------------------------------------------------------------------------------- POI <- POI %>% mutate(in_OP = protein %in% interactions$target_genesymbol) # all POI is in Omnipath print(all(POI$in_OP)) ## ----------------------------------------------------------------------------------------------------------- source_nodes <- drug_targets %>% filter(in_OP, drug_name == "Cisplatin") %>% pull(gene_name) target_nodes <- POI %>% filter(in_OP) %>% pull(protein) collected_path_nodes <- list() for(i_source in 1:length(source_nodes)){ paths <- shortest_paths( OPI_g, from = source_nodes[[i_source]], to = target_nodes, output = "vpath" ) path_nodes <- lapply(paths$vpath, names) %>% unlist() %>% unique() collected_path_nodes[[i_source]] <- path_nodes } collected_path_nodes %<>% unlist %>% unique ## ----------------------------------------------------------------------------------------------------------- cisplatin_nodes <- c(source_nodes,target_nodes, collected_path_nodes) %>% unique() cisplatin_network <- induced_subgraph(graph = OPI_g, vids = cisplatin_nodes) ## ----------------------------------------------------------------------------------------------------------- V(cisplatin_network)$node_type <- ifelse( V(cisplatin_network)$name %in% source_nodes, "direct drug target", ifelse( V(cisplatin_network)$name %in% target_nodes, "POI", "intermediate node" ) ) # temporary fix against segfault that happens pre-4.4 R devel builds # only if the vignette is built within R CMD build and only on our # Ubuntu 22.04 machine # likely we can remove this conditional a few weeks later if (Sys.info()["user"] != "omnipath") { ggraph( cisplatin_network, layout = "lgl", area = vcount(cisplatin_network)^2.3, repulserad = vcount(cisplatin_network)^1.2, coolexp = 1.1 ) + geom_edge_link( aes( start_cap = label_rect(node1.name), end_cap = label_rect(node2.name)), arrow = arrow(length = unit(4, "mm") ), edge_width = .5, edge_alpha = .2 ) + geom_node_point() + geom_node_label(aes(label = name, color = node_type)) + scale_color_discrete( guide = guide_legend(title = "Node type") ) + theme_bw() + xlab("") + ylab("") + ggtitle("Cisplatin induced network") } ## ----sessionInfo, echo=FALSE-------------------------------------------------------------------------------- sessionInfo()