## ----message=FALSE, warning=FALSE---------------------------------------------------------------------------
library(dplyr)
library(ggplot2)
library(OmnipathR)
library(igraph)
library(ggraph)
library(magrittr)

## -----------------------------------------------------------------------------------------------------------
# Download protein-protein interactions
interactions <- omnipath() %>% 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()