Merge branch 'repo_update' into 'master'

add drug targets and update various files: See merge request !268

Merge branch 'repo_update' into 'master'
add drug targets and update various files: See merge request !268
1eccba28 · Marek Ostaszewski · eacdd016 · f4ad0fab · 1eccba28 · 1eccba28
Commit 1eccba28 authored Jan 26, 2021 by Marek Ostaszewski
--- a/Curation/ER Stress/ER_Stress_stable.pdf
+++ b/Curation/ER Stress/ER_Stress_stable.pdf
--- a/Curation/SARS-CoV-2 proteins/Orf3b/Orf3b_0620_2020.xml
+++ b/Curation/SARS-CoV-2 proteins/Orf3b/Orf3b_0620_2020.xml
@@ -399,6 +399,14 @@
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 </celldesigner:listOfComplexSpeciesAliases>
 <celldesigner:listOfSpeciesAliases>
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+<celldesigner:speciesAlias id="sa4" species="s7" compartmentAlias="ca5">
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@@ -587,11 +596,10 @@
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@@ -1253,11 +1261,7 @@
 <celldesigner:protein id="pr23" name="TCRβ" type="GENERIC"/>
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-</celldesigner:listOfRegions>
-</celldesigner:gene>
+<celldesigner:gene id="gn1" name="IFNB1" type="GENE"/>
 </celldesigner:listOfGenes>
 <celldesigner:listOfRNAs>
 <celldesigner:RNA id="rn1" name="IFNB1" type="RNA"/>
@@ -1322,9 +1326,16 @@
 </celldesigner:extension>
 </annotation>
 </compartment>
+<compartment metaid="c5" id="c5" name="nucleus" size="1" units="volume" outside="default">
+<annotation>
+<celldesigner:extension>
+<celldesigner:name>nucleus</celldesigner:name>
+</celldesigner:extension>
+</annotation>
+</compartment>
 </listOfCompartments>
 <listOfSpecies>
-<species metaid="s1" id="s1" name="Orf3b" compartment="default" initialAmount="0" charge="0">
+<species metaid="s1" id="s1" name="Orf3b" compartment="c5" initialAmount="0" charge="0">
 <annotation>
 <celldesigner:extension>
 <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
@@ -1332,10 +1343,13 @@
 <celldesigner:class>PROTEIN</celldesigner:class>
 <celldesigner:proteinReference>pr1</celldesigner:proteinReference>
 </celldesigner:speciesIdentity>
+<celldesigner:listOfCatalyzedReactions>
+<celldesigner:catalyzed reaction="re5"/>
+</celldesigner:listOfCatalyzedReactions>
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 </annotation>
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-<species metaid="s7" id="s7" name="IFNB1" compartment="default" initialAmount="0" charge="0">
+<species metaid="s7" id="s7" name="IFNB1" compartment="c5" initialAmount="0" charge="0">
 <annotation>
 <celldesigner:extension>
 <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
@@ -1742,54 +1756,6 @@
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@@ -1826,6 +1805,15 @@
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+<celldesigner:alias>sa1</celldesigner:alias>
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-<celldesigner:baseReactant species="s22" alias="sa38">
-<celldesigner:linkAnchor position="INACTIVE"/>
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 <celldesigner:baseProducts>
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-<celldesigner:baseReactant species="s72" alias="sa34">
-<celldesigner:linkAnchor position="INACTIVE"/>
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 <celldesigner:baseReactant species="s55" alias="csa11">
 <celldesigner:linkAnchor position="ENE"/>
 </celldesigner:baseReactant>
@@ -2395,14 +2377,14 @@
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-<speciesReference metaid="CDMT00003" species="s72">
+<speciesReference metaid="CDMT00004" species="s72">
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 </annotation>
 </speciesReference>
-<speciesReference metaid="CDMT00004" species="s55">
+<speciesReference metaid="CDMT00005" species="s55">
 <annotation>
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--- a/Integration/MINERVA_access/get_drug_targets.R
+++ b/Integration/MINERVA_access/get_drug_targets.R
@@ -6,7 +6,7 @@
 ##################################################

 ### Helper functions to access and retrieve content from MINERVA-hosted diagrams
-source("minerva_access_functions.R")
+source("https://git-r3lab.uni.lu/covid/models/-/raw/master/Integration/MINERVA_access/minerva_access_functions.R")

 ### The address of the COVID-19 Disease Map in MINERVA
 map <- "https://covid19map.elixir-luxembourg.org/minerva/api/"
@@ -18,5 +18,44 @@ refs <- lapply(map_components$map_elements, function(x) data.frame(id = x$id,
                                                                   uniprot = get_annotation(x$references, "UNIPROT")))
 names(refs) <- map_components$models$name

+### A helper function to retrieve one (first) element alias for all unique UniProts.
+### The drug search API call is based on the alias of an element in the MINERVA project,
+### while the drug targets are HGNC/UniProt based. Multiple aliases can point to the
+### same HGNC/UniProt. To optimise drug requests, we take only one alias for
+### each unique UniProt in a given diagram.
+unique_drugs <- function(funiprot_references) {
+  frefs <- funiprot_references[!is.na(funiprot_references[,"uniprot"]),]
+  if(nrow(frefs) == 0) { return(NULL) }
+  sapply(unique(frefs[,"uniprot"]), function(x) frefs[x == frefs[,"uniprot"],1][1])
+}
+
+### Get the UniProt-alias mappings using the helper function
+upd <- sapply(refs, unique_drugs)
+
+### Get the id of the default project
+map_project <- paste0(map,"projects/",get_default_project(map),"/")
+
+### Lengthy calculation, ask for drug targets of all unique UniProt ids in every pathway
+all_drugs <- c()
+### For each pathway
+for(u in 1:length(upd)) {
+  if(!is.null(upd[[u]])) {
+    message(paste0("Processing diagram: ", map_components$models$name[u]))
+    ### For each UniProt id
+    for(p in 1:length(upd[[u]])) {
+      ### Add a row to the global table with pathway name, UniProt id and the drugs 
+      ### targeting the element alias associated with this UniProt
+      all_drugs <- rbind(all_drugs,
+                         c(pathway_name = map_components$models$name[u],
+                           uniprot = names(upd[[u]])[p],
+                           drugs = paste(fromJSON(ask_GET(paste0(map_project,"drugs:search?target=ALIAS:", upd[[u]][p])))$name,
+                                         collapse = ";")))
+    }
+  }
+}
+
+### Write down the table
+write.table(all_drugs, file = "MINERVA_C19DM_drugs.tsv", sep = "\t", quote = F, col.names = T, row.names = F)
+
 message("Done.")

--- a/Resources/Crosstalks/C19DM_crosstalks_focused.cys
+++ b/Resources/Crosstalks/C19DM_crosstalks_focused.cys
--- a/Resources/Crosstalks/find_crosstalks.R
+++ b/Resources/Crosstalks/find_crosstalks.R
@@ -6,7 +6,7 @@
 ##################################################

 ### Helper functions to access and retrieve content from MINERVA-hosted diagrams
-source("minerva_access.R")
+source("https://git-r3lab.uni.lu/covid/models/-/raw/master/Integration/MINERVA_access/minerva_access_functions.R")
 ### For handling WikiPathway queries
 library(rWikiPathways)