more refined classification

DESCRIPTION

@@ -2,7 +2,7 @@ Package: pharmOncoX
 Type: Package
 Title: Molecularly targeted cancer drugs and biomarkers
 Version: 1.5.0
-Date: 2024-01-25
+Date: 2024-01-28
 Authors@R: 
     c(person(given = "Sigve",
              family = "Nakken",

NEWS.md

@@ -1,3 +1,7 @@
+# Version 1.5.1 (January 28th 2024)
+
+* Refine possible values in `treatment_category` argument to `get_drugs()` function
+
 # Version 1.5.0 (January 25th 2024)
 
 * Considerable improvement of drug classifications (output column `atc_level3`),

R/helpers.R

@@ -9,7 +9,9 @@ get_targeted_drugs <- function(cache_dir = NA) {
 
 
   onco_drugs <- 
-    get_drugs(treatment_category = c("targeted_therapy"),
+    get_drugs(treatment_category = c("targeted_therapy_classified",
+                                     "targeted_therapy_unclassified",
+                                     "hormone_therapy_classified"),
               cache_dir = cache_dir,
               drug_classified_cancer = TRUE,
               drug_cancer_indication = TRUE,

R/pharm_oncox.R

@@ -14,7 +14,10 @@
 #' data exists in cache
 #' @param exclude_salt_forms exclude salt forms of drugs
 #' @param exclude_adc exclude antibody-drug conjugates (ADCs)
-#' @param treatment_category treatment category ('targeted_therapy','chemo_therapy','hormone_therapy')
+#' @param treatment_category main treatment category, classified according to 
+#' ATC or not ('targeted_therapy_classified',
+#' 'targeted_therapy_unclassified','chemo_therapy_classified','hormone_therapy_classified',
+#' 'immuno_suppressants_classified','other')
 #' @param drug_is_approved logical indicating if resulting drug records 
 #' should contain approved drugs only
 #' @param drug_target character vector with drug targets (gene symbols) 
@@ -125,7 +128,12 @@ get_drugs <- function(
     exclude_salt_forms = TRUE,
     exclude_adc = FALSE,
     treatment_category = 
-      c("targeted_therapy","chemo_therapy","hormone_therapy"),
+      c("targeted_therapy_classified",
+        "targeted_therapy_unclassified",
+        "chemo_therapy_classified",
+        "hormone_therapy_classified",
+        "immuno_suppressants_classified",
+        "other"),
     drug_is_approved = FALSE,
     drug_target = NULL,
     drug_action_type = NULL,
@@ -149,9 +157,12 @@ get_drugs <- function(
       "drug2target2indication")
 
   valid_treatment_categories <- 
-    c("hormone_therapy",
-      "targeted_therapy",
-      "chemo_therapy")
+    c("hormone_therapy_classified",
+      "targeted_therapy_classified",
+      "targeted_therapy_unclassified",
+      "chemo_therapy_classified",
+      "immuno_suppressants_classified",
+      "other")
 
   is_valid_treatment_category <- 
     unique(treatment_category %in% valid_treatment_categories)
@@ -337,39 +348,34 @@ get_drugs <- function(
 
 
   ## targeted + chemo + hormone
-  treatment_category_regex <- "(_targeted|hormone|chemo)_therapy$"
+  treatment_category_regex <- ""
+  atc_treatment_strings <- c()
 
-  if("hormone_therapy" %in% treatment_category & 
-     !("chemo_therapy" %in% treatment_category) & 
-      !("targeted_therapy" %in% treatment_category)){
-    treatment_category_regex <- "_hormone_therapy$"
+  if("hormone_therapy_classified" %in% treatment_category){
+    atc_treatment_strings <- c(atc_treatment_strings, "cancer_hormone_therapy")
   }
-  if("hormone_therapy" %in% treatment_category & 
-     "chemo_therapy" %in% treatment_category & 
-     !("targeted_therapy" %in% treatment_category)){
-    treatment_category_regex <- "_(hormone|chemo)_therapy$"
+  if("chemo_therapy_classified" %in% treatment_category){
+    atc_treatment_strings <- c(atc_treatment_strings, "cancer_chemo_therapy")
   }
-  if("targeted_therapy" %in% treatment_category & 
-     !("chemo_therapy" %in% treatment_category) & 
-     !("hormone_therapy" %in% treatment_category)){
-    treatment_category_regex <- "_targeted_therapy$"
+  if("targeted_therapy_classified" %in% treatment_category){
+    atc_treatment_strings <- c(atc_treatment_strings, "cancer(_adc)?_targeted_therapy")
   }
-  if("chemo_therapy" %in% treatment_category & 
-     !("targeted_therapy" %in% treatment_category) & 
-     !("hormone_therapy" %in% treatment_category)){
-    treatment_category_regex <- "_chemo_therapy$"
+  if("targeted_therapy_unclassified" %in% treatment_category){
+    atc_treatment_strings <- c(atc_treatment_strings, "cancer_unclassified")
   }
-  if("targeted_therapy" %in% treatment_category & 
-     "chemo_therapy" %in% treatment_category & 
-     !("hormone_therapy" %in% treatment_category)){
-    treatment_category_regex <- "_(targeted|chemo)_therapy$"
+  if("immuno_suppressants_classified" %in% treatment_category){
+    atc_treatment_strings <- c(atc_treatment_strings, "cancer_immuno_suppressants")
   }
-  if("targeted_therapy" %in% treatment_category & 
-     "hormone_therapy" %in% treatment_category & 
-     !("chemo_therapy" %in% treatment_category)){
-    treatment_category_regex <- "_(targeted|hormone)_therapy$"
+  if("other" %in% treatment_category){
+    atc_treatment_strings <- c(atc_treatment_strings, "(other_targeted_therapy|unknown)")
   }
 
+  treatment_category_regex <- paste0(
+    "^(", paste(atc_treatment_strings, collapse="|"), ")$")
+
+  #cat(paste0('Treatment category regex: ', treatment_category_regex))
+  #cat('\n')
+
   drug_records <- drug_records |>
     dplyr::filter(
       !is.na(.data$atc_treatment_category) &

data-raw/biomarker_utilities.R

@@ -430,7 +430,7 @@ expand_hgvs_terms <- function(var, aa_dict, add_codon_markers = FALSE) {
 }
 
 load_civic_biomarkers <- function(
-    datestamp = '20230518',
+    datestamp = '20240114',
     compound_synonyms = NULL,
     hg38_fasta = 
       "/Users/sigven/research/DB/hg38/hg38.fa",
@@ -2059,6 +2059,8 @@ map_biomarker_phenotypes <- function(biomarkers_clinical = NULL,
       is.na(primary_site) & stringr::str_detect(do_name,"prostate") ~ "Prostate",
       is.na(primary_site) & stringr::str_detect(do_name,"pancrea") ~ "Pancreas",
       is.na(primary_site) & stringr::str_detect(do_name,"lung") ~ "Lung",
+      is.na(primary_site) & stringr::str_detect(do_name,"myeloid") ~ "Myeloid",
+      is.na(primary_site) & stringr::str_detect(do_name,"lymphoma") ~ "Lymphoid",
       is.na(primary_site) & stringr::str_detect(do_name,"ovary|ovarian") ~ "Ovary",
       TRUE ~ as.character(primary_site)
     ))

data-raw/drug_utilities.R

@@ -2643,6 +2643,15 @@ assign_drug_category <- function(drug_df = NULL,
         stringr::str_detect(
           atc_code_level3, "(\\|L01XX[A-J])|(^L01XX[A-J])"
         ) ~ "cancer_targeted_therapy",
+      !is.na(target_symbol) &
+        !is.na(atc_code_level3) &
+        stringr::str_detect(
+          atc_code_level3, "(\\|L04)|(^L04)"
+        ) ~ "cancer_immuno_suppressants",
+      !is.na(target_symbol) &
+        stringr::str_detect(drug_cancer_relevance,"^by_cancer") & 
+        (is.na(atc_code_level3) | atc_code_level3 == "NA")
+         ~ "cancer_unclassified",
       !is.na(target_symbol) &
       !is.na(atc_code_level3) &
         stringr::str_detect(

pkgdown/index.md

@@ -8,14 +8,14 @@ The data is largely based on drug-target-indication associations provided by the
 
 Drug-target associations from the Open Targets Platform have furthermore been integrated and appended with drug information from [NCI Thesaurus](https://ncithesaurus.nci.nih.gov/ncitbrowser/), showing also non-targeted cancer drugs (chemotherapeutic agents etc.), and various drug regimens.
 
-We provide anti-cancer drugs in **pharmOncoX** with drug class labeling from [Anatomical Therapeutic Chemical (ATC) Classification System](https://www.whocc.no/atc_ddd_index/), enabling a filtering of drugs according to their main mechanisms of action.
+_pharmOncoX_ provides anti-cancer drug classification through existing entries in the [Anatomical Therapeutic Chemical (ATC) Classification System](https://www.whocc.no/atc_ddd_index/), and these have been extended significantly with manual curation, also by establishing novel drug categories that are presently missing in the ATC classificiation tree (examples include _AURK inhibitors_, _MET inhibitors_, _BET inhibitors_, _AKT inhibitors_, _PLK inhibitors_, _IAP inhibitors_ etc.) enabling a filtering of drugs according to their main mechanisms of action.
 
-Currently (as of late October 2023), `pharmOncoX` is built upon the following 
+Currently (as of late Janurary 2024), `pharmOncoX` is built upon the following 
 releases of external databases:
 
- - Open Targets Platform (2023.09)
+ - Open Targets Platform (2023.12)
  - ChEMBL (v33)
- - NCI Thesaurus (23.09d)
+ - NCI Thesaurus (23.12d)
 
 ### Getting started
 

vignettes/pharmOncoX.Rmd

@@ -45,13 +45,13 @@ cache_dir <- tempdir()
 ## Targeted agents
 
 * Plotted below are key statistics with respect to drug classification
-numbers for targeted and chemotherapy agents found in _pharmOncoX_. Existing classifications have been retrieved from [ATC](https://www.whocc.no/), and these have been extended with manual addition/curation, and also establishing new levels in the ATC tree. Note that only drugs that are indicated for cancer conditions (as harvested from the Open Targets platform) are considered in the numbers plotted below.
+numbers for targeted and chemotherapy agents found in _pharmOncoX_. Existing drug classifications have been retrieved from [ATC](https://www.whocc.no/), and these have been extended with manual addition/curation, and also through the establishment of multiple novel levels in the ATC tree, particularly for targeted therapies. Note that only drugs that are indicated for cancer conditions (as harvested from the Open Targets platform) are considered in the numbers plotted below.
 
 ```{r targeted_agents, echo = F, eval = T, results="hide"}
 
 drugs <- get_drugs(
   cache_dir = cache_dir,
-  treatment_category =  c("targeted_therapy"),
+  treatment_category =  c("targeted_therapy_classified"),
   output_resolution = "drug",
 	drug_action_inhibition = T, drug_source_opentargets = T)
 
@@ -101,7 +101,7 @@ p_targeted_classifications
 
 drugs <- get_drugs(
   cache_dir = cache_dir,
-  treatment_category =  c("chemo_therapy"),
+  treatment_category =  c("chemo_therapy_classified"),
   output_resolution = "drug",
 	drug_source_opentargets = T)
 
@@ -157,7 +157,8 @@ p_chemo_classifications
 
 drugs <- get_drugs(
   cache_dir = cache_dir,
-  treatment_category =  c("targeted_therapy"),
+  treatment_category =  c("targeted_therapy_classified",
+                          "targeted_therapy_unclassified"),
 	drug_target = c('BRAF'))
 
 ## Number of drug records
@@ -177,7 +178,7 @@ colnames(drugs$records)
 
 drugs <- get_drugs(
   cache_dir = cache_dir, 
-  treatment_category =  c("targeted_therapy"),
+  treatment_category =  c("targeted_therapy_classified"),
   drug_action_inhibition = T,
   output_resolution = "drug2target")$records |>
   dplyr::filter(atc_level3 == "RAS inhibitors")
@@ -218,7 +219,7 @@ dt_drugtable_ras_inhibitors
 
 drugs <- get_drugs(
   cache_dir = cache_dir, 
-  treatment_category =  c("targeted_therapy"),
+  treatment_category =  c("targeted_therapy_classified"),
   drug_action_inhibition = T,
   drug_source_opentargets = T, 
   output_resolution = "drug" )$records |>
@@ -260,7 +261,7 @@ dt_drugtable_mek_inhibitors
 
 drugs <- get_drugs(
   cache_dir = cache_dir, 
-  treatment_category =  c("targeted_therapy"),
+  treatment_category =  c("targeted_therapy_classified"),
   drug_source_opentargets = F,
   drug_classified_cancer = T,
    output_resolution = "drug2target")
@@ -314,6 +315,7 @@ dt_drugtable_ici
 drugs <- get_drugs(
   cache_dir = cache_dir, 
   output_resolution = "drug2target", 
+  treatment_category = c("targeted_therapy_classified"),
   drug_source_opentargets = T,
   drug_indication_main = "Lung")
 
@@ -366,7 +368,7 @@ dt_drugtable_ici_lung
 
 drugs <- get_drugs(
   cache_dir = cache_dir, 
-  treatment_category = c("chemo_therapy"),
+  treatment_category = c("chemo_therapy_classified"),
   output_resolution = "drug")
 
 drugs$records <- drugs$records |>
@@ -411,6 +413,7 @@ dt_drugtable_metabolites
 
 drugs <- get_drugs(
   cache_dir = cache_dir, 
+  treatment_category = "chemo_therapy_classified",
   output_resolution = "drug")
 
 drugs$records <- drugs$records |>
@@ -454,6 +457,7 @@ dt_drugtable_taxanes
 
 drugs <- get_drugs(
   cache_dir = cache_dir, 
+  treatment_category = "chemo_therapy_classified",
   output_resolution = "drug")
 
 drugs$records <- drugs$records |>
@@ -495,7 +499,7 @@ dt_drugtable_platins
 
 ## Reported associations between BRCA1/2 alterations and drug sensitivity
 
-Get evidence from [CIViC](https://civicdb.org) and [CGI](https://www.cancergenomeinterpreter.org/biomarkers) for cancer drug sensitivity of BRCA1/2 alterations (somatically (tumor) or inherited/germline)
+* Get evidence from [CIViC](https://civicdb.org) and [CGI](https://www.cancergenomeinterpreter.org/biomarkers) for cancer drug sensitivity of BRCA1/2 alterations (somatically (tumor) or inherited/germline)
 
 ```{r biomarkers, echo = T}