Implement first draft

.Rbuildignore

@@ -0,0 +1,4 @@
+^renv$
+^renv\.lock$
+^aNCA\.Rproj$
+^\.Rproj\.user$

.gitignore

@@ -0,0 +1,9 @@
+.Rproj.user
+.Rhistory
+.RData
+.Ruserdata
+aNCA.Rproj
+inst/guidelines
+inst/templates
+inst/shiny/data
+!inst/shiny/data/DummyRO_ADNCA.csv

.renvignore

@@ -0,0 +1,3 @@
+*
+!inst/shiny/*
+

DESCRIPTION

@@ -0,0 +1,53 @@
+Package: aNCA
+Title: (Pre-)clinical NCA in a dynamic shiny app.
+Version: 0.0.0.9000
+Authors@R: c(
+    person("Ercan", "Suekuer", , "[email protected]", role = c("aut", "cre"),
+           comment = c(ORCID = "0009-0001-1626-1526")),
+    person("Gerardo Jose", "Rodriguez", , "[email protected]", role = "aut",
+           comment = c(ORCID = "0000-0003-1413-0060")),
+    person("Pascal", "Baertschi", , "[email protected]", role = "aut",
+           comment = c(ORCID = "0000-0002-6533-0399")),
+    person("Jana", "Spinner", , "[email protected]", role = "aut",
+           comment = c(ORCID = "0009-0009-2197-9530")),
+    person("F. Hoffmann-La Roche AG", role = c("cph", "fnd"))
+  )
+Description: This application enables users to upload their datasets and
+    perform Non-Compartment Analysis (NCA) on both pre-clinical and
+    clinical datasets, with the results being easily visualizable. The NCA
+    can be tailored to calculate pharmacokinetic parameters for various
+    dosing regimens and time points, given certain restrictions. It also
+    features manual slope selection, simplifying the process of conducting
+    lambda-z-regression and PK-timepoint exclusions.  Furthermore, the
+    pharmacokinetic parameters can be dynamically visualized through
+    customized graphics such as line and mean plots. The calculated
+    pharmacokinetic parameters can be compiled in a dynamic table,
+    visualized using boxplots, or exported as a comprehensive report.
+    Designed with user-friendliness in mind, this app aims to make NCA
+    accessible and straightforward for all scientists. 
+License: MIT
+Imports: 
+    checkmate,
+    dplyr,
+    DT,
+    forcats,
+    ggplot2,
+    haven,
+    nestcolor,
+    PKNCA,
+    plotly,
+    rio,
+    rmarkdown,
+    shiny,
+    shinyBS,
+    shinyjqui,
+    shinyWidgets,
+    stats,
+    tern,
+    tidyr,
+    tools,
+    utils,
+    zip
+Encoding: UTF-8
+Roxygen: list(markdown = TRUE)
+RoxygenNote: 7.3.1

LICENSE

@@ -186,7 +186,7 @@
       same "printed page" as the copyright notice for easier
       identification within third-party archives.
 
-   Copyright [yyyy] [name of copyright owner]
+   Copyright 2024 Ercan Suekuer
 
    Licensed under the Apache License, Version 2.0 (the "License");
    you may not use this file except in compliance with the License.

NAMESPACE

@@ -0,0 +1,124 @@
+# Generated by roxygen2: do not edit by hand
+
+export(anonymize_pk_data)
+export(app_server)
+export(app_ui)
+export(apply_filters)
+export(as_factor_preserve_label)
+export(calculate_summary_stats)
+export(create_conc)
+export(create_dose)
+export(create_filter)
+export(flexible_violinboxplot)
+export(format_data)
+export(general_lineplot)
+export(general_meanplot)
+export(geometric.mean)
+export(has_label)
+export(lambda_slope_plot)
+export(pptestcd_dict)
+export(reshape_PKNCA_results)
+export(run_app)
+export(set_empty_label)
+import(checkmate)
+import(dplyr)
+import(forcats)
+import(ggplot2)
+import(haven)
+import(nestcolor)
+import(plotly)
+import(shiny)
+import(tidyr)
+importFrom(DT,DTOutput)
+importFrom(DT,datatable)
+importFrom(DT,formatStyle)
+importFrom(DT,renderDataTable)
+importFrom(DT,styleEqual)
+importFrom(PKNCA,PKNCA.options)
+importFrom(PKNCA,PKNCAconc)
+importFrom(PKNCA,PKNCAdata)
+importFrom(PKNCA,PKNCAdose)
+importFrom(PKNCA,pk.nca)
+importFrom(PKNCA,pknca_units_table)
+importFrom(dplyr,across)
+importFrom(dplyr,arrange)
+importFrom(dplyr,case_when)
+importFrom(dplyr,distinct)
+importFrom(dplyr,filter)
+importFrom(dplyr,group_by)
+importFrom(dplyr,left_join)
+importFrom(dplyr,mutate)
+importFrom(dplyr,pull)
+importFrom(dplyr,rename)
+importFrom(dplyr,rename_with)
+importFrom(dplyr,select)
+importFrom(dplyr,slice)
+importFrom(dplyr,summarise)
+importFrom(dplyr,ungroup)
+importFrom(dplyr,where)
+importFrom(ggplot2,aes)
+importFrom(ggplot2,facet_wrap)
+importFrom(ggplot2,geom_errorbar)
+importFrom(ggplot2,geom_line)
+importFrom(ggplot2,geom_point)
+importFrom(ggplot2,ggplot)
+importFrom(ggplot2,labs)
+importFrom(plotly,event_data)
+importFrom(plotly,plotlyOutput)
+importFrom(plotly,plotly_build)
+importFrom(plotly,renderPlotly)
+importFrom(rio,export_list)
+importFrom(rmarkdown,render)
+importFrom(shiny,actionButton)
+importFrom(shiny,checkboxInput)
+importFrom(shiny,column)
+importFrom(shiny,conditionalPanel)
+importFrom(shiny,downloadButton)
+importFrom(shiny,fileInput)
+importFrom(shiny,fluidPage)
+importFrom(shiny,fluidRow)
+importFrom(shiny,helpText)
+importFrom(shiny,icon)
+importFrom(shiny,insertUI)
+importFrom(shiny,mainPanel)
+importFrom(shiny,modalButton)
+importFrom(shiny,modalDialog)
+importFrom(shiny,navbarPage)
+importFrom(shiny,numericInput)
+importFrom(shiny,observeEvent)
+importFrom(shiny,plotOutput)
+importFrom(shiny,radioButtons)
+importFrom(shiny,reactiveVal)
+importFrom(shiny,reactiveValues)
+importFrom(shiny,removeUI)
+importFrom(shiny,renderUI)
+importFrom(shiny,req)
+importFrom(shiny,selectInput)
+importFrom(shiny,showModal)
+importFrom(shiny,sidebarLayout)
+importFrom(shiny,sidebarPanel)
+importFrom(shiny,tabPanel)
+importFrom(shiny,tags)
+importFrom(shiny,textInput)
+importFrom(shiny,uiOutput)
+importFrom(shiny,updateCheckboxInput)
+importFrom(shiny,updateNavbarPage)
+importFrom(shiny,updateNumericInput)
+importFrom(shiny,updateSelectInput)
+importFrom(shiny,updateTabsetPanel)
+importFrom(shinyBS,bsModal)
+importFrom(shinyFiles,shinyDirChoose)
+importFrom(shinyWidgets,dropdown)
+importFrom(shinyWidgets,pickerInput)
+importFrom(shinyWidgets,switchInput)
+importFrom(shinyWidgets,updatePickerInput)
+importFrom(shinyjqui,orderInput)
+importFrom(shinyjqui,updateOrderInput)
+importFrom(stats,sd)
+importFrom(tern,g_ipp)
+importFrom(tidyr,pivot_longer)
+importFrom(tidyr,pivot_wider)
+importFrom(tools,file_ext)
+importFrom(utils,read.csv)
+importFrom(utils,write.csv)
+importFrom(zip,zipr)

R/anonymize_pk_data.R

@@ -0,0 +1,166 @@
+#' This function anonymizes RO numbers and Study IDs of pk data files.
+#' 
+#' @import haven
+#' @import dplyr
+#' @import checkmate
+#' 
+#' @param path path to dataframe in xpt, sas or csv format
+#' @param overwrite decides whether file at input location `path` is overwritten. default is TRUE
+#' 
+#' @return anonymized dataframe file
+#' 
+#' @export
+#' 
+#' 
+#'@author Pascal Bärtschi
+#' 
+
+anonymize_pk_data <- function(path, 
+                              drug_map = NULL,
+                              overwrite = TRUE){
+
+  # assert file
+  checkmate::assert_file_exists(path)
+  # if (!is.null(drug_map)){
+  #   # check named vector
+  #   # checkmate::assert(checkNamed(drug_map))
+  #   # # assert names of drug dict somewhere in values of dataframe (with regex)
+  #   # drug_regex <- paste(names(drug_map), collapse = "|")
+  #   # checkmate::assert(any(grep(drug_regex, strings)))
+  # }
+
+
+  # file extension
+  extension <- str_split_i(path, "\\.", i = -1)
+
+  # extension decision read-in
+  if (extension == "csv"){
+    data <- read.csv(path)
+  } else if (extension == "sas7bdat"){
+    data <- read_sas(path)
+  } else if (extension == "xpt"){
+    data <- read_xpt(path)
+  } else {
+    stop("This file extension is not supported yet.")
+  }
+
+  #assert data loading
+  checkmate::assert(checkDataFrame(data))
+
+  # find all ronumbers
+  all_ronum <- lapply(X = data, FUN = function(x) str_extract(x, "\\bRO\\d{7}\\b")) %>% 
+    unlist() %>%
+    unique() %>%
+    na.omit()
+
+  # find all tracknumbers
+  all_tracknum <- lapply(X = data, FUN = function(x) str_extract(x, "\\bTrack\\d{2}\\b")) %>% 
+    unlist() %>%
+    unique() %>%
+    na.omit()
+
+  all_studyid <- lapply(X = data, FUN = function(x) str_extract(x, "\\b..\\d{5}\\b")) %>% 
+    unlist() %>%
+    unique() %>%
+    na.omit()
+
+  if (length(all_ronum) > 0){
+    # instead of seq along, generate random numbers with 7 digits
+    ronum_map <- setNames(paste0("Analyte", sprintf("%02d", seq_along(all_ronum))),
+                          all_ronum)
+  } else {
+    ronum_map <- character(0)
+  }
+
+  if (length(all_tracknum) > 0){
+    # instead of seq along, generate random numbers with 7 digits
+    tracknum_map <- setNames(paste0("Analyte",  sprintf("%02d", seq_along(all_tracknum))),
+                          all_tracknum)
+  } else {
+    tracknum_map <- character(0)
+  }
+
+  if (length(all_studyid) > 0){
+    studyid_map <- setNames(paste0("XX",  sprintf("%02d", seq_along(all_studyid))),
+                            all_studyid)
+  } else {
+    studyid_map <- character(0)
+  }
+
+
+
+  # checkmate::assert(checkVector(ronum_map, min.len = 1), 
+  #                   checkVector(studyid_map, min.len = 1), 
+  #                   combine = "and")
+
+  # concatenate the maps
+  concat_map <- c(ronum_map, studyid_map, tracknum_map, drug_map)
+
+  # function to replace according to the map
+  replace_str_with_map <- function(x, map) {
+    for (str_ in names(map)) {
+      x <- gsub(str_, map[[str_]], x)
+    }
+    return(x)
+  }
+
+  # columns required for NCA
+  req4nca <- c("STUDYID", "USUBJID", "ANALYTE", "PCSPEC", "DOSEFRQ", 'DOSNO', "AFRLT", "ARRLT", "NRRLT", "NFRLT", "PCSTRESC", "PARAM", "TAU",
+               "PCSTRESU", "ROUTE", "DOSEA", "AGE", "SEX", "RACE", "ADOSEDUR", 'DOSEDURU', "NDOSEDUR", "RRLTU", "DOSEA", "DOSEU", "PCLLOQ", "DRUG",
+               "AVISIT", "AVAL", "AVALU", "DOSEU", "EVID", "ATPTREF", "SITEID", "TRT01A", "TRT01P", "PCRFTDTM", "WTBL", "WTBLU", "HTBL", "HTBLU")
+
+  # mutate and rename
+  data <- data %>% 
+    # apply the map to all columns that hold RO and STUDYNUMBERS
+    mutate_all(~replace_str_with_map(., concat_map)) %>% 
+    rename_with(~replace_str_with_map(., concat_map)) %>% 
+    # select only columns that are needed to perform NCA
+    select(any_of(req4nca))
+
+  # find the req4nca columns that are not in data
+  if (setdiff(req4nca, colnames(data)) %>% length > 0){
+    message(paste("The dataframe with path", path, 
+                  "is missing the following colnames: ", 
+                  paste(setdiff(req4nca, colnames(data)), collapse = ", ")))
+  }
+
+  # compose a message warning that the unique values of start_with("TRT") are ... and that DRUG names have to anonymized by hand
+  if (any(grepl("TRT", colnames(data)))){
+    message(paste("The unique values of the columns starting with TRT are: ", data %>% 
+                  select(all_of(data %>% 
+                                select(starts_with("TRT")) %>% 
+                                colnames(.))) %>% 
+                  unique() %>% 
+                  paste(., collapse = ", "), toupper(". Please make sure to replace drugnames!")))
+
+  }
+
+
+  # save the file
+  if (extension == "csv"){
+    if (overwrite){
+      write.csv(data, path, row.names = F)
+    } else {
+      write.csv(data, paste0(gsub(".csv", "", path), "_anonymized.csv"), row.names = F)
+    }
+  } else if (extension == "sas7bdat"){
+    if (overwrite){
+      write_xpt(data, gsub(".sas7bdat", ".xpt", path))
+      file.remove(path)
+      message("The sas7bdat file was converted to xpt and the original file was removed, as the sas7bdat format was deprecated in haven.")
+    } else {
+      write_xpt(data, paste0(gsub(".sas7bdat", "", path), "_anonymized.xpt"))
+      file.remove(path)
+      message("The sas7bdat file was converted to xpt and the original file was removed, as the sas7bdat format was deprecated in haven.")
+    }
+  } else if (extension == "xpt"){
+    if (overwrite){
+      write_xpt(data, path)
+    } else {
+      write_xpt(data, paste0(gsub(".xpt", "", path), "_anonymized.xpt"))
+    }
+  }
+
+}
+#*~*#
+

R/app_server.R

@@ -0,0 +1,22 @@
+#' Server function for the Shiny app
+#'
+#' @import shiny
+#' @importFrom shiny observeEvent reactiveVal reactiveValues insertUI removeUI updateSelectInput updateNavbarPage updateTabsetPanel updateCheckboxInput updateNumericInput showModal modalDialog textInput actionButton modalButton numericInput renderUI req
+#' @importFrom dplyr mutate filter select group_by summarise pull arrange ungroup rename_with across case_when left_join rename
+#' @importFrom tools file_ext
+#' @importFrom DT renderDataTable datatable formatStyle styleEqual
+#' @importFrom PKNCA PKNCAconc PKNCAdose PKNCAdata pk.nca PKNCA.options pknca_units_table
+#' @importFrom utils read.csv write.csv
+#' @importFrom plotly renderPlotly plotlyOutput plotly_build event_data
+#' @importFrom shinyWidgets pickerInput switchInput updatePickerInput
+#' @importFrom shinyjqui orderInput
+#' @importFrom ggplot2 ggplot geom_errorbar geom_point geom_line labs aes facet_wrap
+#' @importFrom zip zipr
+#' @importFrom rio export_list
+#' @importFrom rmarkdown render
+#' @importFrom shinyFiles shinyDirChoose
+#'
+#' @export
+app_server <- function(input, output, session) {
+  source(system.file("shiny/server.R", package = "aNCA"), local = TRUE)$value(input, output, session)
+}