#------------------------------------------------------------------------------#
 # Exported/Internal variables
 #------------------------------------------------------------------------------#
 

 # Internal: default mandatory IS vars and associated column types.
 # The combination of these fields defines a unique integration site.
 .default_mandatory_IS_vars <- function() {

     tibble::tribble(
         ~names, ~types, ~transform, ~flag, ~tag,
         "chr", "char", NULL, "required", "chromosome",
         "integration_locus", "int", NULL, "required", "locus",
         "strand", "char", NULL, "required", "is_strand"
     )

 }
 

 # Internal: default genomic annotation IS vars and associated column types.
 .default_annotation_IS_vars <- function() {

     tibble::tribble(
         ~names, ~types, ~transform, ~flag, ~tag,
         "GeneName", "char", NULL, "required", "gene_symbol",
         "GeneStrand", "char", NULL, "required", "gene_strand"
     )

 }
 

 # Internal: default association file columns and types
 .default_af_cols <- function() {

     tibble::tribble(
         ~names, ~types, ~transform, ~flag, ~tag,
         "ProjectID", "char", NULL, "required", "project_id",
         "FUSIONID", "char", NULL, "optional", "fusion_id",
         "PoolID", "char", NULL, "required", "pool_id",
         "TagSequence", "char", NULL, "required", "tag_seq",
         "SubjectID", "char", NULL, "required", "subject",
         "VectorType", "char", NULL, "optional", NA_character_,
         "VectorID", "char", NULL, "required", "vector_id",
         "ExperimentID", "char", NULL, "optional", NA_character_,
         "Tissue", "char", NULL, "required", "tissue",
         "TimePoint", "char", ~ stringr::str_pad(.x, 4, side = "left", pad = "0"),
         "required", "tp_days",
         "DNAFragmentation", "char", NULL, "optional", NA_character_,
         "PCRMethod", "char", NULL, "required", "pcr_method",
         "TagIDextended", "char", NULL, "optional", NA_character_,
         "Keywords", "char", NULL, "optional", NA_character_,
         "CellMarker", "char", NULL, "required", "cell_marker",
         "TagID", "char", NULL, "required", "tag_id",
         "NGSProvider", "char", NULL, "optional", NA_character_,
         "NGSTechnology", "char", NULL, "required", "ngs_tech",
         "ConverrtedFilesDir", "char", NULL, "optional", NA_character_,
         "ConverrtedFilesName", "char", NULL, "optional", NA_character_,
         "SourceFileFolder", "char", NULL, "optional", NA_character_,
         "SourceFileNameR1", "char", NULL, "optional", NA_character_,
         "SourceFileNameR2", "char", NULL, "optional", NA_character_,
         "DNAnumber", "char", NULL, "required", "dna_num",
         "ReplicateNumber", "int", NULL, "required", "pcr_replicate",
         "DNAextractionDate", "date", NULL, "optional", NA_character_,
         "DNAngUsed", "numeric", NULL, "required", NA_character_,
         "LinearPCRID", "char", NULL, "optional", NA_character_,
         "LinearPCRDate", "date", NULL, "optional", NA_character_,
         "SonicationDate", "date", NULL, "optional", NA_character_,
         "LigationDate", "date", NULL, "optional", NA_character_,
         "1stExpoPCRID", "char", NULL, "optional", NA_character_,
         "1stExpoPCRDate", "date", NULL, "optional", NA_character_,
         "2ndExpoID", "char", NULL, "optional", NA_character_,
         "2ndExpoDate", "date", NULL, "optional", NA_character_,
         "FusionPrimerPCRID", "char", NULL, "optional", NA_character_,
         "FusionPrimerPCRDate", "date", NULL, "optional", NA_character_,
         "PoolDate", "date", NULL, "optional", NA_character_,
         "SequencingDate", "date", NULL, "required", NA_character_,
         "VCN", "numeric", NULL, "required", "vcn",
         "Genome", "char", NULL, "required", "genome",
         "SequencingRound", "int", NULL, "optional", NA_character_,
         "Genotype", "char", NULL, "optional", NA_character_,
         "TestGroup", "char", NULL, "optional", NA_character_,
         "MOI", "char", NULL, "optional", NA_character_,
         "Engraftment", "numeric", NULL, "optional", NA_character_,
         "Transduction", "numeric", NULL, "optional", NA_character_,
         "Notes", "char", NULL, "optional", NA_character_,
         "AddedField1", "char", NULL, "optional", NA_character_,
         "AddedField2", "char", NULL, "optional", NA_character_,
         "AddedField3", "char", NULL, "optional", NA_character_,
         "AddedField4", "char", NULL, "optional", NA_character_,
         "concatenatePoolIDSeqRun", "char", NULL, "required",
         "vispa_concatenate",
         "AddedField6_RelativeBloodPercentage", "char", NULL, "optional",
         NA_character_,
         "AddedField7_PurityTestFeasibility", "char", NULL, "optional",
         NA_character_,
         "AddedField8_FacsSeparationPurity", "char", NULL, "optional",
         NA_character_,
         "Kapa", "numeric", NULL, "required", NA_character_,
         "ulForPool", "numeric", NULL, "required", NA_character_,
         "CompleteAmplificationID", "char", NULL, "required", "pcr_repl_id",
         "UniqueID", "char", NULL, "required", NA_character_,
         "StudyTestID", "char", NULL, "optional", NA_character_,
         "StudyTestGroup", "char", NULL, "optional", NA_character_,
         "MouseID", "char", NULL, "optional", NA_character_,
         "Tigroup", "char", NULL, "optional", NA_character_,
         "Tisource", "char", NULL, "optional", NA_character_,
         "PathToFolderProjectID", "char", NULL, "required", "proj_folder",
         "SamplesNameCheck", "char", NULL, "optional", NA_character_,
         "TimepointDays", "char", NULL, "optional", NA_character_,
         "TimepointMonths", "char", NULL, "optional", NA_character_,
         "TimepointYears", "char", NULL, "optional", NA_character_,
         "ng DNA corrected", "numeric", NULL, "optional", NA_character_
     )

 }
 
 # Internal: default columns and types of vispa2 stats cols
 .default_iss_stats_specs <- function() {

     tibble::tribble(
         ~names, ~types, ~transform, ~flag, ~tag,
         "RUN_NAME", "char", NULL, "required", NA_character_,
         "POOL", "char", NULL, "required", "vispa_concatenate",
         "TAG", "char", ~ stringr::str_replace_all(.x,
             pattern = "\\.",
             replacement = ""
         ), "required",
         "tag_seq",
         "RAW_READS", "int", NULL, "optional", NA_character_,
         "QUALITY_PASSED", "int", NULL, "optional", NA_character_,
         "PHIX_MAPPING", "int", NULL, "optional", NA_character_,
         "PLASMID_MAPPED_BYPOOL", "int", NULL, "optional", NA_character_,
         "BARCODE_MUX", "int", NULL, "required", NA_character_,
         "LTR_IDENTIFIED", "int", NULL, "optional", NA_character_,
         "TRIMMING_FINAL_LTRLC", "int", NULL, "optional", NA_character_,
         "LV_MAPPED", "int", NULL, "optional", NA_character_,
         "BWA_MAPPED_OVERALL", "int", NULL, "optional", NA_character_,
         "ISS_MAPPED_OVERALL", "int", NULL, "optional", NA_character_,
         "ISS_MAPPED_PP", "int", NULL, "optional", NA_character_
     )

 }
 
 # Mappings between input format and formats requested by external parsing
 # functions
 .types_mapping <- function() {

     tibble::tribble(
         ~types, ~mapping, ~fread,
         "char", "c", "character",
         "int", "i", "integer",
         "logi", "l", "logical",
         "numeric", "d", "numeric",
         "factor", "f", "factor",
         "date", "c", "charcter",
         "ymd", "c", "character",
         "ydm", "c", "character",
         "mdy", "c", "character",
         "myd", "c", "character",
         "dmy", "c", "character",
         "yq", "c", "character",
         "ym", "c", "character",
         "my", "c", "character",
         "ymd_hms", "c", "character",
         "ymd_hm", "c", "character",
         "ymd_h", "c", "character",
         "dmy_hms", "c", "character",
         "dmy_hm", "c", "character",
         "dmy_h", "c", "character",
         "mdy_hms", "c", "character",
         "mdy_hm", "c", "character",
         "mdy_h", "c", "character",
         "ydm_hms", "c", "character",
         "ydm_hm", "c", "character",
         "ydm_h", "c", "character"
     )

 }
 

 # Internal: associates column types with column names for a more precise
 # import

 .mandatory_IS_types <- function(mode) {

     specs <- mandatory_IS_vars(include_types = TRUE)
     specs_mappings <- specs %>%
         dplyr::left_join(.types_mapping(), by = "types")
     if (mode == "fread") {
         specs_mappings <- specs_mappings %>%
             dplyr::select(.data$names, .data$fread) %>%
             dplyr::group_by(.data$fread)
         types <- specs_mappings %>%
             dplyr::group_keys() %>%
             dplyr::pull(.data$fread)
         specs_mappings <- specs_mappings %>%
             dplyr::group_split(.keep = FALSE)
         names(specs_mappings) <- types
         types <- purrr::map(specs_mappings, ~ .x$names)
         return(types)
     }
     types <- as.list(setNames(specs_mappings$mapping, specs_mappings$names))

     return(types)

 }
 

 # Internal: associates column types with column names for a more precise
 # import
 .annotation_IS_types <- function(mode) {

     specs <- annotation_IS_vars(include_types = TRUE)
     specs_mappings <- specs %>%
         dplyr::left_join(.types_mapping(), by = "types")
     if (mode == "fread") {
         specs_mappings <- specs_mappings %>%
             dplyr::select(.data$names, .data$fread) %>%
             dplyr::group_by(.data$fread)
         types <- specs_mappings %>%
             dplyr::group_keys() %>%
             dplyr::pull(.data$fread)
         specs_mappings <- specs_mappings %>%
             dplyr::group_split(.keep = FALSE)
         names(specs_mappings) <- types
         types <- purrr::map(specs_mappings, ~ .x$names)
         return(types)
     }
     types <- as.list(setNames(specs_mappings$mapping, specs_mappings$names))

     return(types)

 }
 

 # Internal: associates column types with column names for a more precise
 # import

 .af_col_types <- function(mode) {

     specs <- association_file_columns(include_types = TRUE)
     specs_mappings <- specs %>%
         dplyr::left_join(.types_mapping(), by = "types")
     if (mode == "fread") {
         specs_mappings <- specs_mappings %>%
             dplyr::select(.data$names, .data$fread) %>%
             dplyr::group_by(.data$fread)
         types <- specs_mappings %>%
             dplyr::group_keys() %>%
             dplyr::pull(.data$fread)
         specs_mappings <- specs_mappings %>%
             dplyr::group_split(.keep = FALSE)
         names(specs_mappings) <- types
         types <- purrr::map(specs_mappings, ~ .x$names)
         return(types)
     }
     types <- as.list(setNames(specs_mappings$mapping, specs_mappings$names))

 }
 

 # Internal: used for file system alignment in import_association_file,
 # gives the names of the columns that respectively contain:
 # - the absolute path on disk of the project
 # - the path to the quantification folder
 # - the path to the iss folder
 .path_cols_names <- function() {
     list(project = "Path", quant = "Path_quant", iss = "Path_iss")
 }
 

 
 .default_matrix_suffixes <- function() {
 
 }
 

 .matrix_annotated_suffixes <- function() {
     c(".no0.annotated")
 }
 
 .matrix_not_annotated_suffixes <- function() {
     c("")
 }
 

 #' Names of the columns of the association file to consider for
 #' Vispa2 launch.
 #'
 #' Selection of column names from the association file to be considered for
 #' Vispa2 launch.
 #' NOTE: the `TagID` column appears only once but needs to be
 #' repeated twice for generating the launch file. Use the appropriate
 #' function to generate the file automatically.
 #'
 #' @return A character vector
 #' @export
 #'
 #' @examples
 #' reduced_AF_columns()
 reduced_AF_columns <- function() {

     required <- list(
         tag_id = "char",
         tissue = "char",
         subject = "char",
         tp_days = c("char", "numeric", "integer"),
         fusion_id = "char",
         pcr_repl_id = "char",
         cell_marker = "char",
         project_id = "char",
         vector_id = "char",
         pool_id = "char"
     )
     politics <- list(
         tag_id = "error",
         tissue = "error",
         subject = "error",
         tp_days = "first",
         fusion_id = "error",
         pcr_repl_id = "error",
         cell_marker = "error",
         project_id = "error",
         vector_id = "error",
         pool_id = "error"
     )
     tag_cols <- .check_required_cols(
         required_tags = required,
         vars_df = association_file_columns(TRUE),
         duplicate_politic = politics
     ) %>%
         dplyr::select(.data$names, .data$tag)
     data.table::setDT(tag_cols)
     return(tag_cols)

 }

 
 # Names of the columns of iss stats considered for aggregation
 # USED IN:
 # - .join_and_aggregate
 .agg_iss_cols <- function() {
     c(
         "BARCODE_MUX", "TRIMMING_FINAL_LTRLC",
         "LV_MAPPED",
         "BWA_MAPPED_OVERALL",
         "ISS_MAPPED_PP"
     )
 }
 
 .compressed_formats <- function() {
     c("gz", "bz2", "xz", "zip")
 }
 
 .supported_fread_compression_formats <- function() {
     c("gz", "bz2")
 }

 
 
 flag_logics <- function() {
     c("AND", "OR", "XOR", "NAND", "NOR", "XNOR")
 }

 
 ### Articles links
 .lentiviral_CIS_paper <- function() {
     paste0(
         "https://ashpublications.org/blood/article/117/20/5332/21206/",
         "Lentiviral-vector-common-integration-sites-in"
     )
 }
 
 .vispa2_paper_link <- function() {
     paste0("https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702242/")
 }
 
 .vispa2_paper_title <- function() {
     paste0(
         "VISPA2:A Scalable Pipeline for High-Throughput ",
         "Identification and Annotation of Vector Integration Sites"
     )
 }
 
 
 #' Required columns for refGene file.
 #'
 #' @return Character vector of column names
 #' @export
 #'
 #' @examples
 #' refGene_table_cols()
 refGene_table_cols <- function() {
     c(
         "name2", "chrom", "strand", "min_txStart", "max_txEnd",
         "minmax_TxLen", "average_TxLen", "name", "min_cdsStart",
         "max_cdsEnd", "minmax_CdsLen", "average_CdsLen"
     )
 }

 #' All available tags for dynamic vars look-up tables.

 #'

 #' @description
 #' Contains all information associated with critical tags used in the dynamic
 #' vars system. To know more see
 #' `vignette("setup_workflow", package="ISAnalytics")`.
 #'
 #' @return A data frame

 #' @export
 #'
 #' @examples

 #' available_tags()

 available_tags <- function() {

     data.table::data.table(
         tag = c(
             "chromosome", "locus", "is_strand", "gene_symbol", "gene_strand",
             "project_id", "pool_id", "fusion_id", "tag_seq", "subject",
             "vector_id",

             "tissue", "tp_days", "pcr_method", "cell_marker", "tag_id",
             "ngs_tech", "dna_num", "pcr_replicate", "vcn", "vispa_concatenate",
             "pcr_repl_id", "proj_folder", "genome",

             "vispa_concatenate", "tag_seq"
         ),
         needed_in = list(
             c(
                 "top_targeted_genes",
                 "CIS_grubbs",
                 "compute_near_integrations"
             ),
             c(
                 "top_targeted_genes",
                 "CIS_grubbs",
                 "compute_near_integrations"
             ),
             c(
                 "CIS_grubbs",
                 "compute_near_integrations"
             ),
             c(
                 "top_targeted_genes",
                 "CIS_grubbs",
                 "compute_near_integrations",
                 "CIS_volcano_plot"
             ),
             c(
                 "top_targeted_genes",
                 "CIS_grubbs"
             ),
             c(
                 "generate_default_folder_structure",
                 "import_Vispa2_stats", "remove_collisions",
                 "generate_Vispa2_launch_AF", "import_association_file",
                 "import_parallel_Vispa2Matrices"
             ),
             c(
                 "generate_Vispa2_launch_AF", "remove_collisions",
                 "import_association_file"
             ),
             c("generate_Vispa2_launch_AF"),
             c(
                 "generate_default_folder_structure",
                 "import_association_file", "import_Vispa2_stats"
             ),
             c(
                 "import_association_file",
                 "HSC_population_size_estimate"
             ),
             c("generate_Vispa2_launch_AF"),
             c(
                 "generate_Vispa2_launch_AF", "import_association_file",
                 "HSC_population_size_estimate"
             ),
             c("generate_Vispa2_launch_AF", "import_association_file"),
             c(),
             c(
                 "generate_Vispa2_launch_AF", "import_association_file",
                 "HSC_population_size_estimate"
             ),
             c("generate_Vispa2_launch_AF"),
             c(),
             c(),
             c("import_association_file", "remove_collisions"),
             c(),
             c(
                 "import_association_file", "generate_Vispa2_launch_AF",
                 "generate_default_folder_structure",
                 "import_Vispa2_stats", "import_parallel_Vispa2Matrices"
             ),
             c(
                 "pcr_id_column", "generate_Vispa2_launch_AF",
                 "import_association_file", "import_Vispa2_stats"
             ),
             c("import_association_file"),
             c(),
             c(
                 "import_association_file", "generate_Vispa2_launch_AF",
                 "generate_default_folder_structure",
                 "import_Vispa2_stats", "import_parallel_Vispa2Matrices"
             ),
             c(
                 "generate_default_folder_structure",
                 "import_association_file", "import_Vispa2_stats"
             )
         ),
         description = c(
             paste("Number of the chromosome"),
             paste("The locus at which the integration occurs"),
             paste("The DNA strand in which the integration occurs"),
             paste("The symbol of the gene"),
             paste("The strand of the gene"),
             paste("Unique identifier of a project"),
             paste("Unique identifier of a sequencing pool"),
             paste(
                 "Identification code/number of the",
                 "barcoded (SLiM-)PCR product included in the",
                 "sequencing library"
             ),
             paste("The barcode tag sequence"),
             paste(
                 "Unique identifier of a study subject",
                 "(usually a patient)"
             ),
             paste("Unique identifier of the vector used"),
             paste("The biological tissue the sample belongs to"),
             paste("The time point expressed in days"),
             paste("The PCR method used"),
             paste(
                 "Cell marker associated with isolated",
                 "cells carrying the IS"
             ),
             paste(
                 "Unique identifier of the barcode tag, as specified",
                 "in VISPA2 requirements"
             ),
             paste("Technology used for next generation sequencing"),
             paste(
                 "Identification code/number of the DNA extraction",
                 "from a specific biological sample"
             ),
             paste("Number of the PCR replicate"),
             paste("Vector copy number"),
             paste("Unique identifier of a pool as specified in VISPA2"),
             paste(
                 "Unique identifier of the pcr replicate, used as",
                 "key to join data and metadata"
             ),
             paste(
                 "Path on disk containing the standard VISPA2 folder",
                 "structure of the project"
             ),
             paste("The reference genome (e.g. 'hg19')"),
             paste("Unique identifier of a pool as specified in VISPA2"),
             paste("The barcode tag sequence")
         ),
         dyn_vars_tbl = c(
             "mand_vars", "mand_vars", "mand_vars",
             "annot_vars", "annot_vars",
             "af_vars", "af_vars", "af_vars", "af_vars", "af_vars",
             "af_vars", "af_vars", "af_vars", "af_vars", "af_vars",
             "af_vars", "af_vars", "af_vars", "af_vars", "af_vars",
             "af_vars", "af_vars", "af_vars", "af_vars",
             "iss_vars", "iss_vars"
         )
     )

 }