# GNU General Public License v3.0 (https://github.com/IanevskiAleksandr/sc-type/blob/master/LICENSE)
# Written by Aleksandr Ianevski <aleksandr.ianevski@helsinki.fi>, June 2021
#
# Functions on this page:
# gene_sets_prepare: prepare gene sets and calculate marker sensitivity from input Cell Type excel file
#
# @params: path_to_db_file - DB file with cell types
# @cell_type - cell type (e.g. Immune system, Liver, Pancreas, Kidney, Eye, Brain)
#

gene_sets_prepare <- function(path_to_db_file, cell_type){
  
  cell_markers = openxlsx::read.xlsx(path_to_db_file)
  cell_markers = cell_markers[cell_markers$tissueType == cell_type,] 
  cell_markers$geneSymbolmore1 = gsub(" ","",cell_markers$geneSymbolmore1); cell_markers$geneSymbolmore2 = gsub(" ","",cell_markers$geneSymbolmore2)
  
  # correct gene symbols from the given DB (up-genes)
  cell_markers$geneSymbolmore1 = sapply(1:nrow(cell_markers), function(i){
    
    markers_all = gsub(" ", "", unlist(strsplit(cell_markers$geneSymbolmore1[i],",")))
    markers_all = toupper(markers_all[markers_all != "NA" & markers_all != ""])
    markers_all = sort(markers_all)
    
    if(length(markers_all) > 0){
      suppressMessages({markers_all = unique(na.omit(checkGeneSymbols(markers_all)$Suggested.Symbol))})
      paste0(markers_all, collapse=",")
    } else {
      ""
    }
  })
  
  # correct gene symbols from the given DB (down-genes)
  cell_markers$geneSymbolmore2 = sapply(1:nrow(cell_markers), function(i){
    
    markers_all = gsub(" ", "", unlist(strsplit(cell_markers$geneSymbolmore2[i],",")))
    markers_all = toupper(markers_all[markers_all != "NA" & markers_all != ""])
    markers_all = sort(markers_all)
    
    if(length(markers_all) > 0){
      suppressMessages({markers_all = unique(na.omit(checkGeneSymbols(markers_all)$Suggested.Symbol))})
      paste0(markers_all, collapse=",")
    } else {
      ""
    }
  })
  
  cell_markers$geneSymbolmore1 = gsub("///",",",cell_markers$geneSymbolmore1);cell_markers$geneSymbolmore1 = gsub(" ","",cell_markers$geneSymbolmore1)
  cell_markers$geneSymbolmore2 = gsub("///",",",cell_markers$geneSymbolmore2);cell_markers$geneSymbolmore2 = gsub(" ","",cell_markers$geneSymbolmore2)
   
  gs = lapply(1:nrow(cell_markers), function(j) gsub(" ","",unlist(strsplit(toString(cell_markers$geneSymbolmore1[j]),",")))); names(gs) = cell_markers$cellName
  gs2 = lapply(1:nrow(cell_markers), function(j) gsub(" ","",unlist(strsplit(toString(cell_markers$geneSymbolmore2[j]),",")))); names(gs2) = cell_markers$cellName
  
  list(gs_positive = gs, gs_negative = gs2)
}