| 
						
						
							
								
							
						
						
					 | 
				
				 | 
				
					@ -5,6 +5,13 @@ library(reshape2) | 
				
			
			
		
	
		
			
				
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					library(Matrix) | 
				
			
			
		
	
		
			
				
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					library(CitFuns) | 
				
			
			
		
	
		
			
				
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				 | 
				
					library(BDCIT) | 
				
			
			
		
	
		
			
				
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				 | 
				
					library(openCyto) | 
				
			
			
		
	
		
			
				
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				 | 
				
					library(flowCore) | 
				
			
			
		
	
		
			
				
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				 | 
				
					library(flowWorkspace) | 
				
			
			
		
	
		
			
				
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				 | 
				
					library(CytoML) | 
				
			
			
		
	
		
			
				
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				 | 
				
					library(ggcyto) | 
				
			
			
		
	
		
			
				
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 | 
				
			
			
		
	
		
			
				
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					filter<-dplyr::filter | 
				
			
			
		
	
		
			
				
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 | 
				
			
			
		
	
		
			
				
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					print(getwd()) | 
				
			
			
		
	
		
			
				
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				 | 
				
					source("../sqlFunctions.R", encoding = "UTF-8") | 
				
			
			
		
	
	
		
			
				
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				 | 
				
					@ -19,6 +26,8 @@ rna<-data.frame("UMID"="","UM"="") | 
				
			
			
		
	
		
			
				
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					sqlInitialize(ruta="../ruta_database.R") | 
				
			
			
		
	
		
			
				
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				 | 
				
					# UI ---- | 
				
			
			
		
	
		
			
				
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 | 
				
			
			
		
	
		
			
				
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					ui <- fluidPage( | 
				
			
			
		
	
		
			
				
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 | 
				
			
			
		
	
		
			
				
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				 | 
				
					    # Application title | 
				
			
			
		
	
	
		
			
				
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					@ -27,6 +36,8 @@ ui <- fluidPage( | 
				
			
			
		
	
		
			
				
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					    #sidebarLayout( | 
				
			
			
		
	
		
			
				
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				 | 
				
					    #Navbar | 
				
			
			
		
	
		
			
				
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					    navbarPage("BDAccess", | 
				
			
			
		
	
		
			
				
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				 | 
				
					
 | 
				
			
			
		
	
		
			
				
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				 | 
				
					## Update ---- | 
				
			
			
		
	
		
			
				
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					        tabPanel("Update", | 
				
			
			
		
	
		
			
				
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					            sidebarPanel( | 
				
			
			
		
	
		
			
				
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					                selectInput("dbtype", "", selected="UM", choices=c("UM", "OV","CC")), | 
				
			
			
		
	
	
		
			
				
					| 
						
						
						
							
								
							
						
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				 | 
				
					@ -52,6 +63,8 @@ ui <- fluidPage( | 
				
			
			
		
	
		
			
				
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					                ) | 
				
			
			
		
	
		
			
				
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					            ) | 
				
			
			
		
	
		
			
				
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					        ), | 
				
			
			
		
	
		
			
				
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				 | 
				
					## Visor ---- | 
				
			
			
		
	
		
			
				
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					        tabPanel("Visor", | 
				
			
			
		
	
		
			
				
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				 | 
				
					            sidebarPanel( | 
				
			
			
		
	
		
			
				
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				 | 
				
					                radioButtons("nhc", label = h3("Código"), | 
				
			
			
		
	
	
		
			
				
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				 | 
				
					@ -63,9 +76,35 @@ ui <- fluidPage( | 
				
			
			
		
	
		
			
				
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					            mainPanel( | 
				
			
			
		
	
		
			
				
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					                htmlOutput("report"), | 
				
			
			
		
	
		
			
				
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					                h3("Nitrogen"), | 
				
			
			
		
	
		
			
				
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					                tableOutput("nitrogen") | 
				
			
			
		
	
		
			
				
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					                tableOutput("nitrogen"), | 
				
			
			
		
	
		
			
				
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				 | 
				
					                plotOutput("visorplot", height = "1000px") | 
				
			
			
		
	
		
			
				
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					            ) | 
				
			
			
		
	
		
			
				
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					        ), | 
				
			
			
		
	
		
			
				
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				 | 
				
					## Citometría ---- | 
				
			
			
		
	
		
			
				
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					        tabPanel("Citometría", | 
				
			
			
		
	
		
			
				
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				 | 
				
					                 sidebarPanel( | 
				
			
			
		
	
		
			
				
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					                     selectInput("phenotype", "Tipo de análisis", selected="Pop", choices=c("Pop", "IC")), | 
				
			
			
		
	
		
			
				
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					                 ), | 
				
			
			
		
	
		
			
				
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					                 mainPanel( | 
				
			
			
		
	
		
			
				
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					                     tabsetPanel( | 
				
			
			
		
	
		
			
				
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					                         tabPanel("Entrada", | 
				
			
			
		
	
		
			
				
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					                             actionButton("goButtonDir","Selecciona directorio fenotipo"), | 
				
			
			
		
	
		
			
				
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					                             textOutput("session"), | 
				
			
			
		
	
		
			
				
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					                             hr(), | 
				
			
			
		
	
		
			
				
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				 | 
				
					                             actionButton("fcsconvert", "Convertir a fcs"), | 
				
			
			
		
	
		
			
				
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				 | 
				
					                             hr(), | 
				
			
			
		
	
		
			
				
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				 | 
				
					                             actionButton("pngexport", "Exportar informes"), | 
				
			
			
		
	
		
			
				
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				 | 
				
					                             actionButton("popexport", "Actualizar BBDD") | 
				
			
			
		
	
		
			
				
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					                        ), | 
				
			
			
		
	
		
			
				
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					                        tabPanel("Visor", | 
				
			
			
		
	
		
			
				
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 | 
				
			
			
		
	
		
			
				
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					                        ) | 
				
			
			
		
	
		
			
				
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					                     ) | 
				
			
			
		
	
		
			
				
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					                 ) | 
				
			
			
		
	
		
			
				
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					        ), | 
				
			
			
		
	
		
			
				
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				 | 
				
					
 | 
				
			
			
		
	
		
			
				
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				 | 
				
					## scRNAseq ---- | 
				
			
			
		
	
		
			
				
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					        tabPanel("scRNAseq", | 
				
			
			
		
	
		
			
				
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				 | 
				
					                 sidebarPanel( | 
				
			
			
		
	
		
			
				
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				 | 
				
					                     textInput("sqlquery", label = "sqlquery", value = ""), | 
				
			
			
		
	
	
		
			
				
					| 
						
						
						
							
								
							
						
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				 | 
				
					@ -87,10 +126,11 @@ ui <- fluidPage( | 
				
			
			
		
	
		
			
				
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					) | 
				
			
			
		
	
		
			
				
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					# Define server logic required to draw a histogram | 
				
			
			
		
	
		
			
				
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					# Server ---- | 
				
			
			
		
	
		
			
				
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				 | 
				
					server <- function(input, output) { | 
				
			
			
		
	
		
			
				
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					     | 
				
			
			
		
	
		
			
				
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					 | 
				
				 | 
				
					    ## Update | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					     | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					
 | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					## Update ---- | 
				
			
			
		
	
		
			
				
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				 | 
				
					
 | 
				
			
			
		
	
		
			
				
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					 | 
				
				 | 
				
					    values <- reactiveValues() | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    values[["DF"]]<-DF | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    values[["samples"]]<-samples | 
				
			
			
		
	
	
		
			
				
					| 
						
							
								
							
						
						
							
								
							
						
						
					 | 
				
				 | 
				
					@ -618,8 +658,9 @@ server <- function(input, output) { | 
				
			
			
		
	
		
			
				
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					        } | 
				
			
			
		
	
		
			
				
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					    }) | 
				
			
			
		
	
		
			
				
					 | 
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				 | 
				
					     | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    ## Visor | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					     | 
				
			
			
		
	
		
			
				
					 | 
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				 | 
				
					
 | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					## Visor ---- | 
				
			
			
		
	
		
			
				
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					 | 
				
				 | 
				
					
 | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    output$report<-renderUI({ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        samples<-sqlFetch(dta, "samples") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        if (input$nhc == 1){samples_sel<-samples %>% filter(OVID == input$id)} | 
				
			
			
		
	
	
		
			
				
					| 
						
							
								
							
						
						
							
								
							
						
						
					 | 
				
				 | 
				
					@ -786,8 +827,206 @@ server <- function(input, output) { | 
				
			
			
		
	
		
			
				
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 | 
				
			
			
		
	
		
			
				
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					    }) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					     | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    ## scRNAseq | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    output$visorplot<-renderPlot({ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        if (input$nhc == 3){ | 
				
			
			
		
	
		
			
				
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					 | 
				
				 | 
				
					            pops<-sqlFetch(dta, "POPULATIONS") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            g_pop<-pops %>% dplyr::filter(samples == input$id) %>% gather(pop,value,-samples) %>% | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                mutate(pop=factor(pop, levels=c("CD45pos_Alive","T_cells","CD8","CD4","DN","NK", "B_cells", | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                                                "CD45neg_LDneg","EpCAMneg_HLAIneg","EpCAMneg_HLAIpos","EpCAMpos_HLAIpos"))) %>%  | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                ggplot(aes(pop, value))+ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                    geom_bar(stat="identity", color="black", fill="grey70")+ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                    labs(title = input$id, y="% parent", x="")+ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                    theme_bw()+ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                    theme(axis.text.x = element_text(angle=90, hjust=1, vjust=0.5)) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            tl<-sqlFetch(dta, "IC") %>% filter(samples == input$id) | 
				
			
			
		
	
		
			
				
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					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            mtl<-melt(tl, variable.name = "Receptors") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            mtl$Receptors<-as.character(mtl$Receptors) #Para poder depurar bien el texto, lo pasamos a tipo character | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            mtl$Receptors<-gsub("n","-",mtl$Receptors, fixed = T) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            mtl$Receptors<-gsub("p","+",mtl$Receptors, fixed = T) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            mtl$Receptors<-gsub("_"," ",mtl$Receptors) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            mtl[mtl$value < 1, "Receptors"]<-"Other" | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            mtl$Receptors<-gsub("[A-Z]*-*[0-9T]- *", "", mtl$Receptors) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            mtl$Receptors<-gsub("+ $", "", mtl$Receptors) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            mtl$Receptors[mtl$Receptors == ""]<-"All Negative" | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            mtl$Receptors<-factor(mtl$Receptors) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            mtl$Population<-factor(mtl$Population, levels = c("CD8", "CD4")) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            # colorCount<-length(unique(mtl$Receptors)) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            # getPalette = colorRampPalette(RColorBrewer::brewer.pal(12, "Set3")) | 
				
			
			
		
	
		
			
				
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					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            color<-c(c("CTLA4+ LAG3+ PD1+ TIGIT+ TIM3+"="black","All Negative"="white","Other"="grey50", "PD1+"="#C07AFF", "CTLA4+"="#3EB3DE","TIM3+"="#5EF551","LAG3+"="#DEBB3E","TIGIT+"="#FA7055"), | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                     c("CTLA4+ PD1+"="#6666FF","PD1+ TIM3+"="#849CA8", "LAG3+ PD1+"="#C47F9F","PD1+ TIGIT+"="#D259AA", "CTLA4+ TIM3+"="#4ED498", "CTLA4+ LAG3+"="#8EB78E", "CTLA4+ TIGIT+"="#9C929A", "LAG3+ TIM3+"="#9ED848", "TIGIT+ TIM3+"="#ACB353", "LAG3+ TIGIT+"="#EC964A"), | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                     c("CTLA4+ PD1+ TIGIT+"="#B86B6A","CTLA4+ PD1+ TIGIT+ TIM3+"="#B81515","LAG3+ PD1+ TIGIT+"="#007D8A", "PD1+ TIGIT+ TIM3+"="#D64545", "LAG3+ PD1+ TIGIT+ TIM3+"="#0f5860", "LAG3+ TIGIT+ TIM3+"="#50cad3")) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            g_IC<-ggplot(mtl, aes(samples, value, fill=Receptors))+ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                geom_bar(stat="summary", fun="sum",color="black")+ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                labs(x="Patient", y="% CD8+", fill="")+ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                facet_grid(.~Population)+ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                scale_fill_manual(values = color[levels(mtl$Receptors)[levels(mtl$Receptors) %in% unique(mtl$Receptors)]])+ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                theme_bw()+ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                theme(axis.text.x=element_text(angle=45, hjust=1)) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            ggpubr::ggarrange(g_pop, g_IC, heights = c(0.4, 0.6), ncol = 1) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        } | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    }) | 
				
			
			
		
	
		
			
				
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					     | 
				
			
			
		
	
		
			
				
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 | 
				
			
			
		
	
		
			
				
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				 | 
				
					## Citometría ---- | 
				
			
			
		
	
		
			
				
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				 | 
				
					
 | 
				
			
			
		
	
		
			
				
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				 | 
				
					    observe({ | 
				
			
			
		
	
		
			
				
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					 | 
				
				 | 
				
					        if(input$goButtonDir > 0){ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            cito_dir<<-choose.dir() %>% gsub("\\","/",. ,fixed=T) %>% paste0("/") | 
				
			
			
		
	
		
			
				
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					 | 
				
				 | 
				
					
 | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            output$session <- renderText( | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                    cito_dir | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                ) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        } | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    }) | 
				
			
			
		
	
		
			
				
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 | 
				
			
			
		
	
		
			
				
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				 | 
				
					    observeEvent(input$fcsconvert,{ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        route<-cito_dir | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					         | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        files<-list.files(route, ".LMD") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        for (lmd in files){ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            fcs<-read.FCS(paste0(route,lmd), dataset = 2) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            # fcs@parameters$desc<-c("FS-A","SS-A", paste("FL",1:10,"-A", sep = ""), "TIME") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            # fcs@parameters$desc<-c("FS-H","FS-A","FS-W","SS-H","SS-A","TIME", paste("FL",1:10,"-A", sep = "")) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            keyword(fcs)['$FIL']<-paste0(gsub(".LMD","",lmd), ".fcs") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            write.FCS(fcs, paste0(route, gsub(".LMD","",lmd), ".fcs")) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        } | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    }) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					     | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    observeEvent(input$pngexport,{ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        if (input$phenotype == "Pop"){ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            route<-cito_dir | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            ws<-open_flowjo_xml(paste0(route,"Populations.wsp")) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            gs<-flowjo_to_gatingset(ws, name="All Samples") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            sampleNames(gs)<-sapply(sampleNames(gs), function(x) strsplit(x, "Pop ")[[1]][2]) %>%  | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                gsub("[[:space:]][0-9]*.fcs_.[0-9]*","", . , perl = T) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            for (samp in sampleNames(gs)){ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                print(samp) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                p<-autoplot(gs[[samp]], bins=64) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                ggsave(paste0(route, samp,".pop.png"),p,width = 10, height = 10) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            } | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        } | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					         | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        if (input$phenotype == "IC"){ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            route<-cito_dir | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            ws<-open_flowjo_xml(paste0(route,"IC.wsp")) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            gs<-flowjo_to_gatingset(ws, name="All Samples") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            sampleNames(gs)<-sapply(sampleNames(gs), function(x) strsplit(x, "ICs ")[[1]][2]) %>%  | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                gsub("[[:space:]][0-9]*.fcs_.[0-9]*","", . , perl = T) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            names<-sampleNames(gs) %>% gsub("ab|Ab|AB|iso|Iso|ISO| ","",.) %>% unique() | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            nodes<-gs_get_pop_paths(gs) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            nodes_parent<-nodes[!grepl("CTLA4|LAG3|PD1|TIGIT|TIM3|root$", nodes)] | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            nodes_cd4<-nodes[grepl("CTLA4$|LAG3$|PD1$|TIGIT$|TIM3$", nodes) & grepl("/CD4/",nodes)] | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            nodes_cd8<-nodes[grepl("CTLA4$|LAG3$|PD1$|TIGIT$|TIM3$", nodes) & grepl("/CD8/",nodes)] | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            for (id in names){ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                print(id) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                iso<-sampleNames(gs)[grepl(id, sampleNames(gs)) & grepl("iso",sampleNames(gs))] | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                ab<-sampleNames(gs)[grepl(id, sampleNames(gs)) & grepl("ab",sampleNames(gs))] | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                 | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                g1<-ggcyto_arrange(autoplot(gs[[ab]], nodes_parent, bins=128), nrow=1) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                g2<-ggcyto_arrange(autoplot(gs[[iso]], nodes_cd8, bins=64), nrow=1) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                g3<-ggcyto_arrange(autoplot(gs[[ab]], nodes_cd8, bins=64), nrow=1) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                g4<-ggcyto_arrange(autoplot(gs[[iso]], nodes_cd4, bins=64), nrow=1) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                g5<-ggcyto_arrange(autoplot(gs[[ab]], nodes_cd4, bins=64), nrow=1) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                g_all<-gridExtra::gtable_rbind(g1,g2,g3,g4,g5) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                ggsave(paste0(route,id,".IC.png"), g_all, width = 10, height = 10) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            } | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        } | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    }) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					         | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    observeEvent(input$popexport,{ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        if (input$phenotype == "Pop"){ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            route<-cito_dir | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            ws<-open_flowjo_xml(paste0(route,"Populations.wsp")) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            gs<-flowjo_to_gatingset(ws, name="All Samples") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            sampleNames(gs)<-sapply(sampleNames(gs), function(x) strsplit(x, "Pop ")[[1]][2]) %>%  | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                gsub("[[:space:]][0-9]*.fcs_.[0-9]*","", . , perl = T) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            nodes<-sapply(strsplit(gs_get_pop_paths(gs), "/"), tail, 1) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            nodes<-nodes[grepl("_",nodes)] | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop<-gs_pop_get_stats(gs, nodes=nodes,type="percent") %>% as.data.frame %>% mutate(percent=percent*100) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop[,"pop"]<-gsub("_","",pop$pop) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop$pop<-gsub(" ","_",pop$pop) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop$pop<-gsub("+","pos",pop$pop, fixed=T) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop$pop<-gsub("-","neg",pop$pop, fixed=T) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop<-rename(pop, "samples"="sample") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop$percent<-round(pop$percent, digits=2) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop_sp<-pop %>% spread(pop, percent) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop_sql<-sqlFetch(dta, "POPULATIONS") %>% slice(0) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop_sp<-pop_sp %>% merge(pop_sql, all=T) %>% select(colnames(pop_sql)) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            vartypes<-rep("Number", pop_sp %>% select(-samples) %>% colnames %>% length) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            names(vartypes)<-pop_sp %>% select(-samples) %>% colnames | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            sqlSave(dta, pop_sp, tablename="POPULATIONS", append = T, varTypes = vartypes, rownames = F) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            print("Tabla POPULATIONS sincronizada.") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        } | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        if (input$phenotype == "IC"){ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            route<-cito_dir | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            ws<-open_flowjo_xml(paste0(route,"IC.wsp")) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            gs<-flowjo_to_gatingset(ws, name="All Samples") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            sampleNames(gs)<-sapply(sampleNames(gs), function(x) strsplit(x, "ICs ")[[1]][2]) %>%  | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                gsub("[[:space:]][0-9]*.fcs_.[0-9]*","", . , perl = T) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            nodes<-gs_get_pop_paths(gs) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            # nodes<-gsub("â\u0081»", "-", nodes) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            # nodes<-gsub("â\u0081º", "+", nodes) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            nodes<-nodes[grepl("CTLA4", nodes)] | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            nodes<-nodes[!grepl("CD4$|CD8$|CTLA4$|TIM3$|PD1$|LAG3$|TIGIT$|/CTLA4â\u0081»$|/TIM3â\u0081»$|/PD1â\u0081»$|/LAG3â\u0081»$|/TIGITâ\u0081»$", nodes)] | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop<-gs_pop_get_stats(gs, nodes=nodes,type="percent") %>% as.data.frame %>% mutate(percent=percent*100) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop$percent<-round(pop$percent, digits=2) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop$pop<-gsub("â\u0081»", "n", pop$pop) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop$pop<-gsub("â\u0081º", "p", pop$pop) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop$pop<-gsub(" ", "_", pop$pop) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop["Type"]<-"ab" | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop[grepl("iso|ISO|Iso",pop$sample),"Type"]<-"iso" | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop$sample<-gsub("iso|ISO|Iso|ab|AB|Ab| ","",pop$sample) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop_sp<-pop %>% spread(Type, percent) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop_sp["Net"]<-pop_sp$ab | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop_sp[!grepl("CTLA4n_LAG3n_PD1n_TIGITn_TIM3n",pop_sp$pop),"Net"]<-pop_sp[!grepl("CTLA4n_LAG3n_PD1n_TIGITn_TIM3n",pop_sp$pop),"ab"]-pop_sp[!grepl("CTLA4n_LAG3n_PD1n_TIGITn_TIM3n",pop_sp$pop),"iso"] | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop_sp$Net[pop_sp$Net < 0]<-0 | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop_sp["Population"]<-str_extract(pop_sp$pop, "/CD[4,8]{1}/") %>% gsub("/","",.) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop_sp$pop<-sapply(strsplit(pop_sp$pop, "/"), tail, 1) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop_sp<-pop_sp %>% select(-ab,-iso) %>% spread(pop,Net) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop_sp$`CTLA4n_LAG3n_PD1n_TIGITn_TIM3n`<- pop_sp %>% select(-`CTLA4n_LAG3n_PD1n_TIGITn_TIM3n`) %>% group_by(sample,Population) %>%  | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					                gather(pop, value, -sample,-Population) %>% summarise(n=100-sum(value)) %>% pull(n) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            pop_sp <- rename(pop_sp, "samples"="sample") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            vartypes<-rep("Number", pop_sp %>% select(-samples, -Population) %>% colnames %>% length) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            names(vartypes)<-pop_sp %>% select(-samples, -Population) %>% colnames | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					             | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            sqlSave(dta, pop_sp, tablename="IC", append = T, varTypes = vartypes, rownames = F) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					            print("Tabla IC sincronizada.") | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        } | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    })  | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					
 | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					
 | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					## scRNAseq ---- | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					
 | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					    output$PATID = renderUI({ | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        observeEvent(input$goButton, {}) | 
				
			
			
		
	
		
			
				
					 | 
					 | 
				
				 | 
				
					        sc_cod<-sqlFetch(dta, "CNAG") %>% pull(CODIGO) | 
				
			
			
		
	
	
		
			
				
					| 
						
							
								
							
						
						
						
					 | 
				
				 | 
				
					
 |