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server.R
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library(viridis)
library(RSQLite)
library(manipulateWidget)
library(highcharter)
library(tm)
library(reshape2)
library(plyr)
library(htmltools)
library(RColorBrewer)
library(shiny)
library(shinyBS)
source(file = 'functions_helpers.R')
shinyInput <- function(FUN, len, id, ...)
{
inputs <- character(len)
for (i in seq_len(len))
{
inputs[i] <- as.character(FUN(paste0(id, i), style='padding:4px;font-size:80%', ...))
}
inputs
}
shinyServer(
function(input, output, session)
{
# DATA IMPORT -------------------------------------------------------------
#Database for the pvalue = f(age) for each gene, tissue and variable
# DBconnection3 <- dbConnect(RSQLite::SQLite(),
# dbname = "DB_pvalue_ShARP-LM.db")
#Significance pvalue = f(age) for a single gene across tissue
#Need to take gene-specific information from DB_pvalue_ShARP-LM.db
#p_Alterations gathers signficiance for all tissue for a single genes and variable
p_Alterations <- reactive({
gene <- input$gene
variable <- input$variable_Gene_Alteration
validate(need(!is.null(gene) & gene != "", ""))
tissue <- geneList$tissue[[match(gene, geneList$gene)]]
modifiedTissuename <- gsub("-", "_", tissue)
modifiedTissuename <- gsub(" ", "", modifiedTissuename)
modifiedTissuename <- gsub("\\(", "", modifiedTissuename)
modifiedTissuename <- gsub("\\)", "", modifiedTissuename)
p <- data.frame()
for (i in 1:length(modifiedTissuename))
{
if (tissue[i] %in% c("Ovary", "Uterus", "Vagina", "Prostate", "Fallopian Tube", "Testis") & variable %in% c("Gender", "Int_Age_Gender"))
{
tmp <- NULL
} else
{
# #SQL database
# tmp <- dbGetQuery(DBconnection3, paste("SELECT * FROM", paste0(modifiedTissuename[i], "_", variable)))
# #RDS files local
# tmp <- readRDS(paste("/genedata/home/arthur/Documents/GTEx/shiftingLM_genes/shiny_app/RDS files/DB_pvalue_ShARP-LM/",
# modifiedTissuename[i], "_", variable, ".RDS", sep = ""))
#RDS files online
tmp <- readRDS(paste("data/DB_pvalue_ShARP-LM/",
modifiedTissuename[i], "_",
variable, ".RDS", sep = ""))
#gene <- gsub("-", "_", gene) # '-' creates issues when calling database so '-' were replaced by "_" in the database's names
#gene <- gsub("\\.", "_", gene) # '.' creates issues when calling database so '-' were replaced by "_" in the database's names
tmp <- tmp[tmp$gene == gene,]
tmp <- tmp[, -1]
tmp <- -log10(tmp)
fit <- smooth.spline(as.numeric(colnames(tmp)), tmp)
fit <- predict(fit, seq(26, 64, by = 0.5))$y
tmp <- data.frame(t(fit))
colnames(tmp) <- seq(26, 64, by = 0.5)
rownames(tmp) <- tissue[i]
}
p <- rbind(p, tmp)
}
p
})
#alterations significance for a single gene, tissue and variable
p_Alteration_gene <- reactive({
gene <- input$gene
variable <- input$variable_Gene_Alteration
tissue <- input$tissue
validate(need(!is.null(tissue) & tissue != "" & tissue != "All tissues", ""))
modifiedTissuename <- gsub("-", "_", tissue)
modifiedTissuename <- gsub(" ", "", modifiedTissuename)
modifiedTissuename <- gsub("\\(", "", modifiedTissuename)
modifiedTissuename <- gsub("\\)", "", modifiedTissuename)
if (tissue %in% c("Ovary", "Uterus", "Vagina", "Prostate", "Fallopian Tube", "Testis") & variable %in% c("Gender", "Int_Age_Gender"))
{
pvalueData <- NULL
} else
{
# #SQL database
# pvalueData <- dbGetQuery(DBconnection3, paste("SELECT * FROM", paste0(modifiedTissuename, "_", variable)))
# #RDS files local
# pvalueData <- readRDS(paste("/genedata/home/arthur/Documents/GTEx/shiftingLM_genes/shiny_app/RDS files/DB_pvalue_ShARP-LM/",
# modifiedTissuename, "_", variable, ".RDS", sep = ""))
#RDS files online
pvalueData <- readRDS(paste("data/DB_pvalue_ShARP-LM/",
modifiedTissuename, "_", variable, ".RDS",
sep = ""))
pvalueData <- pvalueData[pvalueData$gene == gene,]
pvalueData <- pvalueData[, -1]
}
pvalueData
})
# coefs linear model per gene, fit ShARP-LM per gene in entire age range, per condition
fit_abline <- reactive({
gene <- input$gene
variable <- input$variable_Gene_Alteration
tissue <- input$tissue
validate(need(!is.null(tissue) & tissue != "" & tissue != "All tissues", ""))
modifiedTissuename <- gsub("-", "_", tissue)
modifiedTissuename <- gsub(" ", "", modifiedTissuename)
modifiedTissuename <- gsub("\\(", "", modifiedTissuename)
modifiedTissuename <- gsub("\\)", "", modifiedTissuename)
if (tissue %in% c("Ovary", "Uterus", "Vagina", "Prostate", "Fallopian Tube", "Testis") & variable %in% c("Gender", "Int_Age_Gender"))
{
result <- NULL
} else
{
#RDS files online
result <- readRDS(paste("data/DB_pvalue_ShARP-LM_EntireAgeRange_abline/",
modifiedTissuename, "_", variable, ".RDS",
sep = ""))
#result <- result[result$gene == gene,]
result <- result[, -c(4)]
}
result
})
# _2 because it is for the tissue tab, alteration has a different id
fit_abline_2 <- reactive({
gene <- selectedGene()
variable <- input$variable_model_2
tissue <- input$tissue_2
validate(need(!is.null(tissue) & tissue != "" & tissue != "All tissues", ""))
modifiedTissuename <- gsub("-", "_", tissue)
modifiedTissuename <- gsub(" ", "", modifiedTissuename)
modifiedTissuename <- gsub("\\(", "", modifiedTissuename)
modifiedTissuename <- gsub("\\)", "", modifiedTissuename)
if (tissue %in% c("Ovary", "Uterus", "Vagina", "Prostate", "Fallopian Tube", "Testis") & variable %in% c("Gender", "Int_Age_Gender"))
{
result <- NULL
} else
{
#RDS files online
result <- readRDS(paste("data/DB_pvalue_ShARP-LM_EntireAgeRange_abline/",
modifiedTissuename, "_", variable, ".RDS",
sep = ""))
#result <- result[result$gene == gene,]
result <- result[, -c(4)]
}
result
})
#significance and t value for a single gene, tissue and variable
Sig_Mag_Gene_perTissueVariable <- reactive({
gene <- input$gene
variable <- input$variable_Gene_Alteration
tissue <- input$tissue
validate(need(!is.null(tissue) & tissue != "" & tissue != "All tissues", ""))
modifiedTissuename <- gsub("-", "_", tissue)
modifiedTissuename <- gsub(" ", "", modifiedTissuename)
modifiedTissuename <- gsub("\\(", "", modifiedTissuename)
modifiedTissuename <- gsub("\\)", "", modifiedTissuename)
if (tissue %in% c("Ovary", "Uterus", "Vagina", "Prostate", "Fallopian Tube", "Testis") & variable %in% c("Gender", "Int_Age_Gender"))
{
result <- NULL
} else
{
#RDS files online
result <- readRDS(paste("data/DB_pvalue_ShARP-LM_EntireAgeRange/",
modifiedTissuename, "_", variable, ".RDS",
sep = ""))
#result <- result[result$gene == gene,]
result <- result[, -c(4)]
}
result
})
#significance and t value for a single gene, tissue and variable
# _2 because it is for the tissue tab, alteration has a different id
Sig_Mag_Gene_perTissueVariable_2 <- reactive({
gene <- selectedGene()
variable <- input$variable_model_2
tissue <- input$tissue_2
validate(need(!is.null(tissue) & tissue != "" & tissue != "All tissues", ""))
modifiedTissuename <- gsub("-", "_", tissue)
modifiedTissuename <- gsub(" ", "", modifiedTissuename)
modifiedTissuename <- gsub("\\(", "", modifiedTissuename)
modifiedTissuename <- gsub("\\)", "", modifiedTissuename)
if (tissue %in% c("Ovary", "Uterus", "Vagina", "Prostate", "Fallopian Tube", "Testis") & variable %in% c("Gender", "Int_Age_Gender"))
{
result <- NULL
} else
{
#RDS files online
result <- readRDS(paste("data/DB_pvalue_ShARP-LM_EntireAgeRange/",
modifiedTissuename, "_", variable, ".RDS",
sep = ""))
#result <- result[result$gene == gene,]
result <- result[, -c(4)]
}
result
})
#p gather significance for all genes given a tissue and a variable
p <- reactive({
validate(need(input$tissue_2 != "All tissues" & input$tissue_2 != "", ""))
if (input$tissue_2 %in% c("Ovary", "Uterus", "Vagina", "Prostate", "Fallopian Tube", "Testis") & input$variable_model_2 %in% c("Gender", "Int_Age_Gender"))
{
p <- NULL
} else
{
modifiedTissuename <- gsub("-", "_", input$tissue_2)
modifiedTissuename <- gsub(" ", "", modifiedTissuename)
modifiedTissuename <- gsub("\\(", "", modifiedTissuename)
modifiedTissuename <- gsub("\\)", "", modifiedTissuename)
# #SQL database
# p <- dbGetQuery(DBconnection3, paste("SELECT * FROM", paste0(modifiedTissuename, "_", input$variable_model_2)))
# #RDS files local
# p <- readRDS(paste("/genedata/home/arthur/Documents/GTEx/shiftingLM_genes/shiny_app/RDS files/DB_pvalue_ShARP-LM/",
# modifiedTissuename, "_", input$variable_model_2, ".RDS", sep = ""))
#RDS files online
p <- readRDS(paste("data/DB_pvalue_ShARP-LM/",
modifiedTissuename, "_", input$variable_model_2,
".RDS", sep = ""))
rownames(p) <- p$gene
p <- p[,-1]
}
p
})
peak <- readRDS("data/peaks_plot_2.RDS") #to know the FDR for each peak for FDRvsAge
AgeWavesList <- readRDS("data/FDR_Interpolation_Tissue.RDS")
geneList <- readRDS("data/DT_NbTissuePerGene.RDS")
donorCondition <- readRDS("data/donorCondition.RDS")
conditionID <- readRDS("data/conditionID.RDS")
technicalCondition <- readRDS("data/technicalCondition.RDS")
Cluster_Reactome <- readRDS("data/Cluster_Reactome.RDS")
Cluster_Reactome_affiliation <- readRDS("data/Reactome_cluster_Affiliation.RDS")
moduleInfo <- readRDS("data/moduleInfo_Corrected_Atlas_v4.RDS")
# color2 <- c("#8DD3C7", "#FFFFB3", "#FB8072", "#80B1D3", "#FDB462", "#B3DE69", "#FCCDE5", "#D9D9D9", "#BC80BD", "#CCEBC5", "#FFED6F",
# "#7FC97F", "#BEAED4", "#FDC086", "#E6AB02", "#386CB0", "#A6761D", "#F0027F", "#BF5B17", "#666666", "#1B9E77", "#D95F02",
# "#7570B3", "#E7298A", "#66A61E", "#FFFF99", "#BEBADA")
#
#Import of the gene information
# DBconnection <- dbConnect(RSQLite::SQLite(),
# dbname = "DB_GeneExpressionV2.db")
geneData <- reactive({
gene <- as.character(input$gene)
gene <- gsub("-", "_", gene) # '-' creates issues when calling database so '-' were replaced by "_" in the database's names
#gene <- gsub("\\.", "_", gene) # '.' creates issues when calling database so '-' were replaced by "_" in the database's names
# #SQL databases
# a <- dbGetQuery(DBconnection, paste("SELECT * FROM", gene, sep = " "))
#RDS files local
# a <- readRDS(paste("/genedata/home/arthur/Documents/GTEx/shiftingLM_genes/shiny_app/RDS files/DB_GeneExpressionV2/",
# gene, ".RDS", sep = ""))
#RDS files online
a <- readRDS(paste("data/DB_GeneExpression_correctGeneSymbol/",
gene, ".RDS", sep = ""))
a
})
#Database for the peak enrichment data
# DBconnection2 <- dbConnect(RSQLite::SQLite(),
# dbname = "DB_PeakEnrichment.db")
# GENE SECTION ------------------------------------------------------------
##SIDEBAR
#Update gene List and tissue List
observe({
updatePickerInput(session, "gene",
choices = as.character(geneList$gene)[order(as.character(geneList$gene))],
selected = "CDKN2A")
})
observe({
gene <- as.character(req(input$gene))
#Keep the selected tissue if the new gene is expressed in it
#Otherwise, put the heatmpa wil all tissues
if (input$tissue %in% as.character(geneList$tissue[[match(gene, geneList$gene)]]))
{
selected <- input$tissue
} else
{
selected <- "All tissues"
}
updatePickerInput(session, "tissue",
choices = c("All tissues", as.character(geneList$tissue[[match(gene, geneList$gene)]])[order(as.character(geneList$tissue[[match(gene, geneList$gene)]]))]),
selected = selected)
updateAwesomeRadio(session, "coloredBy", choices = list("All" = "none", "Sex" = "Sex"), selected = "none",
inline = T, checkbox = TRUE)
updateAwesomeRadio(session, "shapedBy", choices = list("All" = "none", "Condition*" = "Condition"), selected = "none",
inline = T, checkbox = TRUE)
})
#Update condition list
output$shapedByCondition <- renderUI({
condition <- colnames(donorCondition)[-1][order(colnames(donorCondition)[-1])]
subtext <- conditionID$ID[match(condition, conditionID$description)]
pickerInput("condition", "Select:",
choices = condition,
choicesOpt = list(subtext = subtext),
options = list(`live-search` = TRUE))
})
#table Kruskal-Wallis test when condition is checked
output$KruskalWallisCondition <- DT::renderDataTable({
tissue <- input$tissue
#when a new gene is selected, geneData is updated sooner than input$tissue generating an error message
validate(need(nrow(geneData()[geneData()$tissue == input$tissue, ]) != 0, "")) #allow to hide the error message
tmp <- geneData()[geneData()$tissue == tissue,]
temp <- data.frame(SAMPID = tmp$samp_id, expression = tmp$expression)
temp <- cbind(temp, donorCondition[match(temp$SAMPID, donorCondition$SAMPID), -1])
tmp <- data.frame()
for (i in 3:ncol(temp))
{
if (length(temp$expression[temp[,i] %in% c(0,1)])!=0 & length(unique(temp[,i][temp[,i] %in% c(0,1)])) == 2)
{
tmp <- rbind(tmp, data.frame(condition = colnames(temp)[i],
pvalue = kruskal.test(temp$expression[temp[,i] %in% c(0,1)], temp[,i][temp[,i] %in% c(0,1)])$p.value))
}
}
tmp$padj <- p.adjust(tmp$pvalue, method = "BH")
tmp$conditionID <- conditionID$ID[match(tmp$condition, conditionID$description)]
tmp$pvalue <- round(tmp$pvalue, 4)
tmp$padj <- round(tmp$padj, 4)
tmp <- tmp[order(tmp$padj),]
condition <- ifelse(identical(as.character(input$shapedBy) == "Condition" & !is.na(input$condition), logical(0)) | as.character(input$shapedBy) == "none", "none", as.character(input$condition))
validate(need(condition %in% colnames(donorCondition), ""))
condition <- conditionID$ID[match(condition, conditionID$description)]
DT::datatable(tmp[, c("conditionID", "pvalue", "padj", "condition")],
escape = F,
selection = list(mode = "none"),
colnames = c("Condition ID", "p-value", "adjusted p-value", "condition"),
rownames = F,
options = list(deferRender = TRUE, scrollY = 400, scroller = TRUE, scollX = T,
rowCallback = JS(
"function(nRow, aData, iDisplayIndex, iDisplayIndexFull) {",
"var full_text = aData[3]",
"$('td:eq(0)', nRow).attr('title', full_text);",
"}"),
columnDefs = list(list(visible=FALSE, targets=c(3)),
list(className = 'dt-center', targets = 1:3))
),
extensions = "Scroller"
)
# #Not working with rowCallback
# %>% DT::formatStyle("conditionID", 'pvalue',
# color = DT::styleInterval(cuts = c(0.05), values = c('tomato', 'black'))
# ) %>% DT::formatStyle("conditionID", 'padj',
# fontWeight = DT::styleInterval(cuts = c(0.05), values = c('bold', 'normal'))
# ) %>% DT::formatStyle(
# "conditionID", target = 'row', backgroundColor = DT::styleEqual(levels = condition, values = "yellow")
# )
})
##GLOBAL HEATMAP
#Profile
output$Heatmap_LoessGEvsAge <- renderHighchart({
gene <- input$gene
# Images not working
# title <- paste(gene, " ",
# "<a href='https://www.ncbi.nlm.nih.gov/gene/?term=", gene, "' target='_blank'> <img src='NCBI.png' title='NCBI' height='30px' style='padding-bottom:5px;'/></a>",
# "<a href='http://www.genecards.org/cgi-bin/carddisp.pl?gene=", gene, "' target='_blank'> <img src='geneCards.png' title='GeneCards' height='30px' style='padding-bottom:5px;'/></a>",
# sep = "")
title <- paste(gene, " ",
"<a href='https://www.ncbi.nlm.nih.gov/gene/?term=", gene, "' target='_blank'>NCBI</a>",
" | ",
"<a href='http://www.genecards.org/cgi-bin/carddisp.pl?gene=", gene, "' target='_blank'>GeneCards</a>",
sep = "")
#The gene list is loaded faster that the tissue list. In the meantime, an error message appears since no tissue is selcted
validate(need(input$tissue != "", "")) #avoid the error message
g <- Heatmap_LoessGEvsAge(geneData())
g %>%
hc_title(text = title,
useHTML = T) %>%
hc_exporting(enabled = T,
filename = paste("voyAGEr_Profile_", gene, "_acrossTissues"),
buttons = list(contextButton = list(align = "left",
symbolStrokeWidth = 4,
symbolSize = 20,
symbolStroke = '#4D4D4D',
symbol = "menu")))
})
#Alterations
output$Heatmap_signficanceAlterationsvsAge <- renderHighchart({
gene <- input$gene
variable <- input$variable_Gene_Alteration
variable <- ifelse(variable == "Age", "Age", ifelse(variable == "Gender", "Sex", "Age&Sex"))
# title <- paste(gene, " ",
# "<a href='https://www.ncbi.nlm.nih.gov/gene/?term=", gene, "' target='_blank'> <img src='NCBI.png' title='NCBI' height='30px' style='padding-bottom:5px;'/></a>",
# "<a href='http://www.genecards.org/cgi-bin/carddisp.pl?gene=", gene, "' target='_blank'> <img src='geneCards.png' title='GeneCards' height='30px' style='padding-bottom:5px;'/></a>",
# sep = "")
title <- paste(gene, " ",
"<a href='https://www.ncbi.nlm.nih.gov/gene/?term=", gene, "' target='_blank'>NCBI</a>",
" | ",
"<a href='http://www.genecards.org/cgi-bin/carddisp.pl?gene=", gene, "' target='_blank'>GeneCards</a>",
sep = "")
validate(need(input$tissue != "", "")) #avoid the error message
g <- Heatmap_signficanceAlterationsvsAge(p_Alterations())
g %>%
hc_title(text = title,
useHTML = T) %>%
hc_exporting(enabled = T,
filename = paste("voyAGEr_Alteration_", gene, "_across_", variable, sep = ''),
buttons = list(contextButton = list(align = "left",
symbolStrokeWidth = 4,
symbolSize = 20,
symbolStroke = '#4D4D4D',
symbol = "menu")))
})
##GENE-SPECIFIC
#PROFILE
#Scatter plot
output$scatterGEvsAge <- renderHighchart({
gene <- as.character(input$gene)
tissue <- as.character(input$tissue)
colored <- input$coloredBy
geneInfo <- geneList$info[match(gene, geneList$gene)]
condition <- ifelse(identical(as.character(input$shapedBy) == "Condition" & !is.na(input$condition), logical(0)) | as.character(input$shapedBy) == "none", "none", as.character(input$condition))
#when a new gene is selected, geneData is updated sooner than input$tissue generating an error message
validate(need(nrow(geneData()[geneData()$tissue == input$tissue, ]) != 0, "")) #allow to hide the error message
#Title woth logo linking to genecards and NCBI websites
# title <- paste(gene, " ",
# "<a href='https://www.ncbi.nlm.nih.gov/gene/?term=", gene, "' target='_blank'> <img src='NCBI.png' title='NCBI' height='30px' style='padding-bottom:5px;'/></a>",
# "<a href='http://www.genecards.org/cgi-bin/carddisp.pl?gene=", gene, "' target='_blank'> <img src='geneCards.png' title='GeneCards' height='30px' style='padding-bottom:5px;'/></a>",
# sep = "")
title <- paste(gene, " ",
"<a href='https://www.ncbi.nlm.nih.gov/gene/?term=", gene, "' target='_blank'>NCBI</a>",
" | ",
"<a href='http://www.genecards.org/cgi-bin/carddisp.pl?gene=", gene, "' target='_blank'>GeneCards</a>",
sep = "")
g <- scatter_GEvsAge(geneData(), tissue, colored = colored, shaped = condition,
donorCondition = donorCondition, gene = gene, geneInfo = geneInfo)
g %>%
hc_title(text = title,
useHTML = T) %>%
hc_exporting(enabled = T,
filename = paste("voyAGEr_Profile_", gene, "_", tissue, sep = ''),
buttons = list(contextButton = list(align = "left",
symbolStrokeWidth = 4,
symbolSize = 20,
symbolStroke = '#4D4D4D',
symbol = "menu")))
})
#Data table gene expression and donor information
output$geneExpression <- DT::renderDataTable({
gene <- as.character(input$gene)
#gene <- gsub("-", "_", gene) # '-' creates issues when calling database so '-' were replaced by "_" in the database's names
#gene <- gsub("\\.", "_", gene) # '.' creates issues when calling database so '-' were replaced by "_" in the database's names
tissue <- as.character(input$tissue)
ymin <- ifelse(input$Selectedymin == "reset", input$Selectedymin, as.numeric(input$Selectedymin))
ymax <- ifelse(input$Selectedymax == "reset", input$Selectedymax, as.numeric(input$Selectedymax))
xmin <- ifelse(input$Selectedxmin == "reset", input$Selectedxmin, as.numeric(input$Selectedxmin))
xmax <- ifelse(input$Selectedxmax == "reset", input$Selectedxmax, as.numeric(input$Selectedxmax))
selectedPoint <- ifelse(is.null(input$ClickedStatus), "select", input$ClickedStatus)
#selectedPoint <- "select" #remove possiblity of choosing a single point
#To add this option
#1. uncomment the previous selectedPoint
#2. assign the value TRUE to allowPointSelect in the scatter_GEvsAge function
#3. uncomment the events = list(click = ClickFunction) in the scatter_GEvsAge function
indexPoint <- input$ClickedIndex + 1 #JS starts counting at 0
condition <- ifelse(identical(as.character(input$shapedBy) == "Condition" & !is.na(input$condition), logical(0)) | as.character(input$shapedBy) == "none", "none", as.character(input$condition))
#when a new gene is selected, geneData is updated sooner than input$tissue generating an error message
validate(need(nrow(geneData()[geneData()$tissue == input$tissue, ]) != 0, "")) #allow to hide the error message
if (condition == "none")
{
datatable_donorInfo(geneData(), tissue, selectedPoint, xmin, xmax, ymin, ymax, indexPoint, donorCondition = donorCondition, conditionID)
} else
{
datatable_donorInfo(geneData(), tissue, selectedPoint, xmin, xmax, ymin, ymax, indexPoint, donorCondition = donorCondition, conditionID) %>%
DT::formatStyle(condition, backgroundColor = "lightsalmon")
}
})
#Table downloading
#Preparation of the table to download
output$geneExpressionDownload <- DT::renderDataTable({
tissue <- as.character(input$tissue)
gene <- input$gene
tmp <- geneData()
tmp <- tmp[tmp$tissue == tissue,]
tmp$sex[tmp$sex == 1] <- "Male"
tmp$sex[tmp$sex == 2] <- "Female"
#Change age format to give an interval and not the exact age
tmp$age <- as.character(cut(tmp$age, breaks = seq(20,70, by = 5), include.lowest = T))
#Add and rename condition
temp <- donorCondition[match(tmp$samp_id, donorCondition$SAMPID), -1]
temp[is.na(temp)] <- "Unknown"
temp[temp == 96] <- "Unknown"
temp[temp == 97] <- "Unknown"
temp[temp == 99] <- "Unknown"
temp[temp == 1] <- "Positive"
temp[temp == 0] <- "Negative"
tmp <- tmp[, c("samp_id", "age", "expression", "sex")]
colnames(tmp) <- c("GTEx sample ID", "Age (years)", "Gene Expression (log(CPM))", "Sex of the donor")
tmp <- cbind(tmp, temp)
rownames(tmp) <- 1:nrow(tmp)
filename <- paste("voyAGEr_GEdata_", gene, "_", tissue, sep = '')
DT::datatable(tmp,
escape = F,
options = list(dom = "B",
pageLength = nrow(tmp),
buttons = list(list(extend='copy',
filename = filename),
list(extend='csv',
filename = filename),
list(extend='excel',
filename= filename)),
columnDefs = list(list(visible=FALSE, targets = 0:ncol(tmp))),
headerCallback = JS(
"function( thead, data, start, end, display ) {
$(thead).closest('thead').find('th').each(function(){
$(this).css('color', 'red').css('border','none');
});
}"
),
initComplete = JS(
"function(settings) {
var table = settings.oInstance.api();
$(table.table().node()).removeClass('no-footer');
}")),
extensions = "Buttons"
)
})
#ALTERATIONS
output$Line_signficanceAlterationsvsAge <- renderHighchart({
#when a new gene is selected, geneData is updated sooner than input$tissue generating an error message
validate(need(nrow(geneData()[geneData()$tissue == input$tissue, ]) != 0, "")) #allow to hide the error message
gene <- input$gene
variable <- input$variable_Gene_Alteration
tissue <- input$tissue
validate(need(!is.null(tissue) & tissue != "" & tissue != "All tissues", ""))
pvalueData <- p_Alteration_gene()
statsAllAges <- Sig_Mag_Gene_perTissueVariable()[Sig_Mag_Gene_perTissueVariable()$gene==gene,]
ablineAllAges <- fit_abline()[fit_abline()$gene==gene,]
# title <- paste(gene, " ",
# "<a href='https://www.ncbi.nlm.nih.gov/gene/?term=", gene, "' target='_blank'> <img src='NCBI.png' title='NCBI' height='30px' style='padding-bottom:5px;'/></a>",
# "<a href='http://www.genecards.org/cgi-bin/carddisp.pl?gene=", gene, "' target='_blank'> <img src='geneCards.png' title='GeneCards' height='30px' style='padding-bottom:5px;'/></a>",
# sep = "")
title <- paste(gene, " ",
"<a href='https://www.ncbi.nlm.nih.gov/gene/?term=", gene, "' target='_blank'>NCBI</a>",
" | ",
"<a href='http://www.genecards.org/cgi-bin/carddisp.pl?gene=", gene, "' target='_blank'>GeneCards</a>",
sep = "")
validate(need(!is.null(pvalueData), "No possible analysis for this alteration in this tissue"))
variable <- ifelse(variable == "Age", "Age", ifelse(variable == "Gender", "Sex", "Age&Sex")) #change name for download filename
g <- Line_signficanceAlterationsvsAge(gene, pvalueData, geneData = geneData(), allAges = statsAllAges, abline=ablineAllAges, tissue=tissue, coloredBy = variable) %>%
hc_title(text = title, useHTML = T) %>%
hc_exporting(enabled = T,
filename = paste("voyAGEr_Alteration_", gene, "_across_", variable, "_", tissue, sep = ''),
buttons = list(contextButton = list(align = "left",
symbolStrokeWidth = 4,
symbolSize = 20,
symbolStroke = '#4D4D4D',
symbol = "menu")))
})
# TISSUE SECTION ----------------------------------------------------------
##GLOBAL HEATMAP
output$AgeWavesOrganism <- renderHighchart({
variable <- input$variable_model_2
updatePickerInput(session, inputId = "tissue_2",
choices = c("All tissues", rownames(AgeWavesList[[variable]])[order(rownames(AgeWavesList[[variable]]))]),
selected = "All tissues")
g <- Heatmap_log10FDRvsAge(variable = variable, AgeWaves = AgeWavesList)
variable <- ifelse(variable == "Age", "Age", ifelse(variable == "Gender", "Sex", "Age&Sex")) #change name for download filename
g %>%
hc_exporting(enabled = T,
filename = paste("voyAGEr_Alteration_across_", variable, sep = ''),
buttons = list(contextButton = list(align = "left",
symbolStrokeWidth = 4,
symbolSize = 20,
symbolStroke = '#4D4D4D',
symbol = "menu")))
})
##TISSUE_SPECIFIC PEAKS
#Histogram distribution samples for chosen tissue
output$Histogram_DistributionSample <- renderHighchart({
tissue <- input$tissue_2
# #SQL database
# gene <- dbGetQuery(DBconnection, paste("SELECT * FROM", "PGD", sep = " ")) #gene PGD chosen since expressed in all tisssue
# #RDS files
# gene <- readRDS(paste("/genedata/home/arthur/Documents/GTEx/shiftingLM_genes/shiny_app/RDS files/DB_GeneExpressionV2/",
# "PGD", ".RDS", sep = ""))
#RDS files online
gene <- readRDS(paste("data/DB_GeneExpression_correctGeneSymbol/",
"PGD", ".RDS", sep = ""))
validate(need(tissue != "" & tissue != "All tissues", ""))
Histogram_DistributionSample(tissue, gene)
})
#% significance gene altered = f(age)
output$SigvsAge <- renderHighchart({
variable <- input$variable_model_2
tissue <- input$tissue_2
validate(need(tissue != "All tissues" & tissue != "", ""))
validate(need(nrow(peak[peak$tissue == tissue & peak$variable == variable,]) != 0, "No analysis for this tissue and variable"))
g <- Line_sigGenesvsAge(tissue, variable, peak)
variable <- ifelse(variable == "Age", "Age", ifelse(variable == "Gender", "Sex", "Age&Sex")) #change name for download filename
g %>%
hc_exporting(enabled = T,
filename = paste("voyAGEr_%genesAltered_across_", variable, "_", tissue, sep = ''),
buttons = list(contextButton = list(align = "right",
symbolStrokeWidth = 4,
symbolSize = 20,
symbolStroke = '#4D4D4D',
symbol = "menu")))
})
#Data table of the gene differential expression signgificance
output$genePeakTable <- DT::renderDataTable(server = FALSE,{
validate(need(!is.null(input$peakClicked), "")) # A peak must be chosen
tissue <- input$tissue_2
variable <- input$variable_model_2
peakClicked <- input$peakClicked
validate(need(!is.na(match(peakClicked, colnames(p()))), "")) # Matching column between age and peak must be found (avoid error when change tissue)
validate(need(input$peakClickedVariable == variable, "")) #When a peak is clicked and the variable is changed, enable to remove the table while no peak is selected from the new polot
tmp <- data.frame(gene = as.character(rownames(p())),
pvalue = round(p()[, match(peakClicked, colnames(p()))], 6))
tmp <- tmp[order(tmp$pvalue),]
rownames(tmp) <- 1:nrow(tmp)
tmp$Info <- paste(paste0("<a href='http://www.genecards.org/cgi-bin/carddisp.pl?gene=", tmp$gene,"' target='_blank'>", "GeneCards", "</a>"),
paste0("<a href='https://www.ncbi.nlm.nih.gov/gene/?term=", tmp$gene,"' target='_blank'>", "NCBI", "</a>"), sep = ", ")
filename <- paste("DEG_across_", variable, "_", tissue, "_", peakClicked, "yo", sep = "")
DT::datatable(tmp,
escape = F,
caption = "Significance for gene expression alteration",
selection = "single", #only one row selected at a time
#filter = "top", #can filter the results per column
options = list(deferRender = FALSE, scrollY = 600, scroller = TRUE, scollX = T,
dom = "Bfti",
buttons = list(list(extend='copy',
filename = filename,
exportOptions = list(modifier = list(page = "all"))),
list(extend='csv',
filename = filename,
exportOptions = list(modifier = list(page = "all"))),
list(extend='excel',
filename= filename,
exportOptions = list(modifier = list(page = "all"))))),
colnames = c("Gene", "p-value", "Info"),
rownames = T,
extensions = c("Scroller", "Buttons")
)
})
#Name of the selected gene based on the chosen peak
selectedGene <- reactive({
peakClicked <- input$peakClicked
indexRowClicked <- input$genePeakTable_rows_selected
validate(need(!is.na(match(peakClicked, colnames(p()))), ""))
tmp <- data.frame(gene = as.character(rownames(p())),
pvalue = round(p()[, match(peakClicked, colnames(p()))], 6))
tmp <- tmp[order(tmp$pvalue),]
gene <- as.character(tmp$gene[indexRowClicked])
gene <- ifelse(!is.character(gene), NULL, gene)
})
#Import of the gene information for the chosen gene in Tissue tab
geneData_Tissue <- reactive({
gene <- selectedGene()
gene <- gsub("-", "_", gene) # to match way the data was stored
# #SQL database
# a <- dbGetQuery(DBconnection, paste("SELECT * FROM", gene, sep = " "))
#RDS files local
# a <- readRDS(paste("/genedata/home/arthur/Documents/GTEx/shiftingLM_genes/shiny_app/RDS files/DB_GeneExpressionV2/",
# gene, ".RDS", sep = ""))
#RDS file onlibe
a <- readRDS(paste("data/DB_GeneExpression_correctGeneSymbol/",
gene, ".RDS", sep = ""))
a
})
#Plot of the Lm pvalues over age
output$Line_pvaluevsAge <- renderHighchart({
validate(need(nrow(peak[peak$tissue == input$tissue_2 & peak$variable == input$variable_model_2,]) != 0, ""))
validate(need((input$peakClickedState == 'hover' || input$peakClickedState == '') & input$variable_model_2 == input$peakClickedVariable, "Select a peak"))
validate(need(!is.na(selectedGene()), "Select a gene"))
validate(need(input$peakClickedVariable == input$variable_model_2, "")) #When a peak is clicked and the variable is changed, enable to remove the plot while no peak is selected from the new polot
tissue <- input$tissue_2
gene <- selectedGene()
pvalueData <- p()
coloredBy <- input$variable_model_2
geneInfo <- geneList$info[match(gene, geneList$gene)]
variable <- input$variable_model_2
variable <- ifelse(variable == "Age", "Age", ifelse(variable == "Gender", "Sex", "Age&Sex")) #change name for download filename
statsAllAges <- Sig_Mag_Gene_perTissueVariable_2()[Sig_Mag_Gene_perTissueVariable_2()$gene==gene,]
ablineAllAges <- fit_abline_2()[fit_abline_2()$gene==gene,]
g <- Line_pvaluevsAge(gene = gene, pvalueData = pvalueData, geneData = geneData_Tissue(), allAges = statsAllAges, abline=ablineAllAges, tissue = tissue, coloredBy = coloredBy) %>%
hc_title(text = gene) #%>%
#hc_subtitle(text = geneInfo)
g %>%
hc_exporting(enabled = T,
filename = paste("voyAGEr_Alteration_across_", variable, "_", gene, "_", tissue, sep = ''),
buttons = list(contextButton = list(align = "left",
symbolStrokeWidth = 4,
symbolSize = 20,
symbolStroke = '#4D4D4D',
symbol = "menu")))
})
##TISSUE_SPECIFIC ENRICHMENT
output$pathwaySpecific <- DT::renderDataTable({
tissue <- input$tissue_2
variable <- input$variable_model_2
#Call to the databse
modifiedTissuename <- gsub("-", "_", tissue)
modifiedTissuename <- gsub(" ", "", modifiedTissuename)
modifiedTissuename <- gsub("\\(", "", modifiedTissuename)
modifiedTissuename <- gsub("\\)", "", modifiedTissuename)
# #SQL database
# enrich <- dbGetQuery(DBconnection2, paste("SELECT * FROM", modifiedTissuename, sep = " "))
#RDS file local
# enrich <- readRDS(paste("/genedata/home/arthur/Documents/GTEx/shiftingLM_genes/shiny_app/RDS files/DB_PeakEnrichment.db/",
# modifiedTissuename, ".RDS", sep = ""))
#RDS files online
enrich <- readRDS(paste("data/DB_PeakEnrichment.db/",
modifiedTissuename, ".RDS", sep = ""))
pathway <- unique(enrich$pathway[enrich$variable == variable])
pathway <- pathway[order(as.character(pathway))]
DT::datatable(as.data.frame(gsub("REACTOME_", "", pathway)),
escape = F,
colnames = c(""),
options = list(deferRender = TRUE, scrollY = 400, scroller = TRUE, scollX = T,
rowCallback = JS(
"function(nRow, aData, iDisplayIndex, iDisplayIndexFull) {",
"var full_text = aData[0]",
"$('td:eq(0)', nRow).attr('title', full_text);",
"}")),
selection = list(mode = "multiple",
selected = 1),
rownames = F,
extensions = "Scroller"
)
})
pathwaySelected <- reactive({
tissue <- input$tissue_2
variable <- input$variable_model_2
#Call to the databse
modifiedTissuename <- gsub("-", "_", tissue)
modifiedTissuename <- gsub(" ", "", modifiedTissuename)
modifiedTissuename <- gsub("\\(", "", modifiedTissuename)
modifiedTissuename <- gsub("\\)", "", modifiedTissuename)
# #SQl database
# enrich <- dbGetQuery(DBconnection2, paste("SELECT * FROM", modifiedTissuename, sep = " "))
# #RDS file local
# enrich <- readRDS(paste("/genedata/home/arthur/Documents/GTEx/shiftingLM_genes/shiny_app/RDS files/DB_PeakEnrichment.db/",
# modifiedTissuename, ".RDS", sep = ""))
#RDS files onlibe
enrich <- readRDS(paste("data/DB_PeakEnrichment.db/",
modifiedTissuename, ".RDS", sep = ""))
pathway <- unique(enrich$pathway[enrich$variable == variable])
pathway <- pathway[order(as.character(pathway))]
pathway[input$pathwaySpecific_rows_selected]
})
#Pathway-specific NES = f(age)
output$EnrichmentAllOrSpecific <- renderUI({
tagList(
awesomeRadio(inputId = "EnrichmentAllOrSpecific", label = "Pathway", inline = T,
choices = c("All pathways", "Select:"), checkbox = T),
conditionalPanel(condition = "input.EnrichmentAllOrSpecific == 'Select:'",
div(DT::dataTableOutput("pathwaySpecific"), style = "font-size: 70%; width: 100%",server = F)
)
)
})
#Heatmap fo the NES for a given tissue adn variable
output$Heatmap_NESAgevsPathway <- renderCombineWidgets({
tissue <- input$tissue_2
variable <- input$variable_model_2
pathway <- input$EnrichmentAllOrSpecific
#Call to the databse
modifiedTissuename <- gsub("-", "_", tissue)
modifiedTissuename <- gsub(" ", "", modifiedTissuename)
modifiedTissuename <- gsub("\\(", "", modifiedTissuename)
modifiedTissuename <- gsub("\\)", "", modifiedTissuename)
# #SQL databasle
# enrich <- dbGetQuery(DBconnection2, paste("SELECT * FROM", modifiedTissuename, sep = " "))
# #RDs file local
# enrich <- readRDS(paste("/genedata/home/arthur/Documents/GTEx/shiftingLM_genes/shiny_app/RDS files/DB_PeakEnrichment.db/",
# modifiedTissuename, ".RDS", sep = ""))
#RDS files online
enrich <- readRDS(paste("data/DB_PeakEnrichment.db/",
modifiedTissuename, ".RDS", sep = ""))
SigPeak <- peak[peak$tissue == tissue & peak$variable == variable, ]
validate(need(!is.null(pathway), ""))
#Which patwhay tp show
if (pathway == "Select:")
{
validate(need(length(pathwaySelected())!=0, "Choose pathway(s) of interest"))
}
if (pathway == "All pathways")
{
pathway <- TRUE
} else
{
enrich <- enrich[enrich$pathway %in% pathwaySelected(), ]
pathway <- FALSE
}
validate(need(length(which(SigPeak$sig == "sig")) != 0, "No significant peak or analysis done for this tissue and variable"))
if (pathway == TRUE)
{
validate(need(length(enrich$pathway[which(enrich$padj <= 0.05 & enrich$age %in% SigPeak$age[SigPeak$sig == "sig"])]) != 0 , "No significant enrichment"))
}
g <- Heatmap_NESAgevsPathway(peak = peak, tissue = tissue, variable = variable, enrichment = enrich, Cluster_Reactome = Cluster_Reactome, ALL = pathway)
variable <- ifelse(variable == "Age", "Age", ifelse(variable == "Gender", "Sex", "Age&Sex")) #change name for download filename
g
})
#family presentation
output$Heatmap_family <- renderHighchart({
#To be linked with the enrichment heatmap, the family presentation only occurs when the heatmap is shown
tissue <- input$tissue_2
variable <- input$variable_model_2
#Call to the databse
modifiedTissuename <- gsub("-", "_", tissue)
modifiedTissuename <- gsub(" ", "", modifiedTissuename)
modifiedTissuename <- gsub("\\(", "", modifiedTissuename)
modifiedTissuename <- gsub("\\)", "", modifiedTissuename)
# #SQL database
# enrich <- dbGetQuery(DBconnection2, paste("SELECT * FROM", modifiedTissuename, sep = " "))
# #RDS file local
# enrich <- readRDS(paste("/genedata/home/arthur/Documents/GTEx/shiftingLM_genes/shiny_app/RDS files/DB_PeakEnrichment.db/",
# modifiedTissuename, ".RDS", sep = ""))
#RDS files online
enrich <- readRDS(paste("data/DB_PeakEnrichment.db/",
modifiedTissuename, ".RDS", sep = ""))
SigPeak <- peak[peak$tissue == tissue & peak$variable == variable, ]
validate(need(length(which(SigPeak$sig == "sig")) != 0, ""))
validate(need(length(enrich$pathway[which(enrich$padj <= 0.05 & enrich$age %in% SigPeak$age[SigPeak$sig == "sig"])]) != 0, ""))
Heatmap_family(Cluster_Reactome)
})
output$wordcloud_family <- renderHighchart({
#To be linked with the enrichment heatmap, the family presentation only occurs when the heatmap is shown
tissue <- input$tissue_2
variable <- input$variable_model_2
#Call to the databse
modifiedTissuename <- gsub("-", "_", tissue)
modifiedTissuename <- gsub(" ", "", modifiedTissuename)
modifiedTissuename <- gsub("\\(", "", modifiedTissuename)
modifiedTissuename <- gsub("\\)", "", modifiedTissuename)
# #SQL database
# enrich <- dbGetQuery(DBconnection2, paste("SELECT * FROM", modifiedTissuename, sep = " "))
#RDS file local
# enrich <- readRDS(paste("/genedata/home/arthur/Documents/GTEx/shiftingLM_genes/shiny_app/RDS files/DB_PeakEnrichment.db/",
# modifiedTissuename, ".RDS", sep = ""))
#RDS files online
enrich <- readRDS(paste("data/DB_PeakEnrichment.db/",
modifiedTissuename, ".RDS", sep = ""))
SigPeak <- peak[peak$tissue == tissue & peak$variable == variable, ]
validate(need(length(which(SigPeak$sig == "sig")) != 0, ""))
validate(need(length(enrich$pathway[which(enrich$padj <= 0.05 & enrich$age %in% SigPeak$age[SigPeak$sig == "sig"])]) != 0, ""))
validate(need(!is.null(input$familyClicked), "Select a family"))
wordcloud_family(Cluster_Reactome_affiliation, family = input$familyClicked) %>%
hc_exporting(enabled = T,
filename = paste("voyAGEr_WordCloud_family-", input$familyClicked, sep = ''),
buttons = list(contextButton = list(align = "left",
symbolStrokeWidth = 4,
symbolSize = 20,
symbolStroke = '#4D4D4D',
symbol = "menu")))
})
output$listPathway_family <- DT::renderDataTable({
#To be linked with the enrichment heatmap, the family presentation only occurs when the heatmap is shown
tissue <- input$tissue_2
variable <- input$variable_model_2
#Call to the databse
modifiedTissuename <- gsub("-", "_", tissue)
modifiedTissuename <- gsub(" ", "", modifiedTissuename)
modifiedTissuename <- gsub("\\(", "", modifiedTissuename)
modifiedTissuename <- gsub("\\)", "", modifiedTissuename)
# #SQL database
# enrich <- dbGetQuery(DBconnection2, paste("SELECT * FROM", modifiedTissuename, sep = " "))
#RDS file local
# enrich <- readRDS(paste("/genedata/home/arthur/Documents/GTEx/shiftingLM_genes/shiny_app/RDS files/DB_PeakEnrichment.db/",
# modifiedTissuename, ".RDS", sep = ""))
#RDS files online
enrich <- readRDS(paste("data/DB_PeakEnrichment.db/",
modifiedTissuename, ".RDS", sep = ""))
SigPeak <- peak[peak$tissue == tissue & peak$variable == variable, ]
validate(need(length(which(SigPeak$sig == "sig")) != 0, ""))
validate(need(length(enrich$pathway[which(enrich$padj <= 0.05 & enrich$age %in% SigPeak$age[SigPeak$sig == "sig"])]) != 0, ""))
validate(need(!is.null(input$familyClicked), "Select a family"))
# tmp <- rbind(data.frame(pathway = Cluster_Reactome_affiliation[[input$familyClicked]][!is.na(Cluster_Reactome_affiliation[[input$familyClicked]][,1]),1]),
# data.frame(pathway = Cluster_Reactome_affiliation[[input$familyClicked]][!is.na(Cluster_Reactome_affiliation[[input$familyClicked]][,2]),2]))
tmp <- as.data.frame(as.matrix(c(Cluster_Reactome_affiliation[[input$familyClicked]]$REACTOME.pathways,Cluster_Reactome_affiliation[[input$familyClicked]]$KEGG.GO.pathways),ncol=2))
filename <- paste("voyAGEr_WordCloud_family-", input$familyClicked, sep = '')
DT::datatable(tmp,
escape = F,
selection = list(mode = "none"),
colnames = paste("Family", input$familyClicked),
rownames = F,
options = list(deferRender = TRUE, scrollY = 270, scroller = TRUE, scollX = T,
buttons = list(list(extend='copy',
filename = filename),
list(extend='csv',