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genesetmodule.R
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###########################################################################################################
## Omics Visualization R Shiny App
##
##This software belongs to Biogen Inc. All right reserved.
##
##@file: genesetmodule.R
##@Developer : Benbo Gao (benbo.gao@Biogen.com); Xinmin Zhang (xinmin@bioinforx.com)
##@Date : 7/3/2023
##@version 3.0
##########################################################################################################
## Gene Set Enrichment
##########################################################################################################
# pkgs: "pathview", "biomaRt", "ComplexHeatmap", "DT", "stringr", "dplyr", "tidyr"
# this module require results_long, tests, ProteinGeneName, Species, data_long(for heatmap)
library(tibble)
library(pathview)
library(biomaRt)
#library(enrichplot)
#library(enrichR)
library(ComplexHeatmap)
library(fgsea)
#library(wikiprofiler)
library(svgPanZoom)
source("wikiprofiler_Fixed.R")
library(org.Hs.eg.db); library(org.Mm.eg.db); library(org.Rn.eg.db)
#Use metabaser only when the gmt file exists
if (file.exists("db/human/metabase_maps_genesymbols.gmt")) {
library(metabaser)
#Now launch metabaser and connect to database
if (!metabase.alive()){
library(metabaser)
load("db/metabase_config.RData")
metabase.connect(dbname, uid, pwd, host=host, port=port, type=type, driver=driver)
}
MetabaseOutput <- function(outputId, width = "100%", height = "1200px") {
htmlwidgets::shinyWidgetOutput(outputId, "cyBasicMap", width, height, package = "metabaser")
}
renderMetabase <- function(expr, env = parent.frame(), quoted = FALSE) {
if (!quoted) { expr <- substitute(expr) } # force quoted
htmlwidgets::shinyRenderWidget(expr, "cyBasicMapOutput", env, quoted = TRUE)
}
}
ORAEnrichment <- function(deGenes,universe, gsets, logFC, Dir="Both"){
deGenes = deGenes[which(deGenes %in% universe)]
tmp = rep(NA, length(gsets))
#ora.stats = data.frame(p.value=tmp, p.adj = tmp, DeGeneNum=tmp,UpGene= tmp, DownGene=tmp, SetNum = tmp, N_q=tmp, SetNumAll=tmp, DeGene_in_Set=tmp)
ora.stats = data.frame(p.value=tmp, p.adj = tmp, DeGeneNum=tmp,DE_UpGene= tmp, DE_DownGene=tmp, SetNum = tmp, N_q=tmp, Fold_Enrich=tmp,
SetNumAll=tmp, Total_DEG=tmp, Total_Gene=tmp, DeGene_in_Set=tmp)
totalDE = length(deGenes)
if (Dir=="Up") {totalDE = sum(logFC > 0)
} else if (Dir=="Down") {totalDE = sum(logFC < 0) }
n = length(universe) - totalDE
for (j in 1:length(gsets)){
gset = gsets[[j]]
DEinS = intersect(gset, deGenes)
logFCinS = logFC[DEinS]
totalDEinS = length(intersect(gset, deGenes))
totalSinUniverse = length(intersect(gset, universe))
N_q=totalDEinS- 0.5
if (Dir=="Up") {N_q=length(logFCinS[logFCinS > 0])-0.5; DEinS<-names(logFCinS[logFCinS > 0])
} else if (Dir=="Down") {N_q=length(logFCinS[logFCinS < 0])-0.5; DEinS<-names(logFCinS[logFCinS < 0]) }
ora.stats[j, "p.value"] = phyper(q = N_q, m=totalDE, n = n, k = totalSinUniverse, lower.tail = FALSE)
ora.stats[j, "DeGeneNum"] = totalDEinS
ora.stats[j, "SetNum"] = totalSinUniverse #previous versions used length(gset)
ora.stats[j, "DE_UpGene"] = length(logFCinS[logFCinS > 0])
ora.stats[j, "DE_DownGene"] = length(logFCinS[logFCinS < 0])
ora.stats[j, "N_q"]=N_q
ora.stats[j, "SetNumAll"]=length(gset)
ora.stats[j, "Fold_Enrich"]= round( (totalDEinS/totalDE) / (totalSinUniverse/length(universe) )*100)/100
ora.stats[j, "Total_DEG"]=totalDE
ora.stats[j, "Total_Gene"]=length(universe)
ora.stats[j, "DeGene_in_Set"]=paste(DEinS, collapse = ",")
}
ora.stats[, "p.adj"] = p.adjust(ora.stats[, "p.value"], method = "BH")
ora.stats[, "DE_Direction"]=Dir
ora.stats<-ora.stats%>%mutate(GeneSet= names(gsets))%>%
arrange(p.value, dplyr::desc(N_q))%>% rownames_to_column('rank')%>%dplyr::select(-N_q)%>%relocate(GeneSet)
return(ora.stats)
}
geneset_ui <- function(id) {
ns <- shiny::NS(id)
fluidRow(
rclipboard::rclipboardSetup(),
column(3,
wellPanel(
uiOutput(ns('loadedprojects')),
conditionalPanel(ns = ns, "input.geneset_tabset=='Over-Representation Analysis (ORA)'",
radioButtons(ns("ORA_input_type"),label="Genes Used for ORA", choices=c("Subset from Comparison","Gene List"),inline = TRUE, selected="Subset from Comparison"),
conditionalPanel(ns = ns, "input.ORA_input_type=='Gene List'",
textAreaInput(ns("ORA_list"), "Enter Gene List", "", cols = 5, rows=6),
radioButtons(ns("ORA_universe"),label="Background Genes", choices=c("Genes in current project","Genes from Gene Sets"),inline = TRUE, selected="Genes in current project"))
),
conditionalPanel(ns = ns, "input.ORA_input_type!='Gene List' || input.geneset_tabset!='Over-Representation Analysis (ORA)' ",
selectInput(ns("geneset_test"), label="Select Comparison for Gene Set Analysis", choices=NULL),
conditionalPanel(ns = ns, "input.geneset_tabset!='MetaBase Pathway View' && input.geneset_tabset!='Wikipathways View'",
uiOutput(ns('Second_Comparison'))),
conditionalPanel(ns = ns, "input.geneset_tabset=='Over-Representation Analysis (ORA)' || input.geneset_tabset=='Gene Expression'",
column(width=6,numericInput(ns("geneset_FCcut"), label= "Fold Change Cutoff", value = 1.2, min=1, step=0.1)),
column(width=6,numericInput(ns("geneset_pvalcut"), label= "P Value Cutoff", value=0.01, min=0, step=0.001)),
radioButtons(ns("geneset_psel"), label= "P value or P.adj Value?", choices= c("Pval"="Pval","Padj"="Padj"),inline = TRUE),
radioButtons(ns("geneset_direction"), label= "Up- or Down-Regulated Genes?", choices= c("Both", "Up", "Down"),inline = TRUE),
span(textOutput(ns("filteredgene1")), style = "color:red; font-size:15px; font-family:arial; font-style:italic"),
span(textOutput(ns("filteredgene2")), style = "color:red; font-size:15px; font-family:arial; font-style:italic")
)),
radioButtons(ns("MSigDB_species"), label= "Gene Set Species",choices=c("human","mouse", "rat"), inline = TRUE, selected = "human"),
span(textOutput(ns("SpeciesGSEAInfo")), style = "color:red; font-size:13px; font-family:arial; font-style:italic"),
selectInput(ns("map_genes"), "Gene Symbol Mapping", choices = c("Homologous Genes", "Change to UPPER case (human)",
"Change to Title Case (mouse/rat)", "No Change (as it is)"), selected="Homologous Genes"),
conditionalPanel(ns = ns, "input.geneset_tabset=='Gene Set Enrichment Analysis (GSEA)' || input.geneset_tabset=='Over-Representation Analysis (ORA)' || input.geneset_tabset=='Gene Expression'",
conditionalPanel(ns = ns, "input.geneset_tabset=='Gene Set Enrichment Analysis (GSEA)'",
radioButtons(ns("gene_rank_method"), label= "Rank Genes By",choices=c("logFC","-log(P-Value)"), inline = TRUE, selected = "logFC"),
column(width=6,numericInput(ns("gsetMin"), label= "GeneSet Min Size", value = 15, min=5, step=1)),
column(width=6,numericInput(ns("gsetMax"), label= "GeneSet Max Size", value = 1000, min=100, step=1)),
sliderInput(ns("gsea_FDR"), "GSEA Adjusted P-Value Cutoff", min = 0, max = 1, step = 0.01, value = 0.25),
checkboxInput(ns("gsea_collapase"), "Collapse Gene Sets", FALSE, width="90%"),
),
conditionalPanel(ns = ns, "input.geneset_tabset=='Over-Representation Analysis (ORA)'",
sliderInput(ns("ora_pvalue"), "ORA p.adj Cutoff:", min = 0, max = 1, step = 0.01, value = 0.05),
checkboxInput(ns("ora_collapase"), "Collapse Gene Sets", FALSE, width="90%"),
),
conditionalPanel(ns = ns, "input.MSigDB_species=='human'",
checkboxGroupInput(ns("MSigDB_species_human_GSEA"), label= "Human Collections",
choices= NULL, selected = NULL) ),
conditionalPanel(ns = ns, "input.MSigDB_species=='mouse'",
checkboxGroupInput(ns("MSigDB_species_mouse_GSEA"), label= "Mouse Collections",
choices= NULL, selected = NULL) ),
conditionalPanel(ns = ns, "input.MSigDB_species=='rat'",
checkboxGroupInput(ns("MSigDB_species_rat_GSEA"), label= "Rat Collections",
choices= NULL, selected = NULL) ),
checkboxInput(ns("use_customset"), "Add Custom GeneSet", FALSE, width="90%"),
conditionalPanel(ns = ns, "input.use_customset==1",
radioButtons(ns("custom_set_option"), label= "Custom GeneSet From",choices=c("Text Box","File"), inline = TRUE, selected = "Text Box"),
conditionalPanel(ns = ns, "input.custom_set_option=='Text Box'",
textAreaInput(ns("CustomGeneset"), "Enter gene symbols", "", cols = 5, rows=6) ),
conditionalPanel(ns = ns, "input.custom_set_option=='File'",
p("Prepare your own geneset in GMT format. One geneset per row; each row has name, description, and the gene symbols in the gene set separated by tabs. Description is ignored, you can just put NA for it.",
style = "color:red; font-size:11px; font-family:arial; font-style:italic"),
tags$a(href="CustomGeneSets.gmt", "Download example custom GMT file with three human gene sets"),
fileInput(ns("custom_gmt_file"), "Choose geneset GMT file") )
)
),
conditionalPanel(ns = ns, "input.geneset_tabset=='Gene Set Heatmap'",
radioButtons(ns("gs_heatmap_DE"),label="From the Gene Set, Show",inline = FALSE, choices=c("All Genes", "DE/LeadingEdge Genes Only"),
selected="All Genes"),
column(width=6,sliderInput(ns("hxfontsize_gsh"), "Column Font Size:", min = 2, max = 24, step = 1, value = 12)),
column(width=6,sliderInput(ns("hyfontsize_gsh"), "Row Font Size:", min = 2, max = 24, step = 1, value = 10)),
column(width=6,sliderInput(ns("htfontsize_gsh"), "Title Font Size:", min = 10, max = 32, step = 1, value = 14)),
column(width=6,sliderInput(ns("hlfontsize_gsh"), "Legend Font Size:", min = 2, max = 20, step = 1, value = 10)),
radioButtons(ns("gs_heatmap_label"),label="Gene Label",inline = TRUE, choices=c("UniqueID", "Gene.Name"), selected="Gene.Name"),
sliderInput(ns("geneset_heatmap_width"), "Heatmap Width:", min = 200, max = 3000, step = 50, value = 900),
sliderInput(ns("geneset_heatmap_height"), "Heatmap Height:", min = 200, max = 3000, step = 50, value = 800)
),
conditionalPanel(ns = ns, "input.geneset_tabset=='KEGG Pathway View' || input.geneset_tabset=='MetaBase Pathway View' ",
radioButtons(ns("kegg_more_tests"), label= "Add more comparisons?", choices= c("Yes", "No"),selected="No", inline = TRUE),
conditionalPanel(ns = ns, "input.kegg_more_tests=='Yes'",
selectInput(ns("geneset_test2"), label="2nd Comparison", choices=NULL),
selectInput(ns("geneset_test3"), label="3rd Comparison", choices=NULL),
selectInput(ns("geneset_test4"), label="4th Comparison", choices=NULL),
selectInput(ns("geneset_test5"), label="5th Comparison", choices=NULL)),
conditionalPanel(ns = ns, "input.geneset_tabset=='KEGG Pathway View'",
column(width=6, selectInput(ns("kegg_logFC"), label= "Gene log2FC Range:", choices= c(0.5, 1, 2, 3), selected=1)),
column(width=6, selectInput(ns("kegg_logFC_cpd"), label= "Compound log2FC Range:", choices= c(0.5, 1, 2, 3), selected=1)),
radioButtons(ns("kegg_mapsample"), label= "Map Symbols to KEGG Nodes?", choices= c("Yes"=TRUE, "No"=FALSE),inline = TRUE)),
conditionalPanel(ns = ns, "input.geneset_tabset=='MetaBase Pathway View'",
selectInput(ns("obj_style"), label="Network Object Style", choices=c("icon", "polygon", "none"), selected="icon")),
)
)
),
column(9,
tabsetPanel(id=ns("geneset_tabset"),
tabPanel(title="Gene Set Enrichment Analysis (GSEA)",
actionButton(ns("compute_gsea"), "Compute/Refresh", style="color: #0961E3; background-color: #F6E98C ; border-color: #2e6da4"),
tags$br(),tags$hr(),
DT::dataTableOutput(ns("MSigDB_GSEA"))),
tabPanel(title="Over-Representation Analysis (ORA)",
actionButton(ns("compute_ora"), "Compute/Refresh", style="color: #0961E3; background-color: #F6E98C ; border-color: #2e6da4"),
tags$br(),tags$hr(),
conditionalPanel(ns = ns, "input.ORA_input_type!='Gene List'",
DT::dataTableOutput(ns("MSigDB_ORA"))),
conditionalPanel(ns = ns, "input.ORA_input_type=='Gene List'",
DT::dataTableOutput(ns("MSigDB_ORA_list"))) ),
# need to use label
tabPanel(title="Gene Expression", fluidRow( column(4,textInput(ns('analysis_type_1'), 'Analysis Type')%>%disabled()),
column(4,textInput(ns('x1'), 'Gene Set')) ),
conditionalPanel(ns = ns, "input.analysis_type_1=='GSEA'", uiOutput(ns('ui.GSEA_GEX'))),
conditionalPanel(ns = ns, "input.analysis_type_1=='ORA'", uiOutput(ns('ui.ORA_GEX')) ),
DT::dataTableOutput(ns("Expression"))),
tabPanel(title="Gene Set Heatmap", fluidRow( column(4,textInput(ns('analysis_type_2'), 'Analysis Type')%>%disabled()),
column(4,textInput(ns('x2'), 'Gene Set')) ),
actionButton(ns("genesetheatmap"), "Save to output"),
uiOutput(ns("plot.geneset.heatmap"))),
tabPanel(title="KEGG Pathway View",
p("Select a KEGG Pathway by either clicking its name from the results table in the GSEA/ORA tab, or choose/search from the dropdown list below."),
selectizeInput(ns("sel_kegg_set"), label="KEGG Pathway for Visualization", choices = NULL, multiple = FALSE, width="600px",
options = list(placeholder = 'Type to search')),
actionButton(ns("keggSave"), "Save to output"),plotOutput(ns('keggView'))),
tabPanel(title="MetaBase Pathway View",
p("Select a MetaBase Pathway by either clicking its name from the results table in the GSEA/ORA tab, or choose/search from the dropdown list below."),
selectizeInput(ns("sel_metabase_set"), label="MetaBase Pathway for Visualization", choices = NULL, multiple = FALSE, width="600px",
options = list(placeholder = 'Type to search')),
#actionButton(ns("metabaseSave"), "Save to output"),
uiOutput(ns("plot.metabase"))),
tabPanel(title="Wikipathways View",
p("Select a wikipathway by either clicking its name from the results table in the GSEA/ORA tab, or choose/search from the dropdown list below."),
selectizeInput(ns("sel_wikipathways_set"), label="Wikipathways for Visualization", choices = NULL, multiple = FALSE, width="600px",
options = list(placeholder = 'Type to search')),
#actionButton(ns("metabaseSave"), "Save to output"),
svgPanZoomOutput(ns("wikipathways_plot"),width = "100%", height = "800px") ),
tabPanel(title="Help", htmlOutput('help_geneset'))
)
)
)
}
geneset_server <- function(id) {
shiny::moduleServer(id,
function(input, output, session) {
ns <- shiny::NS(id)
#Use metabaser only when the gmt file exists
if (!file.exists("db/human/metabase_maps_genesymbols.gmt")) {
removeTab(session=session, inputId = "geneset_tabset", target = "MetaBase Pathway View")
}
if (!file.exists("db/human/kegg.gmt")) {
removeTab(session=session, inputId = "geneset_tabset", target = "KEGG Pathway View")
}
system="xOmicsShiny"
if (exists("system_info")){
if (!is.null(system_info)) {
if (system_info=="quickomics" ) { system="QuickOmics"}
}
}
#cat(system_info, date(), "\n")
###Modify UI and input data based on QuickOmics or xOmicsShiny system
if (system=="QuickOmics") {
#shinyjs::hide(id = "comparison_2")
working_project=reactiveVal()
observe({
req(ProjectInfo)
working_project(ProjectInfo$ProjectID)
})
#browser()
} else if (system=="xOmicsShiny") {
output$loadedprojects <- renderUI({
req(length(working_project()) > 0)
radioButtons(ns("current_dataset"), label = "Change Working Dataset", choices=DS_names(), inline = F, selected=working_project())
})
output$Second_Comparison<-renderUI({
tagList(
tags$hr(style="border-color: RoyalBlue;"),
checkboxInput(ns("comparison_2"), "Add 2nd Comparison for Gene + Compound Analysis", FALSE, width="95%"),
conditionalPanel(ns = ns, "input.comparison_2==1",
p("Select this option only when you have genes in one comparison, and compounds from the same expriment in another comparison. Compounds should have Gene.Name in KEGG compound ID format(e.g. C12345, C05519).",
style = "color:red; font-size:11px; font-family:arial; font-style:italic"),
selectInput(ns("dataset_2"), label="Dataset", choices=c("None", DS_names()), selected="None"),
selectInput(ns("geneset_test_2nd"), label="Select 2nd Comparison", choices=NULL)
),
tags$hr(style="border-color: RoyalBlue;"),
)
})
observeEvent(input$dataset_2, {
req(input$dataset_2)
if (input$dataset_2!="None"){
DataIn_2 = DataInSets[[input$dataset_2]]
tests_2 = DataIn_2$tests
updateSelectizeInput(session,'geneset_test_2nd',choices=tests_2, selected=tests_2[1])
}
})
observeEvent(input$current_dataset, {
working_project(input$current_dataset)
})
gsea_control<-reactiveVal(0)
ora_control<-reactiveVal(0)
group_order <- reactiveVal()
ProjectInfo<-reactiveValues(ProjectID=NULL, Name=NULL, Species=NULL, ShortName=NULL, file1=NULL, file2=NULL, Path=NULL)
observeEvent(working_project(), {
DataIn=DataInSets[[working_project()]]
ProjectInfo$ProjectID=DataIn$ProjectID
ProjectInfo$Species=DataIn$Species
group_order(DataIn$group_order)
})
DataReactive <-reactive({
req(length(working_project()) > 0)
req(DataInSets[[working_project()]])
Data1<-DataInSets[[working_project()]]
# append 2nd comparison if selected
if (!is.null(input$comparison_2)){
if (input$comparison_2==1) {
if (!is.null(input$dataset_2)) {
if (input$dataset_2!="None" && input$geneset_test_2nd!=""){
Data2<-DataInSets[[input$dataset_2]]
if (!is.null(Data2)){
#browser()
ProteinGeneName1<-Data1$ProteinGeneName%>%dplyr::select(UniqueID, Gene.Name, Protein.ID)
ProteinGeneName2<-Data2$ProteinGeneName%>%dplyr::select(UniqueID, Gene.Name, Protein.ID)
ProteinGeneName_combined<-rbind(ProteinGeneName1, ProteinGeneName2)%>%dplyr::filter(!duplicated(UniqueID))
Data1$ProteinGeneName=ProteinGeneName_combined
#for 2nd comparison, only use new uniqueIDs
results_long1_selTest<-Data1$results_long%>%dplyr::filter(test==input$geneset_test)
results_long2_selTest<-Data2$results_long%>%dplyr::filter(test==input$geneset_test_2nd, !(UniqueID %in% results_long1_selTest$UniqueID) )%>%
mutate(test=input$geneset_test)%>%dplyr::select(UniqueID, Gene.Name, test, logFC, P.Value, Adj.P.Value)
results_long2_otherTests<-Data2$results_long%>%dplyr::select(UniqueID, Gene.Name, test, logFC, P.Value, Adj.P.Value)%>%
dplyr::filter(test!=input$geneset_test_2nd, !(UniqueID %in% ProteinGeneName1$UniqueID),
test %in% unique(Data1$results_long$test) ) #add other tests if test name match
#cat("Add", nrow(results_long2_selTest), "for", input$geneset_test_2nd, " |all other tests", nrow(results_long2_otherTests), "\n") #debug
if (nrow(results_long2_selTest)==0) {results_long2_selTest=NULL}
if (nrow(results_long2_otherTests)==0) {results_long2_otherTests=NULL}
results_long_combined<-rbind(Data1$results_long%>%dplyr::select(UniqueID, Gene.Name, test, logFC, P.Value, Adj.P.Value), results_long2_selTest, results_long2_otherTests)
Data1$results_long=results_long_combined
#combined data_long
data_long1<-Data1$data_long
data_long2<-Data2$data_long%>%dplyr::filter(group %in%data_long1$group, !(UniqueID %in% results_long1_selTest$UniqueID) )
data_long_combined<-rbind(data_long1, data_long2)
Data1$data_long=data_long_combined
}
}
}
}
}
return(Data1)
})
}
###
#active_tests<-reactiveVal(NULL)
observeEvent(working_project(), {
req(working_project())
req(DataReactive())
DataIn = DataReactive()
tests=DataIn$tests
updateSelectizeInput(session,'geneset_test',choices=tests, selected=tests[1])
# active_tests(tests)
#cat("Update tests.", working_project(), tests, "\n")
tests_more=c("None", tests)
updateSelectizeInput(session,'geneset_test2',choices=tests_more, selected="None")
updateSelectizeInput(session,'geneset_test3',choices=tests_more, selected="None")
updateSelectizeInput(session,'geneset_test4',choices=tests_more, selected="None")
updateSelectizeInput(session,'geneset_test5',choices=tests_more, selected="None")
})
observe({
if (!is.null(gmt_file_info)) { #update gmt file choices
gmt_info <- read.csv(gmt_file_info, fileEncoding="UTF-8-BOM")
gmt_use<-gmt_info%>%filter(Show=="YES")%>%mutate(label=str_c(Short_name, " ", label_name, " (", N_sets, ")"))
gmt_choice=gmt_use$gmt_file_name
names(gmt_choice)=gmt_use$label
selH=(gmt_use$Species=="human")
updateCheckboxGroupInput(session, "MSigDB_species_human_GSEA", choices = gmt_choice[selH], selected = gmt_choice[selH][1] )
selM=(gmt_use$Species=="mouse")
updateCheckboxGroupInput(session, "MSigDB_species_mouse_GSEA", choices = gmt_choice[selM], selected = gmt_choice[selM][1])
selR=(gmt_use$Species=="rat")
updateCheckboxGroupInput(session, "MSigDB_species_rat_GSEA", choices = gmt_choice[selR], selected = gmt_choice[selR][1])
}
})
#browser()
observeEvent(working_project(),{
req(ProjectInfo)
if (!is.null(ProjectInfo$Species)) {
prj_species=tolower(str_trim(ProjectInfo$Species))
if (prj_species %in% c("human","mouse", "rat") ) {
updateRadioButtons(session, "MSigDB_species", selected = prj_species)
# cat("Speceis choice updatef, species is", ProjectInfo$Species, "\n")
} else if (prj_species %in% c("cho","chinese hamster", "mus musculus") ) {
updateRadioButtons(session, "MSigDB_species", selected = "mouse")
# cat("Speceis choice updatef, species is", ProjectInfo$Species, "\n")
}
}
})
observeEvent(c(input$MSigDB_species, ProjectInfo$Species), {
req(input$MSigDB_species, ProjectInfo$Species)
if (!is.null(ProjectInfo$Species)) {
species_info=str_c("Current project is for ",ProjectInfo$Species)
if (ProjectInfo$Species!=input$MSigDB_species) {
updateSelectizeInput(session,'map_genes', selected="Homologous Genes")
species_info=str_c(species_info, ", but gene set is from ", input$MSigDB_species, ". Choose how to map to ",
input$MSigDB_species, " genes.")
} else {
updateSelectizeInput(session,'map_genes', selected="No Change (as it is)")
}
output$SpeciesGSEAInfo <- renderText({species_info})
}
#Update MetaBase Pathway View tab
if (file.exists("db/human/metabase_maps_genesymbols.gmt")) {
if (input$MSigDB_species!="human") {
hideTab(session=session, inputId = "geneset_tabset", target = "MetaBase Pathway View")
} else {
showTab(session=session, inputId = "geneset_tabset", target = "MetaBase Pathway View")
}
}
})
observeEvent(input$MSigDB_species, {
kegg_file=str_c("db/", input$MSigDB_species, "/kegg.gmt")
if (file.exists(kegg_file)) {
path1<-gmtPathways(kegg_file)
kegg_names=names(path1)
kegg_choices= c('Type to Search' = '', kegg_names)
#browser()
updateSelectizeInput(session, "sel_kegg_set", choices = kegg_choices, selected="Type to Search", server = TRUE)
}
})
observe({
metabase_file="db/human/metabase_maps_genesymbols.gmt"
if (file.exists(metabase_file)) {
path1<-gmtPathways(metabase_file)
path_names=names(path1)
path_choices= c('Type to Search' = '', path_names)
updateSelectizeInput(session, "sel_metabase_set", choices = path_choices, selected="Type to Search", server = TRUE)
}
})
observeEvent(input$MSigDB_species, {
wiki_file=str_c("db/", input$MSigDB_species, "/Wikipathways_Symbol.gmt")
if (file.exists(wiki_file)) {
path1<-gmtPathways(wiki_file)
wiki_names=names(path1)
wiki_choices= c('Type to Search' = '', wiki_names)
#browser()
updateSelectizeInput(session, "sel_wikipathways_set", choices = wiki_choices, selected="Type to Search", server = TRUE)
}
})
observeEvent(c(input$ORA_input_type, input$geneset_tabset),{
req(input$ORA_input_type, input$geneset_tabset)
if (input$ORA_input_type=='Gene List' && input$geneset_tabset=='Over-Representation Analysis (ORA)') {
hideTab(inputId="geneset_tabset", target="Gene Expression")
hideTab(inputId="geneset_tabset", target="Gene Set Heatmap")
hideTab(inputId="geneset_tabset", target="KEGG Pathway View")
} else if (input$ORA_input_type!='Gene List' || input$geneset_tabset=='Gene Set Enrichment Analysis (GSEA)') {
showTab(inputId="geneset_tabset", target="Gene Expression")
showTab(inputId="geneset_tabset", target="Gene Set Heatmap")
showTab(inputId="geneset_tabset", target="KEGG Pathway View")
}
} )
##################################### GSEA/ORA
DataGenesetReactive_GSEA <- reactive({
DataIn = DataReactive()
results_long = DataIn$results_long
ProteinGeneName = DataIn$ProteinGeneName
comp_sel = input$geneset_test
GSEAgene <- results_long %>% dplyr::filter(test==comp_sel, !is.na(Gene.Name), Gene.Name!="", !is.na(logFC) ) %>%
dplyr::select(one_of(c("Gene.Name","logFC", "P.Value", "Adj.P.Value", "UniqueID", "test"))) %>%
dplyr::distinct(., Gene.Name,.keep_all = TRUE)
#browser()#bebug
GSEA.terminals.df <- GSEAgene %>% arrange(dplyr::desc(logFC))
if (input$map_genes!="No Change (as it is)" && !(ProjectInfo$Species==input$MSigDB_species && input$map_genes=="Homologous Genes") ) {
if ( input$map_genes=="Change to UPPER case (human)" ) mapped_symbols<-toupper(GSEA.terminals.df$Gene.Name)
if ( input$map_genes=="Change to Title Case (mouse/rat)" ) mapped_symbols<-str_to_title(GSEA.terminals.df$Gene.Name)
if (ProjectInfo$Species!=input$MSigDB_species && input$map_genes=="Homologous Genes" ) {
mapped_symbols<-homolog_mapping(GSEA.terminals.df$Gene.Name, ProjectInfo$Species, input$MSigDB_species, homologs) }
GSEA.terminals.df<-GSEA.terminals.df%>%mutate(Gene.Name.Ori=Gene.Name, Gene.Name=mapped_symbols)%>%
dplyr::distinct(., Gene.Name,.keep_all = TRUE)%>%dplyr::filter(!is.na(Gene.Name), Gene.Name!="")
}
if (input$gene_rank_method=="logFC") {
rank_list <- GSEA.terminals.df$logFC
} else { #by -log(P-value)
GSEA.terminals.df <-GSEA.terminals.df %>% mutate(minus_logPvalue=ifelse(logFC<0, log(P.Value), 0-log(P.Value)), minus_logPvalue=round(minus_logPvalue*100)/100 )%>%arrange( dplyr::desc(minus_logPvalue))
rank_list <- GSEA.terminals.df$minus_logPvalue
}
names(rank_list) <- GSEA.terminals.df$Gene.Name
#browser()#bebug
return(list("gene_list" = rank_list, "GSEA.terminals.df" = GSEA.terminals.df ))
}
)
gsets_Reactive <- reactive ({
if (input$MSigDB_species == "human") {
selectedGMT=input$MSigDB_species_human_GSEA
} else if (input$MSigDB_species == "mouse") {
selectedGMT=input$MSigDB_species_mouse_GSEA
} else if (input$MSigDB_species == "rat") {
selectedGMT=input$MSigDB_species_rat_GSEA
}
gsets_GSEA=NULL
for (f in selectedGMT) {
path1<-gmtPathways(str_c("db/", f) ) #read individual GTM file
gsets_GSEA=c(gsets_GSEA, path1)
}
if (input$use_customset) {
if (input$custom_set_option=="Text Box"){
CustomGeneset <- input$CustomGeneset
if(grepl("\n", CustomGeneset)) {
CustomGeneset <- stringr::str_split(CustomGeneset, "\n")[[1]]
} else if (grepl(",", CustomGeneset)) {
CustomGeneset <- stringr::str_split(CustomGeneset, ",")[[1]]
}
CustomGeneset <- gsub(" ", "", CustomGeneset, fixed = TRUE)
CustomGeneset <- unique(CustomGeneset[!is.na(CustomGeneset)])
if (input$MSigDB_species == "human") {CustomGeneset <- toupper(CustomGeneset)}
validate(need(length(CustomGeneset)>2, message = "Please enter at least three custom genes"))
gsets_GSEA=c(gsets_GSEA, list(CustomGeneset=CustomGeneset))
}
if (input$custom_set_option=="File"){
req(input$custom_gmt_file)
CustomGeneset=gmtPathways(input$custom_gmt_file$datapath)
#cat("loaded", length(CustomGeneset), "custom gene sets.\n")
#browser()
gsets_GSEA=c(gsets_GSEA, CustomGeneset)
}
#browser() #debug
}
return(gsets_GSEA)
})
observeEvent(input$compute_gsea, {
gsea_control(gsea_control()+1)
})
gsea_results<- eventReactive (gsea_control(), {
withProgress(message = 'Running GSEA, pleaes be patient...', value = 0, {
getresults <- DataGenesetReactive_GSEA()
gsets_GSEA<-gsets_Reactive()
validate(need(length(gsets_GSEA)>0,"Please select at least one gene set."))
#browser()#bebug
logFC_list <- getresults$gene_list
############################
gsMin = input$gsetMin
gsMax = input$gsetMax
############################
output <- fgseaMultilevel(gsets_GSEA,logFC_list,minSize=gsMin,maxSize=gsMax)
if (input$gsea_collapase) {
collapsed_set <- collapsePathways(output[order(pval)][padj <= input$gsea_FDR], gsets_GSEA,logFC_list )
output= output[pathway %in% collapsed_set$mainPathways]
}
res = output %>% # Using dplyr functions
mutate_if(is.numeric,
signif,
digits = 3) #some may fail for very small numbers (<1e-20), added formatSignif in datatable as well.
res <- res %>% dplyr::rename(GeneSet=pathway)%>%
dplyr::select(-ES, -log2err) %>% #keep leadingEdge
arrange(padj, dplyr::desc(abs(NES))) %>%dplyr::filter(padj<=input$gsea_FDR)%>%
rownames_to_column('rank') %>%
relocate(GeneSet)
} )
return(res)
} )
output$MSigDB_GSEA <- DT::renderDT(server=FALSE,{ withProgress(message = 'Processing...', value = 0, {
res<-gsea_results()
validate(need(nrow(res)>0,"No results. Try to increase p.adj cutoff, or try a different comparison."))
res$Action<-vapply(1:nrow(res), function(i){
as.character(
rclipButton(
paste0("clipbtn_", i),
label = "Copy Leading Edge Genes",
clipText = paste(unlist(res[i, "leadingEdge"]), collapse=","),
#icon = icon("clipboard"),
icon = icon("copy", lib = "glyphicon"),
class = "btn-primary btn-sm"
)
)
}, character(1L))
res<-res%>%dplyr::relocate(Action, .before=leadingEdge)
DT::datatable(
res, extensions = 'Buttons', escape = FALSE, selection = 'none', class = 'cell-border strip hover',
options = list( dom = 'lBfrtip', pageLength = 15,
buttons = list(
list(extend = "csv", text = "Download Page", filename = "Page_results",
exportOptions = list(modifier = list(page = "current"))),
list(extend = "csv", text = "Download All", filename = "All_Results",
exportOptions = list(modifier = list(page = "all")))
)
) )%>%formatSignif(columns=c('pval', "padj"), digits=3) %>% formatStyle(1, cursor = 'pointer',color='blue')
})
})
observeEvent(input$MSigDB_GSEA_cell_clicked, {
info = input$MSigDB_GSEA_cell_clicked
if (is.null(info$value) || info$col != 1) return()
analysis_type = 'GSEA'
updateTabsetPanel(session, 'geneset_tabset', selected = 'Gene Expression')
updateTextInput(session, 'x1', value = info$value)
updateTextInput(session, 'x2', value = info$value)
#updateTextInput(session, 'x3', value = info$value)
updateSelectizeInput(session, "sel_kegg_set",selected=info$value)
updateSelectizeInput(session, "sel_metabase_set",selected=info$value)
updateSelectizeInput(session, "sel_wikipathways_set",selected=info$value)
updateTextInput(session, 'analysis_type_1', value = analysis_type)
updateTextInput(session, 'analysis_type_2', value = analysis_type)
# updateTextInput(session, 'analysis_type_3', value = analysis_type)
})
####################### ORA
DataGenesetReactive_ORA <- reactive({
req(DataReactive(), input$ORA_input_type, input$map_genes)
req( input$geneset_test %in% DataReactive()$tests)
if (input$ORA_input_type!='Gene List') {
DataIn = DataReactive()
results_long = DataIn$results_long
#ProteinGeneName = DataIn$ProteinGeneName
comp_sel = input$geneset_test
all_genes <-results_long %>% dplyr::filter(test == comp_sel) %>%dplyr::filter(!is.na(Gene.Name), Gene.Name!="")%>%
dplyr::select(one_of(c("Gene.Name"))) %>%
collect %>% .[["Gene.Name"]] %>% unique()
absFCcut = log2(as.numeric(input$geneset_FCcut))
pvalcut = as.numeric(input$geneset_pvalcut)
terminals.df <- results_long %>% dplyr::filter(test == comp_sel) %>%dplyr::filter(!is.na(Gene.Name), Gene.Name!="")%>%
dplyr::select(one_of(c("Gene.Name","logFC","P.Value", "Adj.P.Value", "UniqueID", "test")))%>%arrange(P.Value) %>%
dplyr::distinct(., Gene.Name,.keep_all = TRUE)
#browser()#bebug
#terminals.df <- filteredgene%>%arrange(P.Value) #old way
if (input$map_genes!="No Change (as it is)" && !(ProjectInfo$Species==input$MSigDB_species && input$map_genes=="Homologous Genes") ) {
if (input$map_genes=="Change to UPPER case (human)") {
mapped_symbols<-toupper(terminals.df$Gene.Name); all_genes=toupper(all_genes)
} else if ( input$map_genes=="Change to Title Case (mouse/rat)" ) {
mapped_symbols<-str_to_title(terminals.df$Gene.Name); all_genes=str_to_title(all_genes)
} else if (ProjectInfo$Species!=input$MSigDB_species && input$map_genes=="Homologous Genes" ) {
mapped_symbols<-homolog_mapping(terminals.df$Gene.Name, ProjectInfo$Species, input$MSigDB_species, homologs)
all_genes <-homolog_mapping(all_genes , ProjectInfo$Species, input$MSigDB_species, homologs)
}
terminals.df<-terminals.df%>%mutate(Gene.Name.Ori=Gene.Name, Gene.Name=mapped_symbols)%>%
dplyr::distinct(., Gene.Name,.keep_all = TRUE)%>%dplyr::filter(!is.na(Gene.Name), Gene.Name!="")
}
filteredgene <- terminals.df %>% mutate(psel=input$geneset_psel, P.stat=ifelse(psel == "Padj", Adj.P.Value, P.Value)) %>%
dplyr::filter(abs(logFC) > absFCcut, P.stat < pvalcut) %>%
dplyr::select(one_of(c("Gene.Name","logFC","P.Value", "Adj.P.Value", "UniqueID", "test")))
sig_genes <- filteredgene$logFC
names(sig_genes) <- filteredgene$Gene.Name
sig_genes_Dir=sig_genes
if (input$geneset_direction=="Up") {
sig_genes_Dir=sig_genes[sig_genes>0]
} else if (input$geneset_direction=="Down") {
sig_genes_Dir=sig_genes[sig_genes<0]
}
#output$geneset_filteredgene <- renderText({ paste("Selected Genes:",length(sig_genes_Dir), " (",input$geneset_direction, " Direction)", sep="")})
return(list("sig_genes" = sig_genes, "all_genes" = all_genes, "terminals.df"=terminals.df, "sig_genes_Dir" = sig_genes_Dir))
}
})
DataGenesetReactive_ORA_list <- reactive({
if (input$ORA_input_type=='Gene List') {
ORA_list <- input$ORA_list
ORA_list=str_replace_all(ORA_list, " ", "")
if(grepl("\n",ORA_list)) {
ORA_list <- stringr::str_split(ORA_list, "\n")[[1]]
} else if(grepl(",",ORA_list)) {
ORA_list <- stringr::str_split(ORA_list, ",")[[1]]
}
ORA_list<-ORA_list [ORA_list !=""]
validate(need(length(ORA_list)>1, message = "Please input at least 2 valid genes."))
DataIn = DataReactive()
ProteinGeneName = DataIn$ProteinGeneName
all_genes <- dplyr::filter(ProteinGeneName, !is.na(Gene.Name), Gene.Name!="") %>%
dplyr::select(one_of(c("Gene.Name"))) %>% collect %>% .[["Gene.Name"]] %>% unique()
if (input$map_genes!="No Change (as it is)" && !(ProjectInfo$Species==input$MSigDB_species && input$map_genes=="Homologous Genes") ) {
if (input$map_genes=="Change to UPPER case (human)") {
ORA_list<-toupper(ORA_list); all_genes=toupper(all_genes)
} else if ( input$map_genes=="Change to Title Case (mouse/rat)" ) {
ORA_list<-str_to_title(ORA_list); all_genes=str_to_title(all_genes)
} else if (ProjectInfo$Species!=input$MSigDB_species && input$map_genes=="Homologous Genes" ) {
ORA_list<-homolog_mapping(ORA_list, ProjectInfo$Species, input$MSigDB_species, homologs)
all_genes <-homolog_mapping(all_genes , ProjectInfo$Species, input$MSigDB_species, homologs)
}
}
if (input$ORA_universe!="Genes in current project") {
gsets_GSEA<-gsets_Reactive()
all_genes<-unlist(gsets_GSEA)%>%unique()
}
sig_genes=rep(1, length(ORA_list))
names(sig_genes)=ORA_list
return(list("sig_genes" = sig_genes, "all_genes" = all_genes, "terminals.df"=NULL, "sig_genes_Dir" = NULL))
}
})
observe({
req(working_project())
req(input$geneset_test)
req(DataReactive())
req(DataGenesetReactive_ORA())
req(DataGenesetReactive_ORA()$sig_genes)
tmpdat=DataGenesetReactive_ORA()$sig_genes
output$filteredgene1 <- renderText({paste("Genes Pass Cutoff (DEGs):",length(tmpdat),sep="")})
output$filteredgene2 <- renderText({paste("Genes Up: ", sum(tmpdat>0), "; Genes Down: ", sum(tmpdat<0),sep="")})
DEGs=names(tmpdat)
updateTextAreaInput(session, "ORA_list", value=paste(DEGs, collapse="\n"))
})
observeEvent(input$compute_ora, {
ora_control(ora_control()+1)
})
ora_results<- eventReactive (ora_control(), {
withProgress(message = 'Running ORA...', value = 0, {
gsets_GSEA<-gsets_Reactive()
validate(need(length(gsets_GSEA)>0,"Please select at least one gene set."))
getresults <- DataGenesetReactive_ORA()
logFC_list <- getresults$sig_genes
all_genes <- getresults$all_genes
gsa <- ORAEnrichment (deGenes=names(logFC_list),universe=all_genes, gsets_GSEA, logFC =logFC_list, Dir=input$geneset_direction)
if (input$ora_collapase) {
Dir=input$geneset_direction
logFC_list1=logFC_list
if (Dir=="Up") {logFC_list1=logFC_list[logFC_list>0]
} else if (Dir=="Down") {logFC_list1=logFC_list[logFC_list<0]}
collapsed_set <- collapsePathwaysORA(foraRes=gsa%>%mutate(pathway=GeneSet)%>%filter(p.adj<= input$ora_pvalue),
pathways=gsets_GSEA,genes=names(logFC_list1), universe=all_genes, pval.threshold=0.05)
#browser()
gsa<-gsa%>%dplyr::filter(GeneSet %in% collapsed_set$mainPathways)
}
############################
#browser()
res <- gsa %>%dplyr::filter( p.adj <= input$ora_pvalue) # Using dplyr functions
# mutate_if(is.numeric,signif,digits = 3)
})
})
ora_results_list<- eventReactive (ora_control(), {
withProgress(message = 'Running ORA...', value = 0, {
gsets_GSEA<-gsets_Reactive()
validate(need(length(gsets_GSEA)>0,"Please select at least one gene set."))
getresults <- DataGenesetReactive_ORA_list()
logFC_list <- getresults$sig_genes
all_genes <- getresults$all_genes
gsa <- ORAEnrichment (deGenes=names(logFC_list),universe=all_genes, gsets_GSEA, logFC =logFC_list, Dir="Both")%>%
dplyr::select(-DE_UpGene, -DE_DownGene, -DE_Direction)
if (input$ora_collapase) {
collapsed_set <- collapsePathwaysORA(foraRes=gsa%>%mutate(pathway=GeneSet)%>%filter(p.adj<= input$ora_pvalue),
pathways=gsets_GSEA,genes=names(logFC_list), universe=all_genes, pval.threshold=0.05)
gsa<-gsa%>%dplyr::filter(GeneSet %in% collapsed_set$mainPathways)
}
############################
res <- gsa %>%dplyr::filter( p.adj <= input$ora_pvalue) # Using dplyr functions
#mutate_if(is.numeric,signif,digits = 3)
})
})
output$MSigDB_ORA <-DT::renderDT(server=FALSE,{ withProgress(message = 'Processing...', value = 0, {
res<-ora_results()
validate(need(nrow(res)>0,"No results. Try to increase p.adj cutoff, or ajust DEG cutoff."))
res$Action<-vapply(1:nrow(res), function(i){
as.character(
rclipButton(
paste0("clipbtn_", i),
label = "Copy DE Gene Names",
clipText = res[i, "DeGene_in_Set"],
#icon = icon("clipboard"),
icon = icon("copy", lib = "glyphicon"),
class = "btn-primary btn-sm"
)
)
}, character(1L))
res<-res%>%dplyr::relocate(Action, .before=DeGene_in_Set)
DT::datatable(
res, extensions = 'Buttons', escape = FALSE, selection = 'none', class = 'cell-border strip hover',
options = list( dom = 'lBfrtip', pageLength = 15,
buttons = list(
list(extend = "csv", text = "Download Page", filename = "Page_results",
exportOptions = list(modifier = list(page = "current"))),
list(extend = "csv", text = "Download All", filename = "All_Results",
exportOptions = list(modifier = list(page = "all")))
)) )%>%formatSignif(columns=c('p.value', "p.adj"), digits=3) %>% formatStyle(1, cursor = 'pointer',color='blue')
}) })
output$MSigDB_ORA_list <-DT::renderDT(server=FALSE,{ withProgress(message = 'Processing...', value = 0, {
res<-ora_results_list()
validate(need(nrow(res)>0,"No results. Try to increase p.adj cutoff, or use a different list."))
res$Action<-vapply(1:nrow(res), function(i){
as.character(
rclipButton(
paste0("clipbtn_", i),
label = "Copy DE Gene Names",
clipText = res[i, "DeGene_in_Set"],
#icon = icon("clipboard"),
icon = icon("copy", lib = "glyphicon"),
class = "btn-primary btn-sm"
)
)
}, character(1L))
res<-res%>%dplyr::relocate(Action, .before=DeGene_in_Set)
DT::datatable(
res, extensions = 'Buttons', escape = FALSE,
options = list( dom = 'lBfrtip', pageLength = 15,
buttons = list(
list(extend = "csv", text = "Download Page", filename = "Page_results",
exportOptions = list(modifier = list(page = "current"))),
list(extend = "csv", text = "Download All", filename = "All_Results",
exportOptions = list(modifier = list(page = "all")))
)) )%>%formatSignif(columns=c('p.value', "p.adj"), digits=3)
}) })
observeEvent(input$MSigDB_ORA_cell_clicked, {
if (input$ORA_input_type!='Gene List') {
info = input$MSigDB_ORA_cell_clicked
if (is.null(info$value) || info$col != 1) return()
analysis_type = 'ORA'
updateTabsetPanel(session, 'geneset_tabset', selected = 'Gene Expression')
updateTextInput(session, 'x1', value = info$value)
updateTextInput(session, 'x2', value = info$value)
#updateTextInput(session, 'x3', value = info$value)
updateSelectizeInput(session, "sel_kegg_set",selected=info$value)
updateSelectizeInput(session, "sel_metabase_set",selected=info$value)
updateSelectizeInput(session, "sel_wikipathways_set",selected=info$value)
updateTextInput(session, 'analysis_type_1', value = analysis_type)
updateTextInput(session, 'analysis_type_2', value = analysis_type)
#updateTextInput(session, 'analysis_type_3', value = analysis_type)
}
})
output$ui.ORA_GEX <- renderUI({
tagList(
DT::dataTableOutput(ns('selected_ORA_set')),
h5("The table below contains all genes from the selected gene set. Selected DE genes for ORA are shown in green."))
})
output$ui.GSEA_GEX <- renderUI({
tagList(
DT::dataTableOutput(ns('selected_GSEA_set')),
h5("GSEA Plot"),
plotOutput(ns('GSEA_plot')),
textOutput(ns("leadingEdge_genes")),
h5("The table below contains all genes from the selected gene set. Leading edge genes are shown in green."))
})
sel_GSEA_set<- reactive({
analysis_type = input$analysis_type_1
if (analysis_type=="GSEA"){
res<-gsea_results()
ID = input$x1
if (ID!=""){
sel_res<-res%>%filter(GeneSet==ID)
sel_resT<-sel_res%>%dplyr::select(-leadingEdge)
LE_Genes=sel_res$leadingEdge[[1]]
return(list(table=sel_resT, genes=LE_Genes))
} else {return(list(table=NULL, genes=NULL)) }
} else {return(list(table=NULL, genes=NULL)) }
})
output$selected_GSEA_set <- DT::renderDT(server=FALSE, {
validate(need(sel_GSEA_set()$table, "select a gene set from GSEA table"))
DT::datatable(sel_GSEA_set()$table, rownames=F, options = list(dom="t", ordering=F))%>%formatSignif(columns=c('pval', "padj"), digits=3)
} )
output$leadingEdge_genes <- renderText({
genes=sel_GSEA_set()$genes
paste("Leading Edge Genes (the core group of genes that accounts for the gene set's enrichment signal):", paste(genes, collapse = ", "))
})
output$GSEA_plot = renderPlot({
getresults <- DataGenesetReactive_GSEA()
gsets_GSEA<-gsets_Reactive()
ID = input$x1
logFC_list <- getresults$gene_list
plotEnrichment(gsets_GSEA[[ID]],logFC_list) + labs(title=ID)
}, height=400)
sel_ORA_set<- reactive({
analysis_type = input$analysis_type_1
if (analysis_type=="ORA"){
res<-ora_results()
ID = input$x1
if (ID!=""){
sel_res<-res%>%filter(GeneSet==ID)
#cat("ORA selected", ID, "\n")
return(list(table=sel_res))
} else {return(list(table=NULL)) }
} else {return(list(table=NULL)) }
})
output$selected_ORA_set <- DT::renderDT(server=FALSE, {
validate(need(sel_ORA_set()$table, "select a gene set from ORA table"))
DT::datatable(sel_ORA_set()$table, rownames=F, options = list(dom="t", ordering=F))%>%formatSignif(columns=c('p.value', "p.adj"), digits=3)
} )
keggView_out <- reactive({withProgress(message = 'Making KEGG Pathway View...', value = 0, {
#analysis_type = input$analysis_type_2
#ID = input$x3
ID=input$sel_kegg_set
validate(need(ID!="", message = "Please select a KEGG pathway to map logFC data to it."))
validate(need(str_detect(ID, "^(hsa|mmu|rno)\\d{5}"), message = "Only works on human/mouse/rat KEGG pathways."))
species=input$MSigDB_species
if (species=="rat") {species="rno"}
pid <- strsplit(ID,"_")[[1]][1]
img.file <- paste(pid,"pathview","png",sep=".")
dataIn=DataReactive()
results_long=dataIn$results_long
ProteinGeneName = dataIn$ProteinGeneName
comp_sel = input$geneset_test
data_results=dataIn$data_results
if (file.exists(img.file)) {
file.remove(img.file)
}
#get logFC data from data_results
tests=input$geneset_test
if (input$kegg_more_tests=="Yes") {
if (input$geneset_test2!="None") {tests=c(tests, input$geneset_test2)}
if (input$geneset_test3!="None") {tests=c(tests, input$geneset_test3)}
if (input$geneset_test4!="None") {tests=c(tests, input$geneset_test4)}
if (input$geneset_test5!="None") {tests=c(tests, input$geneset_test5)}
}
##Make FCdata from results_long
res1<-results_long%>%dplyr::filter(test==comp_sel)%>%dplyr::select(UniqueID, logFC); names(res1)[2]=comp_sel
FC_df<-data.frame(UniqueID=unique(results_long$UniqueID))%>%left_join(ProteinGeneName%>%dplyr::select(UniqueID, Gene.Name))%>%
left_join(res1)
if (length(tests)>1) {
for (i in 2:length(tests)){
comp_add=tests[i]
res1<-results_long%>%dplyr::filter(test==comp_add)%>%dplyr::select(UniqueID, logFC); names(res1)[2]=comp_add
FC_df<-FC_df%>%left_join(res1)
}
}
if (input$map_genes!="No Change (as it is)" && !(ProjectInfo$Species==input$MSigDB_species && input$map_genes=="Homologous Genes") ) {
if ( input$map_genes=="Change to UPPER case (human)" ) mapped_symbols<-toupper(FC_df$Gene.Name)
if ( input$map_genes=="Change to Title Case (mouse/rat)" ) mapped_symbols<-str_to_title(FC_df$Gene.Name)
if (ProjectInfo$Species!=input$MSigDB_species && input$map_genes=="Homologous Genes" ) {
mapped_symbols<-homolog_mapping(FC_df$Gene.Name, ProjectInfo$Species, input$MSigDB_species, homologs) }
FC_df<-FC_df%>%mutate(Gene.Name.Ori=Gene.Name, Gene.Name=mapped_symbols)
}
selCol=which(names(FC_df) %in% tests)
sel_gene=which(!is.na(FC_df$Gene.Name))
FCdata=data.matrix(FC_df[sel_gene, selCol])
all.names=FC_df$Gene.Name[sel_gene]
rownames(FCdata)=all.names
if (ncol(FCdata)>1) { img.file <- paste(pid,"pathview.multi.png",sep=".")}
#Separte genes and compounds
is.compound=str_detect(all.names, "C\\d{5}$")
FCdata_gene=FCdata[!is.compound, , drop=F]
FCdata_compound=FCdata[is.compound, , drop=F]
#browser()
if (sum(!is.compound)>0) {
tmp <- try (pathview(gene.data=FCdata_gene, cpd.data=FCdata_compound, pathway.id=pid, kegg.dir="./kegg", kegg.native = T, gene.idtype="SYMBOL", species=species,
low = list(gene = "green", cpd = "blue"), mid = list(gene = "gray90", cpd = "gray90"), high = list(gene = "red", cpd ="yellow"),
same.layer = F, map.symbol=as.logical(input$kegg_mapsample), limit=list(gene=as.numeric(input$kegg_logFC), cpd=as.numeric(input$kegg_logFC_cpd)) ) )
if (class(tmp) == "try-error") { #if no gene mapped, the above command will fail, try the one below with compound only
tmp <- pathview(cpd.data=FCdata_compound, pathway.id=pid, kegg.dir="./kegg", kegg.native = T, species=species,
low = list(gene = "green", cpd = "blue"), mid = list(gene = "gray90", cpd = "gray90"), high = list(gene = "red", cpd ="yellow"),
same.layer = F, limit=list(gene=as.numeric(input$kegg_logFC), cpd=as.numeric(input$kegg_logFC_cpd)) )
}
} else {
tmp <- pathview(cpd.data=FCdata_compound, pathway.id=pid, kegg.dir="./kegg", kegg.native = T, species=species,
low = list(gene = "green", cpd = "blue"), mid = list(gene = "gray90", cpd = "gray90"), high = list(gene = "red", cpd ="yellow"),
same.layer = F, limit=list(gene=as.numeric(input$kegg_logFC), cpd=as.numeric(input$kegg_logFC_cpd)) )
}
#browser() #debug
return(img.file)
})
})
output$wikipathways_plot <- renderSvgPanZoom({withProgress(message = 'Making WikiPathways View...', value = 0, {
ID=input$sel_wikipathways_set