R/enrichMir.app.ui.R

In ETHZ-INS/enrichMiR: enrichMiR: miRNA target enrichment analysis

#' @import shiny shinydashboard shinycssloaders
#' @importFrom plotly plotlyOutput
#' @importFrom shinycssloaders withSpinner
#' @importFrom shinyjs useShinyjs runjs
#' @importFrom shinyjqui jqui_resizable
#' @importFrom rintrojs introjsUI
#' @importFrom waiter use_waiter waiter_show_on_load waiter_hide spin_1
#' @importFrom DT DTOutput
#' @export
enrichMiR.ui <- function(){

  genes_placeholder <- paste("Enter your genes as symbols or ensembl IDs,",
                             "separated by spaces, commas, linebreaks or directly paste a spreadsheet column. E.g.:
EZH2, YY1, SHANK3, ...\nor:
ENSG00000106462, ENSG00000100811, ...")
  ggplot_themes <- c(gsub("^theme_","",setdiff(grep("^theme_",ls(getNamespace("ggplot2"),
                                             all.names=TRUE),value=TRUE),
                           paste0("theme_",c("all_null","set","update","gray",
                                             "get","replace","void")))),
                     "classic2", "pubr", "pubclean")

  ui <- dashboardPage(
    dashboardHeader(title="enrichMiR", titleWidth="300px",
      dropdownMenu(icon=tagList(icon("question"),tags$span(" Help")),
        headerText="Documentation topics:", type="notifications", badgeStatus=NULL,
        tags$li(tags$a("Interactive tour", id="helpBtn", href="#",
                       class="action-button shiny-bound-input")),
        tags$li(tags$a("Overview", id="overview", href="#",
                       class="action-button shiny-bound-input")),
        tags$li(tags$a("Binding sites collections", id="help_collections2", href="#",
                       class="action-button shiny-bound-input")),
        tags$li(tags$a("Enrichment tests", id="help_tests2", href="#",
                       class="action-button shiny-bound-input")),
        tags$li(tags$a("CD plots", id="help_cdplot2", href="#",
                       class="action-button shiny-bound-input")),
        tags$li(tags$a("Browser compatibility", id="brow_comp", href="#",
                       class="action-button shiny-bound-input"))
        )
    ),
    ## Sidebar content
    dashboardSidebar(width = "300px",
       sidebarMenu(id="main_tabs",
         menuItem("Introduction", tabName = "tab_intro", icon=icon("info")),
         tags$hr(width="80%"),
         menuItemOutput("menu_species"),
         menuItemOutput("menu_input"),
         menuItemOutput("menu_enrich"),
         menuItemOutput("menu_cdplot"),
         tags$hr(width="80%"),
         menuItem("Tests & benchmark", tabName="tab_benchmark",
                  icon=icon("tachometer-alt"))
       )
    ),

    ## Body Content
    dashboardBody(
      useShinyjs(), introjsUI(), use_waiter(),

      waiter_show_on_load(html=tagList(
        #tags$h1("enrichMiR"),
        tags$img(src="enrichMiR_sticker.png"),
        tags$h3("Please wait while the application is initialized..."),
        spin_1()
      )),
      tabItems(
        tabItem(tabName = "tab_intro",
          box(title="enrichMiR: miRNA target enrichment analysis", width=12,
              tags$img(src="enrichMiR_sticker.png", style="float: right;"),
              tags$p(
                "This app will allow you to identify miRNAs whose targets are ",
                "enriched among genesets of interest or a differential ",
                "expression signature, and produce related visualizations.",
                "Although the app was chiefly developed (and benchmarked) for ",
                "miRNAs, some support is also offered to run the same analyses",
                " using RNA-binding proteins."),
              tags$ol("The app has two main functionalities:",
                tags$li("performing ", tags$b("target enrichment analysis"),
                        ", either comparing your gene set of interest to a
                        background set, or using the results of a differential
                        expression analysis (DEA)."),
                tags$li("generating foldchange cumulative distribution (CD)
                        plots comparing targets and non-targets (requires the
                        results of a differential expression analysis as input).")
              ), tags$br(),
              tags$p("To get started, take a ",
                     actionLink("helpLink", "quick tour"),
                     " of the app, or browse the help on the upper-right corner."),
              tags$p("Please report any bug in the ",
                     tags$a(href="https://github.com/ETHZ-INS/enrichMiR",
                            "github repository"),
                     "."),
              tags$br(),
              tags$p( style="text-align: right;",
                      paste("enrichMiR version",packageVersion("enrichMiR")),
                      "; ", tags$a( href="http://schrattlab.ethz.ch",
                                    "Schratt lab", target="_blank") )
          )
        ),

        tabItem(tabName = "tab_species", ############ SPECIES / COLLECTION
          box(title="Select Species and Collection", width=12,
            column(7, selectInput(inputId = "species", "Species", width='98%',
                        choices = c("Human", "Mouse", "Rat", "Fish","Fly","Worm")), tags$br(),
               tags$div(id="collection_input",
                  actionButton(inputId="help_collections", style="float:right;",
                           icon=icon("question-circle"), label=""),
                  selectInput(inputId="collection", width='98%', choices=c(),
                    label="Select a binding sites collection",
                    selected="Targetscan conserved miRNA BS")
                  )),
            column(5, tags$p("Note that some collections (e.g. scanMiR) might
                             take a moment to load."),
                   withSpinner(textOutput("collection_details")))
          ),
          tags$div(id="exprMirs_box",
                   box(title="Specify expressed miRNAs (optional)",
                       collapsible=TRUE, collapsed=TRUE, width=12,
            tags$p("miRNA expression can be used to restrict and annotate the ",
                   "enrichment analysis. This information can either be given ",
                   "manually, provided by uploading a miRNA profile, or ",
                   "fetched from pre-loaded miRNA expression profiles"),
            tags$div(id="expressed_mirna_outer",
            tabBox(id="expressed_mirna_box", width=12,
              tabPanel(title = "Custom Set",
                       "Paste a list of expressed miRNAs in 'miRBase' format", br(), br(),
                        textAreaInput(inputId = "exp_mirna_list",
                            label="miRNA List",
                            rows=5,
                            placeholder="Enter miRbase IDs, separated by spaces, commas, or linebreaks. E.g.:
  hsa-miR-30b-5p
  hsa-miR-30d-5p
  ...",
                            resize="vertical")),
              tabPanel(title = "Upload miRNA expression table",
                fileInput(inputId="exp_mirna_file",
                          label="Upload miRNA expression object as '*.csv' file (see below for format)",
                          accept=c("text/csv", ".csv",".tab",".txt",
                                   "text/comma-separated-values,text/plain")),
                div(style = "margin-top: -30px"),
                tags$p("miRNA expression tables should have the following format: miRBase name in the first
                            column, expression-values in the second column"),br(), br(),
                sliderInput(inputId="mir_cut_off",
                            label="Select miRNA expression cut-off:",
                            min=10, max=100, post=" %", value=50),
                "Keep only the top ..% expressed miRNAs"
              ),
              tabPanel(title="Use preset expression profile",
                withSpinner(uiOutput("mirexp_preset")),
                sliderInput(inputId="mir_cut_off2",
                            label="Select miRNA expression cut-off:",
                            min=10, max=100, post=" %", value=50 ),
                "Keep only the top ..% expressed miRNAs"
              )
            )), br(),
            footer="Note: If no miRNAs are uploaded/selected, enrichment
                    searches will be performed with all miRNAs of the given species"))
        ),


        tabItem("tab_input", ############ INPUT
          tags$h4("Choose between the two following input options"),
          tags$p("You may either upload the results of a differential expression
                 analysis (DEA), or provide a set of genes of interest against
                 a background set."),
          tabBox(id="input_type", width=12,
            tabPanel(title = "Upload DEA results", value = "dea",
              fluidRow(
                column(7, fileInput( inputId = "dea_input",
                  label="Upload DEA object as '*.csv' file (see help)",
                  accept=c("text/csv", ".csv", ".tab", ".txt",
                           "text/comma-separated-values,text/plain")),
                       "Or: ", actionButton("example_dea", "Use example DEA"),
                  tags$hr(), tags$br(),
                  tags$p("Upload a Differential Expression Analysis (DEA) as
                a table with at least following information: Ensembl ID or Gene
                Symbol as identifier in the first column, as well as
                logFC-values and FDR-values."),
                  tags$p("Note that we recommend filtering the DEA to retain
                only the most highly expressed genes (e.g. top 5000).")),
                column(2, actionButton(inputId="help_deaformat",
                          icon=icon("question-circle"), label="View format")),
                column(3, withSpinner(htmlOutput("dea_res")), tags$br(),
                       tags$hr(), tags$br(),
                     sliderInput(inputId = "dea_sig_th",
                                 label="Select significance threshold",
                                 min=0.01, max=0.5, value=0.05, step=0.01))
              )
            ),
            tabPanel(title = "Select geneset & background",
              tags$p("In this mode, your genes of interest are compared against
                     a background of genes."),
              tags$h3("Genes of interest"),
              tabsetPanel(id="GOI",
                tabPanel(title = "Custom set", value = "GOI_custom",
                         "Paste a list of expressed genes as shown in the window below. A minimum number of two genes is required.",
                         br(), br(),
                         textAreaInput(inputId = "genes_of_interest",
                                       label="Gene List", rows=5, width="100%",
                                       value=NULL, resize="vertical",
                                       placeholder=genes_placeholder),
                ),
                tabPanel(title = "From Gene Ontology", value="GOI_GO",
                         radioButtons(inputId = "genes_format", label = "Select:",
                                      choices = c("Ensembl" = "Ens",
                                                  "Gene Symbol" = "GS"),
                                      selected = "Ens"),
                         selectizeInput(inputId="go_term", "Select GO-Term", choices=c()),
                         textOutput("GOI_nb"))
              ),
              br(), tags$hr(), tags$h3("Background (required)"),
              actionButton(inputId="help_background", style="float:right;",
                           icon=icon("question-circle"), label="Help on background"),
              textAreaInput(inputId = "background_genes",
                            label="Gene List",
                            rows=5, width="100%",
                            value=NULL,
                            placeholder=paste(genes_placeholder,"
Note that the background should also include the genes of interest!"),
                            resize="vertical"),br(),
              actionButton("example_GOI", "Example genes"),
              footer=paste("Note: If you want to use the Targetscan miRNA annotations",
                           " together with rat genes, use the 'Gene Symbol' format")
            ),
          )
        ),


        tabItem(tabName = "tab_enrich", ###### ENRICHMENT ANALYSIS
          column(3, tags$div(id="enrichbtn_outer",
                             withSpinner(uiOutput("enrichbtn")))),
          box(width=9, title="Advanced enrichment options", collapsible=TRUE,
              collapsed=TRUE, sliderInput(inputId="minsize",
                label="Minium number of annotated targets that is required to
                       consider the miRNA-family for testing",
                          min=1, max=20, value=5, step=1),
              br(),
              box(width="100%", title = "Advanced Options", collapsible=TRUE, collapsed=TRUE,
                  actionButton(inputId="help_testsadvanced", style="float:right;",
                               icon=icon("question-circle"), label=""),
                  tags$h5(em(
                    "We recommend to only change test settings after reading the",
                    " enrichMiR documentation and the benchmark.")),
                  tags$h5(em("Some tests are always performed by default, namely
                    the 'siteoverlap' test and (except for some annotations and
                    assuming a DEA input) the 'areamir' test.")),
                  uiOutput("extratestinput")
              )
            ),
          uiOutput("enrich_possible"),
          tags$div(id="resultsbox", style="display: none; height: 100%;",
          box(width=12, title="Results", collapsible=TRUE,
            fluidRow(
              column(7, id="sel_test_div",
                     selectInput("view_test", "Select test to visualize",
                                 choices=c())),
              column(1, style="margin-top: 25px;",
                     actionButton(inputId="help_tests",
                                  icon=icon("question-circle"), label="")),
            ),
            tabBox(id="enrichresults_out", width=12,
              tabPanel(title="Enrichment plot",
                fluidRow(
                  column(11, tags$p("Hover on a point to view family members ",
                                    " and enrichment-related statistics.")),
                  column(1, actionButton(inputId="help_enrichplot",
                                      icon=icon("question-circle"), label=""))),
                withSpinner(plotlyOutput("bubble_plot")),
                tags$br(), htmlOutput("hoverinfo"), tags$br(),
                box(title="Plot options", width=12, collapsible=TRUE, collapsed=TRUE,
            column(6,sliderInput(inputId="label.sig.thres",
                                 "Significance threshold to display labels",
                                 min=0, max=0.25, value=0.05, step=0.01)),
            column(6,sliderInput(inputId="label.enr.thres",
                                 "Enrichment threshold to display labels",
                                 min=0.5, max=10, value=1, step=0.5)),
            column(6, numericInput(inputId="label_n", value=10, min=1, max=50,
                                   label="Max number of Labels")),
            column(6, radioButtons(inputId="sig.field",
                                   label="Display on y-axis:",
                                   choices=c("pvalue","FDR"), selected="FDR")),
            column(6, selectInput("bubble_theme", "Theme",
                                  choices=ggplot_themes)),
            column(6, downloadButton('bubble_plot_dl', label="Download plot"),
                      actionButton(inputId="help_enrichplotFurther",
                                   label="Further customization?"))
                )),
              tabPanel(title="Results table",
                fluidRow(
                 column(8, checkboxGroupInput(
                   inputId="columns2show", selected=NULL, inline=TRUE,
                   label="Select add. columns to be shown:",
                   choices=list("miRNA names"="members",
                                "predicted target genes"="genes") )),
                 column(4, downloadButton('dl_hits', label = "Download all"),
                        downloadButton('dl_er', label="Download enrichRes obj"))),
                 withSpinner(DTOutput("hits_table")), tags$br()
              )
            )
          ) )
        ),


        tabItem(tabName = "tab_cdplot",  ######### CD plot
          box(width=12, title="CD Plot",
              tags$h3(id="cdplot_na", style="font-color: red;",
                      icon("exclamation-triangle"),
                      "Cumulative distribution plots require the use of a DEA input,
                      which you can upload at the input page. You may consult the
                      tutorial for further info."),
              tags$div(id="cdplot_outer", style="display: none;",
                fluidRow(
                  column(8,selectizeInput(inputId="mir_fam", choices=c(),
                                      label="Select miRNA family to display")),
                  column(3,selectInput(inputId="CD_type", "Split by",
                                   choices=c("sites","score"))),
                  column(1, actionButton(inputId="help_cdplot",
                                    icon=icon("question-circle"), label=""))),
                withSpinner(jqui_resizable(plotOutput("cd_plot", width='100%',
                                                      height='400px'))),
                tags$br(), tags$br(), tags$br(), tags$br(),
                box(width=12, title="Plotting options", collapsible=TRUE,
                    collapsed=TRUE,
                  column(6,sliderInput(inputId="CDplot_xaxis",
                                       "logFC to display on x.axis",
                                       min=0, max=8, value=0, step=0.5)),
                  column(6,sliderInput(inputId="CD_k", "Approximate number of sets",
                                       min=2, max=6, value=3, step=1)),
                  column(6, textInput("CDplot_xlabel", "x-axis label",
                                      value="log(foldchange)")),
                  column(6, selectInput("CDplot_theme", "Theme",
                                        choices=ggplot_themes)),
                  column(6, downloadButton('cd_plot_dl', label="Download plot"),
                         actionButton('CDplot_dlContent', label="Download plot R data"))
                )
              )
          )
        ),
        tabItem(tabName="tab_benchmark",
          tabBox(width=12,
            tabPanel("Tests description", .testDescription(),
                     tags$h3("Summary"),
                     fluidRow(column(12, align="center", tableOutput("testsummary") ))),
            tabPanel("Tests benchmark",
              tags$h3("Benchmark of the different target enrichment tests"),
              tags$p("The different tests were benchmarked on different datasets
                     each involving the transcriptomic characterization of the
                     knockdown or over-expression of different miRNAs. For each
                     experiment, the signal was additionally scrambled to create
                     further, more difficult 'pseudo-experiments', which are
                     averaged in the results below. The benchmark was performed
                     using TargetScan (conserved)-predicted sites, and was then
                     used to guide the choice of default tests in the enrichMiR app."),
              tags$img(src="benchmark1.png"),
              tags$p("Panel A shows the rank of the true miRNA according to
                     the different tests (lower=better, i.e. a rank of 1
                     indicates that the true miRNA was correctly identified as
                     the top enriched one). Panel B shows the effective sensitivity
                     and False Discovery Rate (FDR) of the different tests at a
                     nominal q-value threshold of 0.05. One can observe that
                     while most tests manage to rank the true hypothesis as
                     first, most fail to accurately control error."),
              tags$p("In light of these results, the siteoverlap and woverlap
                     tests were selected as the default for binary signals, and
                     the areamir test for continuous signals. ", tags$em("For
                     use with larger annotations (e.g. scanMiR), we however
                     recommend the more conservative lmadd test"), "(see
                     publication for details)."),
              tags$p("Note that restricting the enrichment analysis to the
                     miRNAs expressed in your system systematically decreases
                     FDR. You can do so in the 'Species and miRNAs' tab, either
                     using a custom list of miRNAs or selecting from available
                     tissues.")
            )
          ), tags$div(style="clear: both;")
        )
      )
    )
  )
}