scAgeComShiny: A Shiny App for scAgeCom

#' introduction UI Function
#'
#' @description A shiny Module.
#'
#' @param id,input,output,session Internal parameters for {shiny}.
#'
#' @noRd 
#'
#' @importFrom shiny NS tagList 
mod_introduction_ui <- function(id) {
  ns <- NS(id)
  uiOutput(ns("INTRO_PAGE_VIEW"))
}

#' introduction Server Functions
#'
#' @noRd 
mod_introduction_server <- function(id) {
  moduleServer(
    id,
    function(
      input,
      output,
      session
    ) {
      ns <- session$ns
      
      ## define style to be reused multiple times ####
      
      style_intro_accordion_title <- paste(
        "font-size: 20px;",
        "margin-top: 0;",
        "margin-bottom: 0;"
      )
      style_intro_accordion_text <- paste(
        "margin:auto;",
        "font-size: 15px;",
        "text-align: justify;"
      )
      
      ## outputs #####
      
      output$INTRO_PAGE_VIEW <- renderUI({
        fluidPage(
          fluidRow(
            column(
              width = 6,
              offset = 3,
              titlePanel(htmlOutput(ns("INTRO_TITLE")))
            )
          ),
          fluidRow(
            column(
              width = 8,
              offset = 2,
              htmlOutput(ns("INTRO_OVERVIEW"))
            )
          ),
          fluidRow(
            column(
              width = 8,
              offset = 2,
              {
                intro_accordion <-  bsplus::bs_accordion(
                  id = "INTRO_METHOD_DETAIL"
                ) %>%
                  bsplus::bs_append(
                    title = htmlOutput(ns("INTRO_CODE_TITLE")),
                    content = htmlOutput(ns("INTRO_CODE_TEXT"))
                  ) %>%
                  bsplus::bs_append(
                    title = htmlOutput(ns("INTRO_SCRNA_TITLE")),
                    content = htmlOutput(ns("INTRO_SCRNA_TEXT"))
                  ) %>%
                  bsplus::bs_append(
                    title = htmlOutput(ns("INTRO_LRI_TITLE")),
                    content = uiOutput(ns("INTRO_LRI_CONTENT"))
                  ) %>%
                  bsplus::bs_append(
                    title = htmlOutput(ns("INTRO_ABOUT_TITLE")),
                    content = htmlOutput(ns("INTRO_ABOUT_TEXT"))
                  )
                attrib_ <- intro_accordion$children[[1]]$children[[2]]$attribs
                attrib_[which(attrib_ == "in")] <- NULL
                intro_accordion$children[[1]]$children[[2]]$attribs <- attrib_
                intro_accordion
              },
              style = "padding: 10px"
            )
          )
        )
      })
      
      output$INTRO_TITLE <- renderUI({
        tags$p(
          style = paste(
            "margin: 20px auto;",
            "font-size: 26px;",
            "text-align: center;"
          ),
          "Welcome to scAgeCom!"
        )
      })
      
      output$INTRO_OVERVIEW <- renderUI({
        tags$div(
          style = paste(
            "margin:auto;",
            "font-size: 15px;",
            "text-align: justify;"
          ),
          tags$p(
            tags$b(
              paste(
                "This project is a comprehensive analysis of changes occurring",
                "with age in mouse intercellular communication. The Atlas was",
                "built by applying our R package scDiffCom to publicly",
                "available scRNA-seq datasets. We provide tissue-specific",
                "results for 23 organs as well as a global comparison of",
                "changes across tissues."
              )
            )
          )
        )
      })
      
      output$INTRO_CODE_TITLE<- renderUI({
        tags$h3(
          style = style_intro_accordion_title,
          "Methodology and Code",
        )
      })
      
      output$INTRO_CODE_TEXT <- renderUI({
        tags$div(
          style = style_intro_accordion_text,
          tags$h4("The package"),
          tags$p(
            "We developed the R package",
            tags$a(
              href = "https://github.com/CyrilLagger/scDiffCom",
              "scDiffCom",
              target = "_blank"
            ),
            paste(
              "to investigate how intercellular communication varies between",
              "two biological conditions of interest (young/old, sick/healthy, etc.).",
              "Here, we used scDiffCom to study differences in intercellular",
              "comunication between young and old murine cells. Please visit"
            ),
            tags$a(
              href = "https://cyrillagger.github.io/scDiffCom/articles/scDiffCom-vignette.html",
              "this tutorial",
              target = "_blank"
            ),
            "to apply this package to your own data."
          ),
          tags$h4("How does it work?"),
          tags$p(
            paste(
              "scDiffCom can be applied to any scRNA-seq "
            ),
            tags$a(
              href = "https://satijalab.org/seurat/index.html",
              "Seurat object",
              target = "_blank",
              .noWS = "outside"
            ),
            paste(
              ". It uses its own integrated database of ligand-receptor interactions",
              "to list all the potential signals between the cell types of the dataset.",
              "Statistical tests are then performed to only retain biologically",
              "significant interactions and to assess how they change between",
              "the two conditions. Finally, an over-representation test allows the",
              "package to infer the dominant",
              "changing patterns on a gene-centric, cell type-centric or",
              "functional-centric (GO/KEGG) level."
            )
          ),
          tags$img(
            src = "img/figure_workflow.png",
            style = "display: block; margin-left: auto; margin-right: auto; width: 100%; max-width: 630px;"
          ),
          tags$h4("Find our scripts on GitHub"),
          tags$ul(
            tags$li(
              "R package for differential analysis:",
              tags$a(
                href = "https://github.com/CyrilLagger/scDiffCom",
                "scDiffCom",
                target = "_blank"
              )
            ),
            tags$li(
              "Code for this aging analysis:",
              tags$a(
                href = "https://github.com/CyrilLagger/scAgeCom",
                "scAgeCom",
                target = "_blank"
              )
            ),
            tags$li(
              "Code for this website:",
              tags$a(
                href = "https://github.com/CyrilLagger/scAgeComShiny",
                "scAgeComShiny",
                target = "_blank"
              )
            )
          )
        )
      })
      
      output$INTRO_SCRNA_TITLE <- renderUI({
        tags$h3(
          style = style_intro_accordion_title,
          "Aging Single Cell Datasets"
        )
      })
      
      output$INTRO_SCRNA_TEXT <- renderUI({
        fluidPage(
          fluidRow(
            column(
              width = 12,
              tags$div(
                style = style_intro_accordion_text,
                tags$p(
                  paste(
                    "We built this Atlas from several murine scRNA-seq datasets",
                    "provided by "
                  ),
                  tags$a(
                    href = "https://tabula-muris-senis.ds.czbiohub.org/",
                    "Tabula Muris Senis",
                    target = "_blank",
                    .noWS = "outside"
                  ),
                  paste(" ("),
                  tags$a(
                    href = "https://www.nature.com/articles/s41586-020-2496-1",
                    "Nature article",
                    target = "_blank",
                    .noWS = "outside"
                  ),
                  paste(") and "),
                  tags$a(
                    href = "https://mca.research.calicolabs.com/",
                    "Calico's Murine aging cell atlas",
                    target = "_blank",
                    .noWS = "outside"
                  ),
                  paste(" ("),
                  tags$a(
                    href = "https://genome.cshlp.org/content/29/12/2088",
                    "Genome Research article",
                    target = "_blank",
                    .noWS = "outside"
                  ),
                  paste(
                    "). After pre-processing, we retained 58 datasets across",
                    "23 tissues and 5 sex/experimental conditions:"
                  )
                )
              )
            )
          ),
          fluidRow(
            column(
              width = 12,
              htmlOutput(ns("INTRO_SCRNA_HTML_FIG"))
            )
          )
        )
      })
      
      output$INTRO_SCRNA_HTML_FIG <- renderUI({
        tags$div(
          tags$img(
            src = "img/figure_dataset.png",
            style = "display: block; margin-left: auto; margin-right: auto; width: 100%; max-width: 630px;"
          )
        )
      })
      
      output$INTRO_LRI_TITLE <- renderUI({
        tags$h3(
          style = style_intro_accordion_title,
          "Collection of Ligand-Receptor Interactions"
        )
      })
      
      output$INTRO_LRI_CONTENT <- renderUI({
        fluidPage(
          fluidRow(
            column(
              width = 6,
              htmlOutput(ns("INTRO_LRI_HTML_TEXT"))
            ),
            column(
              width = 6,
              htmlOutput(ns("INTRO_LRI_HTML_DB_LIST"))
            )
          ),
          fluidRow(
            column(
              width = 12,
              DT::dataTableOutput(ns("INTRO_LRI_TABLE"))
            )
          ),
          fluidRow(
            column(
              width = 12,
              htmlOutput(ns("INTRO_LRI_UPSET_PLOT"))
            )
          )
        )
      })
      
      output$INTRO_LRI_HTML_TEXT <- renderUI({
        tags$div(
          style = style_intro_accordion_text,
          tags$p(
            "scDiffCom internally relies on a list of ligand-receptor interactions",
            "that we have processed and combined from the seven studies in the list",
            "opposite. We carefully took into account the interactions involving",
            "heteromeric complexes."
          ),
          tags$p(
            "You will find below the mouse interactions used for the scAgeCom analysis.",
            "This table and its human equivalent can also be accessed",
            "from our package scDiffcom."
          )
        )
      })
      
      output$INTRO_LRI_HTML_DB_LIST <- renderUI({
        tags$ul(
          tags$li(
            "CellChat:",
            tags$a(
              href = "http://www.cellchat.org/", "webpage",
              target = "_blank"
            ),
            " and ",
            tags$a(
              href = "https://www.nature.com/articles/s41467-021-21246-9",
              "Nature Communications article",
              target = "_blank",
              .noWS = "outside"
            ),
            "."
          ),
          tags$li(
            "CellPhoneDB:",
            tags$a(
              href = "https://www.cellphonedb.org/",
              "webpage",
              target = "_blank"
            ),
            " and ",
            tags$a(
              href = "https://www.nature.com/articles/s41596-020-0292-x",
              "Nature Protocol article",
              target = "_blank",
              .noWS = "outside"
            ),
            "."
          ),
          tags$li(
            "CellTalkDB:",
            tags$a(
              href = "http://tcm.zju.edu.cn/celltalkdb/",
              "webpage",
              target = "_blank"
            ),
            " and ",
            tags$a(
              href = "https://academic.oup.com/bib/advance-article-abstract/doi/10.1093/bib/bbaa269/5955941",
              "Briefings in Bioinformatics article",
              target = "_blank",
              .noWS = "outside"
            )
          ),
          tags$li(
            "connectomeDB2020:",
            tags$a(
              href = "https://github.com/forrest-lab/NATMI",
              "webpage",
              target = "_blank"
            ),
            " and ",
            tags$a(
              href = "https://www.nature.com/articles/s41467-020-18873-z",
              "Nature Communications article",
              target = "_blank",
              .noWS = "outside"
            ),
            "."
          ),
          tags$li(
            "ICELLNET:",
            tags$a(
              href = "https://github.com/soumelis-lab/ICELLNET",
              "webpage",
              target = "_blank"
            ),
            " and ",
            tags$a(
              href = "https://www.nature.com/articles/s41467-021-21244-x",
              "Nature Communications article",
              target = "_blank",
              .noWS = "outside"
            ),
            "."
          ),
          tags$li(
            "NicheNet:",
            tags$a(
              href = "https://github.com/saeyslab/nichenetr",
              "webpage",
              target = "_blank"
            ),
            " and ",
            tags$a(
              href = "https://www.nature.com/articles/s41592-019-0667-5",
              "Nature Methods article",
              target = "_blank",
              .noWS = "outside"
            ),
            "."
          ),
          tags$li(
            "SingleCellSignalR:",
            tags$a(
              href = "http://www.bioconductor.org/packages/release/bioc/html/SingleCellSignalR.html",
              "webpage",
              target = "_blank"
            ),
            " and ",
            tags$a(
              href = "https://academic.oup.com/nar/article/48/10/e55/5810485",
              "Nucleic Acids Research article",
              target = "_blank",
              .noWS = "outside"
            ),
            "."
          )
        )
      })
      
      output$INTRO_LRI_TABLE <- DT::renderDataTable({
        display_LRI_table(
          LRI_table = scAgeComShiny::scAgeCom_data$LRI_mouse_curated,
          LRI_database = scAgeComShiny::scAgeCom_data$LRI_DATABASES
        )
      })
      
      output$INTRO_LRI_UPSET_PLOT <- renderUI({
        tags$div(
          tags$img(
            src = "img/upset_LRI_mouse_shiny.png",
            style = "display: block; margin-left: auto; margin-right: auto; width: 100%; max-width: 800px;"
          )
        )
      })

      output$INTRO_ABOUT_TITLE <- renderUI({
        tags$h3(
          style = style_intro_accordion_title,
          "Contact"
        )
      })
      
      output$INTRO_ABOUT_TEXT <- renderUI({
        tags$div(
          style = style_intro_accordion_text,
          tags$p(
            paste(
              "For questions, issues or comments, please contact Cyril Lagger",
              "(lagger.cyril@gmail.com) or Joao Pedro de Magalhaes",
              "(aging@liverpool.ac.uk)."
            )
          )
        )
      })
      
    })
}

display_LRI_table <- function(
  LRI_table,
  LRI_database
) {
  `Database(s) of Origin` <- NULL
  dt <- LRI_table[
    apply(
      sapply(
        LRI_database,
        function(i) {
          grepl(i, `Database(s) of Origin`)
        }
      ),
      MARGIN = 1,
      any
    )
  ]
  DT::datatable(
    data = dt[, 1:7],
    class = "display compact",
    options = list(
      pageLength = 10,
      dom = '<"top"f>rt<"bottom"lip><"clear">',
      columnDefs = list(
        list(
          targets = c(6,7),
          render = htmlwidgets::JS(
            "function(data, type, row, meta) {",
            "return type === 'display' && data.length > 20 ?",
            "'<span title=\"' + data + '\">' + data.substr(0, 20) + '...</span>' : data;",
            "}"
          )
        )
      )
    ),
    caption = tags$caption(
      style = paste(
        "caption-side: top;",
        "text-align: center;",
        "color: black;",
        "font-size: 130%;"
      ),
      "Table of Mouse Ligand-Receptor Interactions"
    )
  )
}