Flame 2.0 update + help pages

README.md

@@ -1,17 +1,32 @@
 # Flame
-A web tool for Functional and Literature Enrichment analysis of multiple sets.
+Visualization and interpretation of functional and literature enrichment analysis results from multiple sets
 
-With Flame one can:<br/>
-* Upload multiple gene/protein lists<br/>
-* Combine lists by calculating their unions and intersections with the help of UpSet plots<br/>
-* Perform functional enrichment analysis on any of the combined lists<br/>
-* Perform literature enrichment analysis on any of the combined lists<br/>
-* Generate protein-protein interaction networks<br/>
-* Visualize and export the functional enrichment results<br/>
-* Explore results with the use of heatmaps, bar charts, Manhattan plots, networks and tables<br/>
-* Perform network analysis and see gene-function, function-function and gene-gene associations<br/>
-* Apply interactive filters on the generated plots<br/>
-* Perform cross-database and cross-species id conversions<br/>
+With Flame one can:
+* Upload multiple gene/protein lists, SNPs, free text or gene expression results (Volcano plot)
+* Combine lists by calculating their unions and intersections with the help of UpSet plots
+* Perform functional enrichment analysis on any of the combined lists for more than 14,000 organisms, using four tools (aGOtool, gProfiler, WebGestalt, enrichR)
+* Combine and compare enrichment results from multiple runs
+* Perform literature enrichment analysis on any of the combined lists, using aGOtool
+* Generate protein-protein interaction networks via STRING
+* Visualize results with the use of networks, heatmaps, bar charts, scatter plots and searchable tables
+* Perform network analysis at the gene-function, function-function and gene-gene association levels
+* Visualize networks in interactive, multi-layered views with Arena3Dweb
+* Combine data sources and apply interactive filters on the generated plots
+* Perform cross-database and cross-species id conversions
+* Utilize our API to connect Flame with external applications
 
+Flame is written in R/Shiny and JavaScript and is available at http://flame.pavlopouloslab.info
 
-Check our publication at https://www.mdpi.com/2079-7737/10/7/665 
+# Installation
+
+* Download and install the Flame image from Docker Hub: https://hub.docker.com/r/pavlopouloslab/flame
+
+* Otherwise, download this GitHub repo and run Flame via RStudio. R (https://www.r-project.org/) and RStudio (https://rstudio.com/) must be installed. Make sure the following R libraries are also installed:
+**shinyjs**, **shinyalert**, **bsplus**, **upsetjs**, **stringr**, **httr**, **httpuv**, **curl**, **jsonlite**, **gprofiler2**, **WebGestaltR**, **shinydashboard**, **shinyWidgets**, **DT**, **tidyr**, **enrichR**, **plotly**, **igraph**, **visNetwork**.
+To start the program, double click on the **Flame.Rproj** file. This opens the RStudio process. Then, open the **server.R** file in RStudio and in the Run App options choose "Run External" and then click Run App.
+
+# Cite
+Thanati, F., Karatzas, E., Baltoumas, F.A., Stravopodis, D.J., Eliopoulos, A.G. and Pavlopoulos, G.A., 2021.
+**FLAME: a web tool for functional and literature enrichment analysis of multiple gene lists.**
+Biology, 10(7), p.665, doi: 10.3390/biology10070665
+https://www.mdpi.com/2079-7737/10/7/665

config/global_settings.R

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+options(shiny.maxRequestSize = 1.0 * 1024^2) # uploaded files < 1MB each

config/global_variables.R

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+# Input ####
+# Volcano
+DEFAULT_VOLCANO_LOG10PVALUE_THRESHOLD <- 1.30103
+DEFAULT_VOLCANO_LOG10PVALUE_STEP <- 0.00001
+DEFAULT_VOLCANO_LOG2FC_THRESHOLD <- 1
+DEFAULT_VOLCANO_LOG2FC_STEP <- 0.001
+
+# Enrichment ####
+ENRICHMENT_TOOLS <- c("aGOtool", "gProfiler", "WebGestalt", "enrichR") # david
+TAB_NAMES <- list(
+  "ALL" = "all",
+  "GO:MF" = "gomf", "GO:CC" = "gocc", "GO:BP" = "gobp",
+  "KEGG" = "kegg", "REAC" = "reac", "WP" = "wp", "PANTHER" = "panther",
+  "INTERPRO" = "interpro", "PFAM" = "pfam", "UNIPROT" = "uniprot",
+  "DO" = "do", "DISGENET" = "disgenet", "OMIM" = "omim", "GLAD4U_DISEASE" = "glad4udisease", "ORPHA" = "orpha",
+  "DRUGBANK" = "drugbank", "GLAD4U_DRUG" = "glad4udrug",
+  "BTO" = "brenda", "WBBT" = "wbbt", "TF" = "tf",
+  "MIRNA" = "mirna", "CORUM" = "corum",
+  "HPA" = "hpa", "HP" = "hp", "WBP" = "wbp", "MGI" = "mgi"
+)
+TAB_NAMES_CODES <- as.character(TAB_NAMES)
+ENRICHMENT_DATASOURCES <- names(TAB_NAMES[TAB_NAMES != "all"])
+NAMESPACES <- list()
+NAMESPACES[["CORE"]] <- list(
+  "ENSEMBL Gene ID" = "ENSG",
+  "ENSEMBL Protein ID" = "ENSP", "ENSEMBL Transcript ID" = "ENST",
+  "Entrez Gene Name" = "ENTREZGENE", "Entrez Gene Accession" = "ENTREZGENE_ACC",
+  "Entrez Gene Transcript Name" = "ENTREZGENE_TRANS_NAME",
+  "UniProt Gene Name" = "UNIPROT_GN", "UniProt Accession" = "UNIPROT_GN_ACC", 
+  "UniProt Archive" = "UNIPARC", "RefSeq Protein Accession" = "REFSEQ_PEPTIDE_ACC",
+  "RefSeq mRNA" = "REFSEQ_MRNA", "RefSeq mRNA Accession" = "REFSEQ_MRNA_ACC",
+  "RefSeq Non-coding RNA Accession" = "REFSEQ_NCRNA_ACC",
+  "EMBL Accession" = "EMBL", "ChEMBL" = "CHEMBL", 
+  "WIKIGENE ID" = "WIKIGENE" 
+)
+NAMESPACES[["SPECIAL"]] <- list()
+NAMESPACES[["SPECIAL"]][["amellifera"]] <- c("BEEBASE" = "BEEBASE")
+NAMESPACES[["SPECIAL"]][["dmelanogaster"]] <- c("FLYBASE_GENE_ID" = "FLYBASE_GENE_ID")
+NAMESPACES[["AGOTOOL"]] <- list("ENSEMBL Protein ID" = "ENSP")
+UI_TERM_KEYWORD <- list(
+  "functional" = "functions", "literature" = "articles"
+)
+
+# Plots ####
+# Network
+NETWORK_IDS <- c("network1", "network2", "network3")
+LAYOUT_CHOICES <- list(
+  `layout_with_graphopt` = "Graph Opt", `layout_nicely`= "Fruchterman-Reingold",
+  `layout_with_kk`= "Kamada-Kawai", `layout_with_mds` = "Multi-dimensional Scaling",
+  `layout_as_tree` = "Tree", `layout_as_star`  =	"Star",
+  `layout_in_circle`  =	"Circle", `layout_on_grid` = "Grid",
+  `layout_randomly`  =	"Random"
+)
+# Heatmap
+HEATMAP_IDS <- c("heatmap1", "heatmap2", "heatmap3")
+# Colors
+GENE_NODE_COLOR <- "#d1e1d9"
+LITERATURE_NODE_COLOR <- "#cc9f9f"
+DATASOURCE_COLORS <- c(
+  "GO:MF" = "#dc3912", "GO:BP" = "#ff9900", "GO:CC" = "#109618",
+  "KEGG" = "#dd4477", "REAC" = "#3366cc", "WP" = "#0099c6", "PANTHER" = "#634341",
+  "INTERPRO" = "#8a5103", "PFAM" = "#b3b000", "UNIPROT" = "#55edeb",
+  "DO" = "#f7c8fa", "DISGENET" = "#c0f0a1", "OMIM" = "#edebaf",
+  "GLAD4U_DISEASE" = "#9f86d9", "ORPHA" = "#03fcc6", "DRUGBANK" = "#7d4a74", "GLAD4U_DRUG" = "#4a9091",
+  "BTO" = "#f0d871", "WBBT" = "#9cb59c", "TF" = "#5574a6", "MIRNA" = "#22aa99",
+  "CORUM" = "#66aa00", "HPA" = "#6633cc", "HP" = "#990099", "WBP" = "#fffd78", "MGI" = "#fc4503",
+  "PUBMED" = LITERATURE_NODE_COLOR, "GENE" = GENE_NODE_COLOR
+)
+

config/server_variables.R

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+# Input ####
+LISTNAME_NCHAR_LIMIT <- 100
+LIST_LIMIT <- 10
+GENE_LIST_LIMIT <- 3000
+OBJECT_SIZE_LIMIT <- 1000000 # bytes, 1MB
+STRING_LIMIT <- 500
+RANDOM_GENES_NUMBER <- 200 # currently 674 max # enrichR::genes790 
+GENE_LIST_PREFIX <- "gene_list"
+# Volcano
+VOLCANO_COLORS <- c("default" = "#000000",
+                    "overexpressed" = "#eb6e6c", "underexpressed" = "#64e4ed")
+
+# Organisms ####
+ORGANISMS <- readRDS("./organisms/organismsDF.RDS")
+TOOL_ORGANISMS <- readRDS("./organisms/toolOrganismsList.RDS")
+SPECIAL_ORGANISMS <- c("amellifera", "dmelanogaster")
+SPECIAL_PREFERRED_TOOL <- list()
+SPECIAL_PREFERRED_TOOL[["amellifera"]] <- "gProfiler"
+SPECIAL_PREFERRED_TOOL[["dmelanogaster"]] <- "enrichR"
+SPECIAL_PREFERRED_NAMESPACE <- list()
+SPECIAL_PREFERRED_NAMESPACE[["amellifera"]] <- "BEEBASE"
+SPECIAL_PREFERRED_NAMESPACE[["dmelanogaster"]] <- "USERINPUT"
+
+# Enrichment ####
+ENRICHMENT_TYPES <- c("functional", "literature")
+DATASOURCES_PRINT <- list(
+  'Gene Ontology' = list(
+    "Molecular Function (GO:MF)" = "GO:MF",
+    "Cellular Component (GO:CC)" = "GO:CC",
+    "Biological Process (GO:BP)" = "GO:BP"
+  ),
+  'Biological Pathways' = list(
+    "KEGG" = "KEGG", "Reactome" = "REAC",
+    "WikiPathways" = "WP", "PANTHER" = "PANTHER"
+  ),
+  'Diseases' = list(
+    "Disease Ontology" = "DO", "DisGeNET" = "DISGENET",
+    "OMIM" = "OMIM", "GLAD4U" = "GLAD4U_DISEASE", "Orphanet" = "ORPHA"
+  ),
+  'Proteins' = list(
+    "Interpro" = "INTERPRO", "PFAM" = "PFAM",
+    "UniProt keywords" = "UNIPROT",
+    "CORUM"= "CORUM"
+  ),
+  'Phenotypes' = list(
+    "Human Phenotype Ontology" = "HP",
+    "MGI Mammalian Phenotype" = "MGI",
+    "WormBase Phenotypes" = "WBP"
+  ),
+  'Tissues' = list(
+    "Human Protein Atlas (HPA)" = "HPA",
+    "Brenda Tissue Ontology" = "BTO",
+    "WormBase Anatomic Associations Ontology" = "WBBT"
+  ),
+  'Drugs' = list(
+    "DrugBank" = "DRUGBANK",
+    "GLAD4U" = "GLAD4U_DRUG"
+  ),
+  'Regulatory motifs in DNA' = list(
+    "TRANSFAC" = "TF", "miRTarBase" = "MIRNA"
+  )
+)
+DATASOURCES_DEFAULT_SELECTED <- list("GO:MF", "GO:CC", "GO:BP", "KEGG")
+DATASOURCES <- list() # gProfiler here, the rest through an init.R function
+DATASOURCES[["GPROFILER"]] <- c("GO:MF", "GO:CC", "GO:BP",
+                              "KEGG", "REAC", "WP",
+                              "TF", "MIRNA", "CORUM", "HPA", "HP")
+DATASOURCES_CODES <- list()
+DATASOURCES_CODES[["AGOTOOL"]] <- list(
+  "GO:MF" = -23, "GO:CC" = -22, "GO:BP" = -21,
+  "KEGG" = -52, "REAC" = -57, "WP" = -58,
+  "INTERPRO" = -54, "PFAM" = -55, "UNIPROT" = -51,
+  "DO" = -26, "BTO" = -25,
+  "PUBMED" = -56
+)
+DATASOURCES_CODES[["WEBGESTALT"]] <- list(
+  "GO:MF" = "geneontology_Molecular_Function_noRedundant",
+  "GO:CC" = "geneontology_Cellular_Component_noRedundant",
+  "GO:BP" = "geneontology_Biological_Process_noRedundant",
+  "KEGG" = "pathway_KEGG",
+  "REAC" = "pathway_Reactome",
+  "WP" = "pathway_Wikipathway",
+  "PANTHER" = "pathway_Panther",
+  "DISGENET" = "disease_Disgenet",
+  "OMIM" = "disease_OMIM",
+  "GLAD4U_DISEASE" = "disease_GLAD4U",
+  "DRUGBANK" = "drug_DrugBank",
+  "GLAD4U_DRUG" = "drug_GLAD4U",
+  "HP" = "phenotype_Human_Phenotype_Ontology"
+)
+DATASOURCES_CODES[["ENRICHR"]] <- list(
+  "GO:MF" = "GO_Molecular_Function_2021",
+  "GO:CC" = "GO_Cellular_Component_2021",
+  "GO:BP" = "GO_Biological_Process_2021",
+  "KEGG" = "KEGG_2016", # "KEGG_2021_Human" -> doesn't return Ids
+  "REAC" = "Reactome_2022",
+  "WP" = "WikiPathway_2021_Human",
+  "PANTHER" = "Panther_2016",
+  "HP" = "Human_Phenotype_Ontology"
+)
+DATASOURCES_CODES[["MOUSE_ENRICHR"]] <- list(
+  "GO:MF" = "GO_Molecular_Function_2021",
+  "GO:CC" = "GO_Cellular_Component_2021",
+  "GO:BP" = "GO_Biological_Process_2021",
+  "WP" = "WikiPathways_2019_Mouse",
+  "MGI" = "KOMP2_Mouse_Phenotypes_2022"
+)
+DATASOURCES_CODES[["FLY_ENRICHR"]] <-
+  DATASOURCES_CODES[["FISH_ENRICHR"]] <- list(
+    "GO:MF" = "GO_Molecular_Function_2018",
+    "GO:CC" = "GO_Cellular_Component_2018",
+    "GO:BP" = "GO_Biological_Process_2018",
+    "WP" = "WikiPathways_2018"
+  )
+DATASOURCES_CODES[["YEAST_ENRICHR"]] <- list(
+  "GO:MF" = "GO_Molecular_Function_2018",
+  "GO:CC" = "GO_Cellular_Component_2018",
+  "GO:BP" = "GO_Biological_Process_2018",
+  "WP" = "WikiPathways_2018",
+  "KEGG" = "KEGG_2018"
+)
+DATASOURCES_CODES[["WORM_ENRICHR"]] <- list(
+  "GO:MF" = "GO_Molecular_Function_2018",
+  "GO:CC" = "GO_Cellular_Component_2018",
+  "GO:BP" = "GO_Biological_Process_2018",
+  "WP" = "WikiPathways_2018",
+  "DO" = "Human_Diseases_from_WormBase_2018",
+  "WBP" = "Phenotypes_WormBase_2018",
+  "WBBT" = "Anatomic_Associations_WormBase_2018"
+)
+DATASOURCES_CODES[["OX_ENRICHR"]] <- list(
+  "GO:MF" = "GO_Molecular_Function_2021",
+  "GO:CC" = "GO_Cellular_Component_2021",
+  "GO:BP" = "GO_Biological_Process_2021",
+  "REAC" = "Reactome_2016",
+  "WP" = "WikiPathway_2021_Human",
+  "ORPHA" = "Orphanet_Augmented_2021",
+  "HP" = "Human_Phenotype_Ontology",
+  "MGI" = "MGI_Mammalian_Phenotype_Level_4_2019"
+)
+NAMESPACES[["GPROFILER"]] <- c("User Input" = "USERINPUT", NAMESPACES[["CORE"]])
+NAMESPACES[["WEBGESTALT"]] <- list(
+  "Entrez Gene Accession" = "ENTREZGENE_ACC",
+  "User Input" = "USERINPUT"
+)
+NAMESPACES[["ENRICHR"]] <- list(
+  "Entrez Gene Name" = "ENTREZGENE",
+  "User Input" = "USERINPUT"
+)
+NAMESPACES[["FLY_ENRICHR"]] <-
+  NAMESPACES[["YEAST_ENRICHR"]] <- list(
+  "User Input" = "USERINPUT"
+)
+DEFAULT_NAMESPACE_TEXT <- "Default tool namespace conversions"
+METRICS <- list()
+METRICS[["AGOTOOL"]] <- list("False discovery rate", "P-value")
+METRICS[["GPROFILER"]] <- list(
+  "g:SCS threshold" = "gSCS",
+  "False discovery rate" = "fdr",
+  "Bonferroni correction" = "bonferroni"
+)
+METRICS[["WEBGESTALT"]] <- list(
+  "Benjamini-Hochberg" = "BH",
+  "Benjamini-Yekutieli" = "BY",
+  "Holm" = "holm",
+  "Hochberg" = "hochberg",
+  "Hommel" = "hommel",
+  "Bonferroni adjustment" = "bonferroni"
+)
+METRICS[["ENRICHR"]] <- list("Adjusted P-value" = "adjusted_pvalue")
+DEFAULT_METRIC_TEXT <- "Default tool metrics"
+ENRICHMENT_DF_COLNAMES <- c(
+  "Source", "Term_ID", "Function", "P-value", "Term Size", 
+  "Query size", "Intersection Size", "Positive Hits"
+)
+AGOTOOL_API_LINK <- "https://agotool.org/api_orig"
+
+# Plots ####
+ALL_PLOT_IDS <- c(NETWORK_IDS, HEATMAP_IDS, "barchart", "scatterPlot")
+DEFAULT_SLIDER_VALUE <- 50
+MAX_SLIDER_VALUE <- 200
+SINGLE_BAR_HEIGHT_PX <- 18
+MIN_BAR_HEIGHT_PX <- 200
+EDGE_WIDTH_MIN <- 0.1
+EDGE_WIDTH_MAX <- 3
+
+# Interoperability ####
+POST_REQUEST_PATH <- 'tmp/'
+ARENA_API_LINK <- "https://bib.fleming.gr/bib/api/arena3dweb" #"http://127.0.0.1:8080/api/arena3dweb"
+ARENA_LAYER_SPACING_PIXELS <- 300
+ARENA_Y_Z_SAMPLING_LIMIT <- 410

config/static_variables.R

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+# Input
+userInputLists <- list()
+checkedListNames <- list() # in combination with js_listNames 
+volcanoSelectedItems <- c()
+
+# Enrichment
+enrichmentResults <- list()
+arenaEdgelist <- list()
+gprofilerResult <- list() # for gprofiler ManhattanPlot only
+combinationResult <- data.frame()
+
+# Current
+currentVariantResults <- data.frame()
+currentTextminingResult <- c()
+currentVolcano <- data.frame()
+currentUpsetMode <- ""
+
+currentUserList <- c()
+currentEnrichmentType <- ""
+currentOrganism <- ""
+currentEnrichmentTool <- ""
+currentType_Tool <- ""
+currentNamespace <- ""
+currentSignificanceMetric <- ""

config/ui_variables.R

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+# Enrichment ####
+DEFAULT_TOOL <- "aGOtool"
+DEFAULT_TOOL_UPPER <- toupper(DEFAULT_TOOL)
+AGOTOOL_DATASOURCES_PRINT_LITERATURE <- list("PubMed Publications" = "PUBMED")
+
+# Plots ####
+PLOT_TABNAMES <- c("Network", "Heatmap", "Barchart", "Scatter Plot", "Manhattan")
+# Network 
+LEGEND_ITEMS <- list(
+  list("GO:MF", "GO:BP", "GO:CC","UNIPROT"),
+  list("KEGG", "REAC", "WP", "PANTHER"),
+  list("DO", "DISGENET", "OMIM", "GLAD4U_DISEASE", "ORPHA"),
+  list("DRUGBANK", "GLAD4U_DRUG", "INTERPRO", "PFAM", "PUBMED"),
+  list("BTO", "WBBT", "TF", "MIRNA", "CORUM"),
+  list("HPA", "HP", "WBP", "MGI", "GENE")
+)
+VIS_NET_HEIGHT <- "850px"
+
+# About ####
+YEAR <- substr(Sys.Date(), 1, 4)