Chapter 8 Create Enrichment map from R with g:Profiler results

8.1 Initialize variables and libraries

#use library
#make sure biocManager is installed
tryCatch(expr = { library("BiocManager")}, 
         error = function(e) { 
           install.packages("BiocManager")}, 
         finally = library("BiocManager"))

tryCatch(expr = { library("ggplot2")}, 
         error = function(e) { install.packages("ggplot2")}, 
         finally = library("ggplot2"))

#use easy cyRest library to communicate with cytoscape.
tryCatch(expr = { library("RCy3")}, 
         error = function(e) { BiocManager::install("RCy3")}, 
         finally = library("RCy3"))

tryCatch(expr = { library("httr")}, 
         error = function(e) { BiocManager::install("httr")}, 
         finally = library("httr"))

8.2 Configurable Parameters

# is_docker - true/false depending on if you are running R from docker
is_docker <- TRUE

#directory where all the original input data file are
# for example ./data/
working_dir <- "./data/"


#directory where all the generated data files are found.
# For example - ./generated_data/
# If you are using all the notebooks from this set the generated data will be
# put in the ./generated_data folder.  You have to specify if it is gsea or 
# gprofiler
output_dir <- "./generated_data/g_profiler"


#defined threshold for gprofiler enrichments 
#p-value to filter all the genesets.  For example -   1.0
pvalue_gprofiler_threshold <- 1.0

#q-value to filter all the genesets.  For example -   0.05
qvalue_gprofiler_threshold <- 0.001

#similarity threshold to filter all the genesets connections/edges.  
# For example -   0.375
similarity_threshold <- "0.35"

#similarity metric to filter all the genesets connections/edges 
# (can be OVERLAP, JACCARD, or COMBINED.   For example -   Combined
similarity_metric = "JACCARD"

8.3 Specify Data files

Depending on whether you are creating your enrichment map from g:Profiler or GSEA results the sets of files might be a little different. Minimally, you will need to specify: * gmt file * enrichment results file

We have multiple g:profiler results.
* varied geneset size limit ( 250, 1000 or 10,000) * varied geneset sources - baderlab genesets or g:profiler sets.

#get the newest gprofiler gmt file
gprof_files <- file.info(list.files(file.path(getwd(),output_dir),
                                    pattern = "gprofiler_full",
                                    full.names = TRUE) )
gmt_gprofiler_file <- rownames(gprof_files)[which.max(gprof_files$mtime)]
#gmt_gprofiler_file<-file.path(getwd(),output_dir,
#                "gprofiler_full_hsapiens_e109_eg56_p17_1d3191d_.name.gmt")

gprofiler_results_filename1 <-file.path(getwd(),output_dir,
                "gProfiler_hsapiens_lab2_results_GEM_termmin3_max250.gem.txt")

gprofiler_results_filename2 <-file.path(getwd(),output_dir,
                "gProfiler_hsapiens_lab2_results_GEM_termmin3_max10000.gem.txt")


current_network_name <- paste("gprofiler_max250",pvalue_gprofiler_threshold,
                              qvalue_gprofiler_threshold,sep="_")

8.4 Launch Cytoscape

Launch Cytoscape (by default cytoscape will automatically enable rest so as long as cytoscape 3.3 or higher is open R should be able to communicate with it). Make sure if you get an message asking you if you want communicate with other apps that you select “Allow”.

8.5 Make sure you can connect to Cytoscape

if(is_docker){
  current_base = "host.docker.internal:1234/v1"
  .defaultBaseUrl <- "http://host.docker.internal:1234/v1"
} else{
  current_base = "localhost:1234/v1"
}

cytoscapePing (base.url = current_base)

## You are connected to Cytoscape!

cytoscapeVersionInfo (base.url = current_base)

##       apiVersion cytoscapeVersion 
##             "v1"         "3.10.2"

---

8.6 Create an Enrichment map

If you are running R from within a docker you need to first upload your datafiles to Cytoscape before you can create your enrichment map

#if using docker we need to replace all the the paths to the host path
if(is_docker) {
  upload_em_file <- function(localPath) {
    bname <- basename(localPath)
    r <- POST(
      url = 
paste('http://host.docker.internal:1234/enrichmentmap/textfileupload?fileName=', 
                  bname, sep=""),
      config = list(),
      body = list(file = upload_file(localPath)),
      encode = "multipart",
      handle = NULL
    )
    content(r,"parsed")$path
  }
  
  # "upload" the files to the host machine and replace each path with the 
  # host machine path
   gmt_gprofiler_file <- upload_em_file(gmt_gprofiler_file)
  gprofiler_results_filename1 <- upload_em_file(gprofiler_results_filename1)
  gprofiler_results_filename2 <- upload_em_file(gprofiler_results_filename2)
}

---

8.7 Create an Enrichment map - run EM command

#######################################
#create EM

em_command = paste('enrichmentmap build analysisType="generic" gmtFile=',
                   gmt_gprofiler_file,
                   'pvalue=',pvalue_gprofiler_threshold, 
                   'qvalue=',qvalue_gprofiler_threshold,
                   'similaritycutoff=',similarity_threshold,
                   'coefficients=',similarity_metric,
                   'enrichmentsDataset1=',gprofiler_results_filename1, 
                   'enrichmentsDataset2=',gprofiler_results_filename2,
                   'gmtFile=',gmt_gprofiler_file,
                   'filterByExpressions=false',
                   sep=" ")

#enrichment map command will return the suid of newly created network.
response <- commandsGET(em_command,base.url = current_base)

current_network_suid <- 0
#enrichment map command will return the suid of newly created network 
# unless it Failed.  If it failed it will contain the word failed
if(grepl(pattern="Failed", response)){
  paste(response)
} else {
  current_network_suid <- response
}

#check to see if the network name is unique
current_names <- getNetworkList(base.url = current_base)
if(current_network_name %in% current_names){
  #if the name already exists in the network names then put the SUID in front
  # of the name (this does not work if you put the suid at the end of the name)
  current_network_name <- paste(current_network_suid,
                                current_network_name,  sep="_")
}
response <- renameNetwork(title=current_network_name, 
                       network = as.numeric(current_network_suid),
                       base.url = current_base)

8.8 Get a screen shot of the initial network.

#you can only output the file if it isn't on docker
#on docker is put it into the user's home directory with docker has not access to
if(!is_docker){
  output_network_file <- file.path(getwd(),"initial_screenshot_network.png")
  output_network_file_current <- output_network_file

  fitContent()

  if(file.exists(output_network_file)){
    #cytoscape hangs waiting for user response if file already exists.  
    # Remove it first
    response <- file.remove(output_network_file)
  } 

  response <- exportImage(output_network_file, type = "png",
                          base.url = current_base)
}

Change the files and create all the different networks we generated in class in Cytoscape.