R: Wrapper Function for pathfindR - Active-Subnetwork-Oriented...

run_pathfindR {pathfindR}

R Documentation

Wrapper Function for pathfindR - Active-Subnetwork-Oriented Enrichment Workflow

Description

run_pathfindR is the wrapper function for the pathfindR workflow

Usage

run_pathfindR(
  input,
  gene_sets = "KEGG",
  min_gset_size = 10,
  max_gset_size = 300,
  custom_genes = NULL,
  custom_descriptions = NULL,
  pin_name_path = "Biogrid",
  p_val_threshold = 0.05,
  enrichment_threshold = 0.05,
  convert2alias = TRUE,
  plot_enrichment_chart = TRUE,
  output_dir = NULL,
  list_active_snw_genes = FALSE,
  ...
)

Arguments

`input`	the input data that pathfindR uses. The input must be a data frame with three columns: Gene Symbol (Gene Symbol) Change value, e.g. log(fold change) (OPTIONAL) p value, e.g. adjusted p value associated with differential expression
`gene_sets`	Name of the gene sets to be used for enrichment analysis. Available gene sets are 'KEGG', 'Reactome', 'BioCarta', 'GO-All', 'GO-BP', 'GO-CC', 'GO-MF', 'cell_markers', 'mmu_KEGG' or 'Custom'. If 'Custom', the arguments `custom_genes` and `custom_descriptions` must be specified. (Default = 'KEGG')
`min_gset_size`	minimum number of genes a term must contain (default = 10)
`max_gset_size`	maximum number of genes a term must contain (default = 300)
`custom_genes`	a list containing the genes involved in each custom term. Each element is a vector of gene symbols located in the given custom term. Names should correspond to the IDs of the custom terms.
`custom_descriptions`	A vector containing the descriptions for each custom term. Names of the vector should correspond to the IDs of the custom terms.
`pin_name_path`	Name of the chosen PIN or absolute/path/to/PIN.sif. If PIN name, must be one of c('Biogrid', 'STRING', 'GeneMania', 'IntAct', 'KEGG', 'mmu_STRING'). If path/to/PIN.sif, the file must comply with the PIN specifications. (Default = 'Biogrid')
`p_val_threshold`	the p value threshold to use when filtering the input data frame. Must a numeric value between 0 and 1. (default = 0.05)
`enrichment_threshold`	adjusted-p value threshold used when filtering enrichment results (default = 0.05)
`convert2alias`	boolean to indicate whether or not to convert gene symbols in the input that are not found in the PIN to an alias symbol found in the PIN (default = TRUE) IMPORTANT NOTE: the conversion uses human gene symbols/alias symbols.
`plot_enrichment_chart`	boolean value. If TRUE, a bubble chart displaying the enrichment results is plotted. (default = TRUE)
`output_dir`	the directory to be created where the output and intermediate files are saved (default = `NULL`, a temporary directory is used)
`list_active_snw_genes`	boolean value indicating whether or not to report the non-significant active subnetwork genes for the active subnetwork which was enriched for the given term with the lowest p value (default = `FALSE`)
`...`	additional arguments for `active_snw_enrichment_wrapper`

Details

This function takes in a data frame consisting of Gene Symbol, log-fold-change and adjusted-p values. After input testing, any gene symbols that are not in the PIN are converted to alias symbols if the alias is in the PIN. Next, active subnetwork search is performed. Enrichment analysis is performed using the genes in each of the active subnetworks. Terms with adjusted-p values lower than enrichment_threshold are discarded. The lowest adjusted-p value (over all subnetworks) for each term is kept. This process of active subnetwork search and enrichment is repeated for a selected number of iterations, which is done in parallel. Over all iterations, the lowest and the highest adjusted-p values, as well as number of occurrences are reported for each enriched term.

Value

Data frame of pathfindR enrichment results. Columns are:

ID: ID of the enriched term
Term_Description: Description of the enriched term
Fold_Enrichment: Fold enrichment value for the enriched term (Calculated using ONLY the input genes)
occurrence: the number of iterations that the given term was found to enriched over all iterations
support: the median support (proportion of active subnetworks leading to enrichment within an iteration) over all iterations
lowest_p: the lowest adjusted-p value of the given term over all iterations
highest_p: the highest adjusted-p value of the given term over all iterations
non_Signif_Snw_Genes (OPTIONAL): the non-significant active subnetwork genes, comma-separated
Up_regulated: the up-regulated genes (as determined by ‘change value' > 0, if the 'change column' was provided) in the input involved in the given term’s gene set, comma-separated. If change column not provided, all affected are listed here.
Down_regulated: the down-regulated genes (as determined by ‘change value' < 0, if the 'change column' was provided) in the input involved in the given term’s gene set, comma-separated

The function also creates an HTML report with the pathfindR enrichment results linked to the visualizations of the enriched terms in addition to the table of converted gene symbols. This report can be found in 'output_dir/results.html' under the current working directory.

By default, a bubble chart of top 10 enrichment results are plotted. The x-axis corresponds to fold enrichment values while the y-axis indicates the enriched terms. Sizes of the bubbles indicate the number of significant genes in the given terms. Color indicates the -log10(lowest-p) value; the more red it is, the more significant the enriched term is. See enrichment_chart.

Warning

Especially depending on the protein interaction network, the algorithm and the number of iterations you choose, 'active subnetwork search + enrichment' component of run_pathfindR may take a long time to finish.

Examples

## Not run: 
run_pathfindR(example_pathfindR_input)

## End(Not run)

[Package pathfindR version 2.4.1 Index]