Transcript-Type Aware Gene Set Enrichment

Runs gene set enrichment analysis (fgsea::fgseaMultilevel()) separately for transcripts of each type, ranking transcripts by log2 fold-change. Gene sets defined on gene symbols are expanded to all transcripts of their genes, so each transcript category (protein coding, retained intron, nonsense-mediated decay, ...) is tested on its own and in the combined "unproductive" category.

The IsoformicExperiment method uses the stored transcript-level results and the annotation; the data frame method takes a transcript table with transcript_name, transcript_type and log2FC columns plus a tx_to_gene table.

read_gmt() reads gene sets in GMT format into a named list, and plot_enrichment() draws a dot plot of enrichment results.

Usage

run_enrichment(
  self,
  genesets_list,
  tx_to_gene = NULL,
  pval_cutoff = 0.05,
  tx_types = NULL,
  min_size = 15,
  max_size = 500,
  ...
)

default_enrichment_types(annotation_types = NULL)

read_gmt(path)

plot_enrichment(
  enrichment_df,
  n = 30,
  experiments = NULL,
  nes_cutoff = 0,
  strip_prefix = "^[A-Z]+_",
  label_width = 50
)

Arguments

self: An IsoformicExperiment or a transcript-level DE table.
genesets_list: Named list of character vectors (gene symbols), as returned by read_gmt().
tx_to_gene: Data frame with transcript_name and gene_name columns; required by the data frame method, ignored otherwise.
pval_cutoff: Keep pathways with pval at or below this value; NULL keeps all.
tx_types: Named list defining the transcript categories to test. Defaults to default_enrichment_types(), which picks processed_transcript or protein_coding_CDS_not_defined depending on the annotation version.
min_size, max_size: Minimum and maximum gene set size passed to fgsea.
...: Passed on to fgsea::fgseaMultilevel().
annotation_types: Transcript types present in the annotation, used to choose between processed_transcript and protein_coding_CDS_not_defined.
path: Path to a GMT file.
enrichment_df: Result of run_enrichment().
n: Number of top pathways (by adjusted p-value) to show.
experiments: Categories to show; NULL shows all.
nes_cutoff: Minimum absolute NES to show.
strip_prefix: Regular expression removed from pathway names before plotting (default drops MSigDB collection prefixes such as REACTOME_).
label_width: Pathway labels are wrapped to this many characters.

Value

run_enrichment() returns a tibble with the fgsea columns plus experiment (the transcript category). read_gmt() returns a named list. plot_enrichment() returns a ggplot object.

Examples

iso <- example_isoformic()
gmt <- system.file("extdata", "reactome_subset.gmt", package = "isoformic")
genesets <- read_gmt(gmt)
length(genesets)
#> [1] 40

if (requireNamespace("fgsea", quietly = TRUE)) {
  res <- run_enrichment(iso, genesets, pval_cutoff = NULL, min_size = 2)
  head(res)
  plot_enrichment(res, n = 10)
}