Over-Representation Analysis (ORA)

Fast over-representation analysis.

Usage

run_ORA(
  input,
  background,
  database = names(MotrpacHumanPreSuspensionAnalysis::MOLECULAR_SIGNATURES),
  path_to_gmt = NULL,
  min_size = 5L,
  overlap_cutoff = 0.7
)

Arguments

input: character; vector of "interesting" features. Most likely genes, but may be RefMet metabolite IDs or singly-phosphorylated peptides.
background: character; vector of all features that were analyzed. Used to filter the molecular signatures.
database: character; one or more names specifying the database(s) to test. Options are (case insensitive) "BIOCARTA", "KEGG_MEDICUS", "PID", "REACTOME", "WP" (WikiPathways database), "GOBP", "GOCC", "GOMF", "MITOCARTA" (MitoCarta3.0 database), "PSP" (PhosphoSitePlus kinases; only valid when selected_omes contains "prot-ph"), or "REFMET" (RefMet chemical subclasses; only valid when selected_omes contains "metab"). See MOLECULAR_SIGNATURES for details.
path_to_gmt: character; (optional) path to one or more GMT files. Passed to TMSig::readGMT. If provided, database is ignored.
min_size: integer; the minimum set size for testing.
overlap_cutoff: numeric; the minimum proportion of genes in each set that must appear in a given dataset. Used to pre-filter sets. Does not affect "metab" or "prot-ph" results. This will always be 0.1 for "prot-ol" results.

Value

An object of class data.frame with the following columns:

collection: factor; the broad molecular signature collection. Only included when path_to_gmt is NULL. See SET_TO_ID for details.
database: factor; the molecular signature database. Only included when path_to_gmt is NULL. See SET_TO_ID for details.
set_id: character; a unique ID for the molecular signature. Only included when path_to_gmt is NULL. See SET_TO_ID for details.
set: character; the molecular signature being tested. For global proteomics and transcriptomics, these are gene sets. For phosphoproteomics, these are kinase sets.
set_short: character; a shortened version of set. Only included when path_to_gmt is NULL. See SET_TO_ID for details.
set_size: integer; the number of molecules in the set that were present in the background vector.
set_size_DB: integer; the number of molecules in the set, as defined in MOLECULAR_SIGNATURES.
size_ratio: numeric; the ratio of set_size to set_size_DB, rounded to the nearest thousandth. A measure of confidence that the gene set being tested is correctly described by the entry in the set column. While smaller values do not necessarily indicate that the results are unreliable, terms from the gene set databases should be treated with caution.
set_size_in_input: integer; the number of molecules in the set that were present in the input vector.
input_size: integer; the size of the input vector.
background_size: integer; the size of the background vector.
p_value: numeric; the two-sided p-value.
adj_p_value: numeric; the BH-adjusted p-value. P-values are adjusted within each combination of tissue, assay, contrast, and collection.

Examples

# Use genes from all gene sets as the background
bg <- MotrpacHumanPreSuspensionAnalysis::MOLECULAR_SIGNATURES
bg[c("PSP", "REFMET")] <- NULL
bg <- unique(unlist(bg))

# Use all genes from the MitoCarta OXPHOS term as the interesting subset
input <- MotrpacHumanPreSuspensionAnalysis::MOLECULAR_SIGNATURES$MITOCARTA[["MITOCARTA_OXPHOS"]]

res <- run_ORA(input = input, background = bg)
#> Loading required package: limma
head(res)
#>   collection  database set_id
#> 1  MITOCARTA MITOCARTA  11461
#> 2         C2  REACTOME  13334
#> 3  MITOCARTA MITOCARTA  11463
#> 4         C2  REACTOME  13668
#> 5         C5      GOCC  08593
#> 6         C2        WP  14188
#>                                                                                                                         set
#> 1                                                                                                          MITOCARTA_OXPHOS
#> 2 REACTOME_RESPIRATORY_ELECTRON_TRANSPORT_ATP_SYNTHESIS_BY_CHEMIOSMOTIC_COUPLING_AND_HEAT_PRODUCTION_BY_UNCOUPLING_PROTEINS
#> 3                                                                                                 MITOCARTA_OXPHOS subunits
#> 4                                                     REACTOME_THE_CITRIC_ACID_TCA_CYCLE_AND_RESPIRATORY_ELECTRON_TRANSPORT
#> 5                                                                                             GOCC_ORGANELLE_INNER_MEMBRANE
#> 6                                                                 WP_ELECTRON_TRANSPORT_CHAIN_OXPHOS_SYSTEM_IN_MITOCHONDRIA
#>                                                      set_short set_size
#> 1                                                       OXPHOS      169
#> 2        REACTOME_RESPIRATORY_ELECTRON_TRANSPORT_ATP...(13334)      127
#> 3                                              OXPHOS subunits      102
#> 4 REACTOME_THE_CITRIC_ACID_TCA_CYCLE_AND_RESPIRATORY...(13668)      178
#> 5                                GOCC_ORGANELLE_INNER_MEMBRANE      553
#> 6    WP_ELECTRON_TRANSPORT_CHAIN_OXPHOS_SYSTEM_IN_MITOCHONDRIA      105
#>   set_size_DB size_ratio set_size_in_input input_size background_size
#> 1         169          1               169        169           40385
#> 2         127          1               114        169           40385
#> 3         102          1               102        169           40385
#> 4         178          1               114        169           40385
#> 5         553          1               140        169           40385
#> 6         105          1                97        169           40385
#>         p_value   adj_p_value
#> 1  0.000000e+00  0.000000e+00
#> 2 5.734173e-277 9.920120e-275
#> 3 1.947040e-260 3.699375e-259
#> 4 5.434940e-245 4.701223e-243
#> 5 1.825406e-237 1.522389e-234
#> 6 3.382743e-235 1.950715e-233

Usage

Arguments

Value

See also

Examples