Wrapper function for Bootstrap Over-Representation Analysis (ORA)

This function performs a bootstrap-based over-representation analysis (ORA) on a given list of metabolites and background.

Usage

Run_bootstrap_ORA(
  marker_list,
  background,
  custom_universe = NULL,
  alpha_cutoff = 0.05,
  min_intersection = 3,
  consider_isobars = T,
  polarization_mode = NA,
  mass_range_ppm = 3,
  annot_db = "HMDB",
  annot_custom_db = NULL,
  use_LION = F,
  endogenous_only = T,
  pathway_assoc_only = F,
  remove_expected_predicted = T,
  annot_list = NULL,
  annot_weights = NULL,
  n_bootstraps = 50,
  boot_fract_cutoff = 0.5,
  q.val_cutoff = 0.2,
  selected_terms = NULL,
  adjust_contingency = T,
  report_ambiguity_scores = F
)

Arguments

marker_list: A vector or list of marker sets to analyze.
background: A list of named terms where each term is a character vector of metabolites.
custom_universe: An optional vector specifying a custom universe of terms. If not provided all metabolites in background will be used as universe.
alpha_cutoff: A numeric value indicating the alpha cutoff for significance.
min_intersection: An integer specifying the minimum intersection required between input list and a given term in background.
consider_isobars: A logical indicating whether to consider isobars.
polarization_mode: A parameter for polarization mode. If provided, it will be used to consider isomers and isobars.
mass_range_ppm: A numeric value for mass range in parts per million (ppm).
annot_db: A character string specifying the annotation database(s) used for annotation. Check build_iso_bg for more information.
annot_custom_db: An optional custom annotation database. If provided, it will be used alongside or instead of the specified annotation database.
use_LION: A logical indicating whether to use LION ontology for select isomers/isobars for background.
endogenous_only: A logical indicating whether to consider only endogenous compounds. Applies only for HMDB and CoreMetabolome annotation databases.
pathway_assoc_only: A logical indicating whether to consider only pathway-associated compounds. Applies only for HMDB and CoreMetabolome annotation databases.
remove_expected_predicted: A logical indicating whether to remove expected and predicted annotations. Applies only for HMDB and CoreMetabolome annotation databases.
annot_list: An optional list of annotations. If provided, it will be used instead of generating isomers from built-in formula to molecule mapping.
annot_weights: An optional list of annotation weights. If provided, it will be used in the ambiguity score calculation and bootstrap analysis.
n_bootstraps: An integer specifying the number of bootstrap iterations.
boot_fract_cutoff: A numeric value specifying the minimum bootstrap fraction cutoff required. Default to 0.5 .
q.val_cutoff: A numeric value specifying the q-value cutoff for significance.
selected_terms: An optional vector of selected terms to focus on. If provided, the analysis will be restricted to these terms.
adjust_contingency: A logical indicating whether to adjust the contingency table to account for isomeric ambiguity.
report_ambiguity_scores: A logical indicating whether to report ambiguity scores. If TRUE, ambiguity scores will be included in the results.

Value

A list containing the ORA results for each group of markers. Both filtered and per-bootstrap results are provided.

Examples

if (FALSE) { # \dontrun{
data("example_ORA_markers")
data("example_ORA_obj")
object = example_ORA_obj
enrich_res <- Run_bootstrap_ORA(
  marker_list = example_ORA_markers,
  background = object$pathway_list,
  polarization_mode = object$polarization_mode,
  mass_range_ppm = object$mass_range_ppm,
  annot_db = object$Annotation_database,
  annot_custom_db = object$Custom_database,
  use_LION = ifelse(stringr::str_detect(object$background_name, "LION"), TRUE, FALSE),
  endogenous_only = object$endogenous_only,
  pathway_assoc_only = object$pathway_assoc_only,
  remove_expected_predicted = object$remove_expected_predicted,
  annot_weights = object$annotation.weights,
  consider_isobars = object$consider_isobars,
  annot_list = object$annotations
)
} # }