controlled_geneset_enrichment {EWCE}

R Documentation

Celltype controlled geneset enrichment

Description

controlled_geneset_enrichment tests whether a functional geneset is still enriched in a disease gene set after controlling for the disease geneset's enrichment in a particular cell type (the 'controlledCT')

Usage

controlled_geneset_enrichment(
  disease_genes,
  functional_genes,
  bg_genes,
  sct_data,
  annotLevel,
  reps,
  controlledCT
)

Arguments

disease_genes	Array of gene symbols containing the disease gene list. Does not have to be disease genes. Must be from same species as the single cell transcriptome dataset.
functional_genes	Array of gene symbols containing the functional gene list. The enrichment of this geneset within the disease_genes is tested. Must be from same species as the single cell transcriptome dataset.
bg_genes	Array of gene symbols containing the background gene list.
sct_data	List generated using generate_celltype_data
annotLevel	an integer indicating which level of the annotation to analyse. Default = 1.
reps	Number of random gene lists to generate (default=100 but should be over 10000 for publication quality results)
controlledCT	(optional) If not NULL, and instead is the name of a cell type, then the bootstrapping controls for expression within that cell type

Value

A list containing three data frames:

• p_controlled The probability that functional_genes are enriched in disease_genes while controlling for the level of specificity in controlledCT

• z_controlled The z-score that functional_genes are enriched in disease_genes while controlling for the level of specificity in controlledCT

• p_uncontrolled The probability that functional_genes are enriched in disease_genes WITHOUT controlling for the level of specificity in controlledCT

• z_uncontrolled The z-score that functional_genes are enriched in disease_genes WITHOUT controlling for the level of specificity in controlledCT

• reps=reps

• controlledCT

• actualOverlap=actual The number of genes that overlap between functional and disease gene sets

Examples

library(ewceData)
# See the vignette for more detailed explanations
# Gene set enrichment analysis controlling for cell type expression
# set seed for bootstrap reproducibility
set.seed(12345678)
ctd <- ctd()
mouse_to_human_homologs <- mouse_to_human_homologs()
m2h = unique(mouse_to_human_homologs[,c("HGNC.symbol","MGI.symbol")])
schiz_genes <- schiz_genes()
id_genes <- id_genes()
mouse.hits.schiz = unique(m2h[m2h$HGNC.symbol %in% schiz_genes,"MGI.symbol"])
mouse.bg  = unique(m2h$MGI.symbol)
hpsd_genes <- hpsd_genes()
mouse.hpsd = unique(m2h[m2h$HGNC.symbol %in% hpsd_genes,"MGI.symbol"])
# Use 3 bootstrap lists for speed, for publishable analysis use >10000
reps=3
res_hpsd_schiz =
    controlled_geneset_enrichment(disease_genes=mouse.hits.schiz,
                                    functional_genes = mouse.hpsd,
                                    bg_genes = mouse.bg,
                                    sct_data = ctd, annotLevel = 1,
                                    reps=reps,
                                    controlledCT="pyramidal CA1")

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