calculate_conditional_geneset_enrichment: Use MAGMA to test enrichment in a geneset

In NathanSkene/MAGMA_Celltyping: Find Causal Cell-Types Underlying Complex Trait Genetics

Use MAGMA to test enrichment in a geneset

Description

Run gene set enrichment analysis with a given geneset on a GWAS previously mapped to genes (using map_snps_to_genes), while conditioning on a given cell-type or list of cell-types (controlledCTs), as defined by the "specificity_quantiles" matrix in a given level (controlledAnnotLevel) of the provide CellTypeDataset (ctd). This allows one to conduct gene set enrichment analyses while controlling for strong cell-type-specific signatures.

Usage

calculate_conditional_geneset_enrichment(
  geneset,
  ctd,
  ctd_species = infer_ctd_species(ctd),
  controlledAnnotLevel = 1,
  controlledCTs,
  prepare_ctd = TRUE,
  gwas_sumstats_path = NULL,
  magma_dir = NULL,
  analysis_name = "MainRun",
  upstream_kb = 35,
  downstream_kb = 10,
  geneset_species = infer_geneset_species(geneset),
  version = NULL,
  verbose = TRUE
)

Arguments

geneset	Genes which are to be tested. Can be gene symbols (or other gene IDs) from any species listed in list_species.
ctd	Cell type data structure containing specificity_quantiles.
ctd_species	Species name relevant to the CellTypeDataset (ctd). See list_species for all available species. If ctd_species=NULL (default), the ctd species will automatically be inferred using infer_species.
controlledAnnotLevel	Annotation level of the celltypes being controlled for.
controlledCTs	Array of the celltype to be controlled for, e.g. c("Interneuron type 16","Medium Spiny Neuron).
prepare_ctd	Whether to run prepare_quantile_groups on the ctd first.
gwas_sumstats_path	File path of the summary statistics file.
magma_dir	Path to folder containing the pre-computed MAGMA GWAS files (.gsa.rawand .gsa.out).
analysis_name	Used in file names which area created.
upstream_kb	How many kb upstream of the gene should SNPs be included?
downstream_kb	How many kb downstream of the gene should SNPs be included?
geneset_species	Species that the geneset came from. Can be any species listed in list_species. If geneset_species!="human", the geneset will be converted to 1:1 human orthologs using convert_orthologs.
version	MAGMA version to use.
verbose	Print messages.

Value

data.table of baseline (column name prefix "BASELINE_") and conditioned (column name prefix "COND_") gene set enrichment results.

Examples

#### Import data ####
ctd <- MAGMA.Celltyping::get_ctd("ctd_allKI")
magma_dir <- MAGMA.Celltyping::import_magma_files(ids = "ieu-a-298")
geneset <- MAGMA.Celltyping::rbfox_binding

res <- MAGMA.Celltyping::calculate_conditional_geneset_enrichment(
    geneset = geneset,
    ctd = ctd,
    controlledAnnotLevel = 1,
    controlledCTs = "pyramidal SS",
    magma_dir = magma_dir,
    analysis_name = "Rbfox_16_pyrSS",  
    geneset_species = "mouse", 
    ctd_species = "mouse") 

NathanSkene/MAGMA_Celltyping documentation built on Oct. 11, 2024, 7:19 a.m.