get_driver_genes: Get genes driving significant 'MAGMA_celltyping' results

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

Get genes driving significant MAGMA_celltyping results

Description

Infers the genes driving significant cell-type-specific enrichment results by computing the mean rank of the adjusted Z-score from the GWAS gene annotation file ("ADJ_ZSTAT") and the cell-type specificity score from the CellTypeDataset ("specificity_proportion").

Usage

get_driver_genes(
  ctd,
  ctd_species = infer_ctd_species(ctd = ctd),
  prepare_ctd = TRUE,
  magma_res,
  GenesOut_dir,
  fdr_thresh = 0.05,
  n_genes = 100,
  spec_deciles = NULL,
  verbose = TRUE,
  ...
)

Arguments

ctd	CellTypeData object
ctd_species	Either 'human' or 'mouse'
prepare_ctd	Whether to run prepare_quantile_groups on the ctd first.
magma_res	Merged results from merge_results.
GenesOut_dir	Folder to search for .genes.out files implicated in magma_res.
fdr_thresh	FDR threshold for magma_res.
n_genes	Max number of drive genes to return per cell-type enrichment.
spec_deciles	[Optional] Which "specificity_proportion" deciles to include when calculating driver genes. (10 = most specific).
verbose	Print messages.
...	Arguments passed on to EWCE::standardise_ctd dataset CellTypeData. name. input_species Which species the gene names in exp come from. See list_species for all available species. output_species Which species' genes names to convert exp to. See list_species for all available species. sctSpecies_origin Species that the sct_data originally came from, regardless of its current gene format (e.g. it was previously converted from mouse to human gene orthologs). This is used for computing an appropriate backgrund. non121_strategy How to handle genes that don't have 1:1 mappings between input_species:output_species. Options include: "drop_both_species" or "dbs" or 1 : Drop genes that have duplicate mappings in either the input_species or output_species (DEFAULT). "drop_input_species" or "dis" or 2 : Only drop genes that have duplicate mappings in the input_species. "drop_output_species" or "dos" or 3 : Only drop genes that have duplicate mappings in the output_species. "keep_both_species" or "kbs" or 4 : Keep all genes regardless of whether they have duplicate mappings in either species. "keep_popular" or "kp" or 5 : Return only the most "popular" interspecies ortholog mappings. This procedure tends to yield a greater number of returned genes but at the cost of many of them not being true biological 1:1 orthologs. "sum","mean","median","min" or "max" : When gene_df is a matrix and gene_output="rownames", these options will aggregate many-to-one gene mappings (input_species-to-output_species) after dropping any duplicate genes in the output_species. method R package to use for gene mapping: "gprofiler" : Slower but more species and genes. "homologene" : Faster but fewer species and genes. "babelgene" : Faster but fewer species and genes. Also gives consensus scores for each gene mapping based on a several different data sources. force_new_quantiles By default, quantile computation is skipped if they have already been computed. Set =TRUE to override this and generate new quantiles. force_standardise If ctd has already been standardised, whether to rerun standardisation anyway (Default: FALSE). remove_unlabeled_clusters Remove any samples that have numeric column names. numberOfBins Number of non-zero quantile bins. keep_annot Keep the column annotation data if provided. keep_plots Keep the dendrograms if provided. as_sparse Convert to sparse matrix. as_DelayedArray Convert to DelayedArray. rename_columns Remove replace_chars from column names. make_columns_unique Rename each columns with the prefix dataset.species.celltype.

Examples

ctd <- ewceData::ctd()
GenesOut_dir <- MAGMA.Celltyping::import_magma_files()
magma_res <- MAGMA.Celltyping::merge_results(
    MAGMA.Celltyping::enrichment_results)
genesets <- MAGMA.Celltyping::get_driver_genes(ctd = ctd, 
                                               magma_res = magma_res, 
                                               GenesOut_dir = GenesOut_dir, 
                                               fdr_thresh = 1)

NathanSkene/MAGMA_Celltyping documentation built on March 5, 2025, 5:44 a.m.