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Calculates statistical significance for gene-pathway associations using the GeneWalk algorithm. For each gene-pathway pair, this function computes p-values and FDR corrections (both globally across all pairs and per-gene) across multiple network permutations. The final output includes mean values and 95% confidence intervals for all statistics.

The function processes all permutations in Rust for optimal performance, calculating cosine similarities between gene and pathway embeddings, determining p-values based on null distributions from randomised networks, and applying Benjamini-Hochberg FDR corrections.

Usage

calculate_genewalk_stats(object, .verbose = TRUE)

Arguments

object

The GeneWalk object containing actual and permuted embeddings. See GeneWalk().

.verbose

Logical. If TRUE, prints progress messages during calculation. Default is TRUE.

Value

The input object with an added stats property containing a data.table with the following columns for each gene-pathway pair:

  • gene - Gene identifier

  • pathway - Pathway identifier

  • avg_pval - Mean p-value across permutations

  • pval_ci_lower, pval_ci_upper - 95% CI for p-values

  • avg_global_fdr - Mean global FDR across permutations

  • global_fdr_ci_lower,global_fdr_ci_upper - 95% CI for global FDR

  • avg_gene_fdr - Mean gene-wise FDR across permutations

  • gene_fdr_ci_lower,gene_fdr_ci_upper - 95% CI for gene-wise FDR

References

Ietswaart, et al., Genome Biol, 2021