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DSGE: Disruption Score of Gene Expression

Gene set-level transcriptional perturbation analysis. Converts differential expression p-values into per-gene z-scores and tests whether each gene set shows stronger perturbation than expected under a size-matched permutation null. Uses GPD tail extrapolation for extreme-value p-values.

Installation

# install.packages("devtools")
devtools::install_github("LHJLab/DSGE")

Quick Start

library(DSGE)
library(org.Hs.eg.db)

# Build pathway-gene map from Bioconductor OrgDb
pw <- get_pathway_genes_db(org.Hs.eg.db, min_size = 10)

# Read DE results (any tool — DESeq2, edgeR, limma, Seurat, etc.)
res <- read.csv("your_de_results.csv")
# Required columns: pvalue, gene symbol
# Optional: baseMean/AveExpr (for expression filtering), log2FoldChange (for direction)

# Run pathway analysis
result <- pathway_dsge(pw, pvalue = res$pvalue, base_mean = res$AveExpr,
                        gene_names = res$gene, gene_id_col = "db_object_symbol",
                        n_perm = 100000, n_cores = 4,
                        directional = TRUE, direction_vec = res$log2FoldChange,
                        return_null = TRUE)

# Significant pathways
head(result$table[result$table$p_adj < 0.05, c("go_id", "go_name", "dsge_std", "p_adj")])

# Plot null distribution for selected pathways
plot_dsge(result, go_ids = c("GO:0007264", "GO:0018108"))

Key parameters: min_size, max_size, n_perm, use_gpd, directional (with direction_vec), nds_top_frac , n_cores.

Documentation

For detailed documentation with worked examples, parameter references, and diagnostic plots, see the DSGE Wiki.

License

MIT