scFastDE

Fast Donor-Weighted Pseudo-Bulk Differential Expression for scRNA-seq

Bioconductor version: 3.24 · Package version: 0.99.3

scFastDE provides fast, donor-weighted pseudo-bulk differential expression analysis for multi-donor single-cell RNA-seq experiments. Unlike existing tools that loop over genes serially, scFastDE uses vectorised sparse matrix operations across all genes simultaneously, achieving 10-50x speed gains on large datasets. Donors are weighted by the square root of their cell count, giving principled influence to well-represented donors without discarding donors with few cells. Paired experimental designs (same donors in multiple conditions) are automatically detected; pseudo-bulk is then aggregated per donor-condition pair and a blocking model accounts for inter-donor variation. A sparse pseudo-bulk guard automatically handles cell types where some donors fall below a minimum cell threshold. All functions operate natively on SingleCellExperiment objects.

if (!require("BiocManager", quietly = TRUE))
    install.packages("BiocManager")

BiocManager::install("scFastDE")