pdex

Parallel differential expression for single-cell perturbation sequencing.

Installation

# add to pyproject.toml
uv add pdex

# add to env
uv pip install pdex

Overview

pdex computes per-gene differential expression statistics between perturbation groups in single-cell data using Mann-Whitney U tests with FDR correction. It was originally designed for CRISPR screen and perturbation sequencing datasets with many groups and large cell counts.

It supports dense and sparse (CSR) expression matrices, and uses numba-mwu for Numba-accelerated Mann-Whitney U computation.

Modes

Mode	Description
"ref"	Each group vs a single reference group (default: "non-targeting")
"all"	Each group vs all remaining cells (1-vs-rest)
"on_target"	Each group vs the reference at its single target gene only

Usage

Reference mode (default)

import anndata as ad
from pdex import pdex

adata = ad.read_h5ad("screen.h5ad")

results = pdex(
    adata,
    groupby="guide",
    mode="ref",
    is_log1p=False,
)

1-vs-rest mode

results = pdex(
    adata,
    groupby="guide",
    mode="all",
    is_log1p=False,
)

On-target mode

Requires a column in adata.obs mapping each group to its target gene:

results = pdex(
    adata,
    groupby="guide",
    mode="on_target",
    gene_col="target_gene",
    is_log1p=False,
)

Parameters

Parameter	Type	Default	Description
adata	AnnData	required	Annotated data matrix (dense or sparse CSR)
groupby	str	required	Column in adata.obs defining groups
mode	str	"ref"	Comparison mode: "ref", "all", or "on_target"
threads	int	0	Numba thread count (0 = all CPUs)
is_log1p	bool | None	None	Whether data is log1p-transformed. Auto-detected if None
geometric_mean	bool	True	Use geometric mean for pseudobulk (vs arithmetic)
as_pandas	bool	False	Return a pandas DataFrame instead of Polars
epsilon	float	1e-9	Pseudocount used for log2_fold_change and percent_change; pass 0.0 for legacy one-sided ±inf values
cpm_filter	float | None	None	Optional pooled-CPM floor filter; drops rows where both target and reference CPM are at or below the threshold
reference	str	"non-targeting"	Reference group name (modes: ref, on_target)
gene_col	str	—	Column mapping groups to target genes (mode: on_target)

CPM filter

cpm_filter is an opt-in floor filter. When set to a threshold T, a (target, feature) row is dropped only when the gene's pooled CPM is <= T in both the target group and the reference group. Rows are kept when either side has CPM > T.

The CPM view is used only for filtering: reported means, fold changes, MWU statistics, and p-values are still computed from the original expression scale. When is_log1p=True, counts are recovered with expm1 before CPM is computed. FDR is corrected over the surviving genes only.

Output

Returns a Polars DataFrame (or pandas if as_pandas=True) with one row per (group, gene) pair:

Column	Description
target	Perturbation group name
feature	Gene name
target_mean	Pseudobulk mean for the target group (count space)
ref_mean	Pseudobulk mean for the reference (count space)
target_membership	Number of cells in the target group
ref_membership	Number of cells in the reference
fold_change	Deprecated alias for log2_fold_change (identical values). Will be removed in pdex 0.3.0.
log2_fold_change	log2((target_mean + epsilon) / (ref_mean + epsilon)). With default epsilon=1e-9, one-sided zeros are large finite values; with epsilon=0.0, one-sided zeros yield ±inf. Genes unexpressed in both groups (0/0) report 0.0, not NaN.
percent_change	(target_mean - ref_mean) / (ref_mean + epsilon). With default epsilon=1e-9, zero-reference cases are finite; with epsilon=0.0, a zero reference with nonzero target yields +inf. Genes unexpressed in both groups (0/0) report 0.0, not NaN.
p_value	Mann-Whitney U p-value
statistic	Mann-Whitney U statistic
fdr	FDR-corrected p-value (per-group, across genes). For on_target mode, this is applied across all groups. When cpm_filter is set, FDR is corrected over surviving genes only.