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Parallel differential expression for single-cell perturbation sequencing

Project description

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
reference str "non-targeting" Reference group name (modes: ref, on_target)
gene_col str Column mapping groups to target genes (mode: on_target)

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 log2(target_mean / ref_mean)
percent_change (target_mean - ref_mean) / ref_mean
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.

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