HALRA

HALRA (High-performance ALRA) is a Python implementation of the ALRA algorithm for imputing missing values in single-cell RNA-seq data [1]. It is designed to operate efficiently on sparse matrices and scale to large datasets by preserving sparsity throughout the pipeline wherever possible.

HALRA performs:

• Low-rank matrix reconstruction via randomized SVD
• Gene-wise thresholding of reconstructed values
• Per-gene rescaling to match observed statistics
• Restoration of observed (nonzero) values

The goal is to denoise and impute dropout values while preserving biological signal.

Expected Input

HALRA supports two input types:

1. AnnData

• .X should contain a dense NumPy array or a SciPy sparse matrix (CSR/CSC)
• .obs_names and .var_names are used as cell and gene labels

2. Raw matrix + labels

• matrix: NumPy ndarray or SciPy sparse matrix (cell x gene)
• cells: list/array of cell names (length = n_rows)
• genes: list/array of gene names (length = n_cols)

HALRA requires log-normalized count data, so either log normalize your data first or pass normalize=True to the halra function when imputing.

Installation

HALRA can be installed as a pip package but requires Python >= 3.10. Example:

conda create -n halra_env python=3.10
conda activate halra_env
pip install halra

Usage Example (AnnData)

import anndata as ad
from halra import halra

# Load your AnnData object
adata = ad.read_h5ad("anndata.h5ad")

# Run HALRA (this assumes .X is not already normalized)
adata_imputed = halra(adata, normalize=True)

# Result:
# adata_imputed.X now contains imputed values
# All metadata (.obs, .var, etc.) is preserved (filtered if needed)

Usage Example (10x)

import os
import pandas as pd
from scipy.io import mmread
from halra import halra

# Load 10x files
mtx_dir = "/path/to/dir"
matrix = mmread(os.path.join(mtx_dir, "matrix.mtx")).T
features = pd.read_csv(os.path.join(mtx_dir, "features.tsv"), sep="\t", header=None, usecols=[0])
barcodes = pd.read_csv(os.path.join(mtx_dir, "barcodes.tsv"), sep="\t", header=None)

# Run HALRA
imputed_matrix, cells, genes = halra(matrix, barcodes, features, normalize=True)

# Result:
# imputed_matrix contains imputed values
# cells and genes contain the filtered cell/gene labels

Dependency Notes

HALRA depends on:

• numpy
• scipy
• scikit-learn (for randomized SVD)
• anndata (>=0.10)

Current Limitations and Experimental Features

• Reconstruction step is dense (SVD-based), which may limit scalability for extremely large datasets (>1M cells)
• Distributed and HPC-oriented implementations of HALRA are under active development and can be found in the experimental/ directory. These are not yet part of the stable package API.

References

[1] Linderman, G. C. et al. Zero-preserving imputation of single-cell RNA-seq data. Nat Commun 13, (2022).

License

This project is licensed under the MIT License - see the LICENSE file for details.