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Updated: Jun 29, 2025

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PMF-GRN: a variational inference approach to single-cell gene regulatory network inference using probabilistic matrix

Claudia Skok Gibbs1, Omar Mahmood1, Richard Bonneau1,2,3

  • 1Center for Data Science, New York University, New York, NY, 10011, USA.

Genome Biology
|April 8, 2024
PubMed
Summary

We developed Probabilistic Matrix Factorization for Gene Regulatory Network Inference (PMF-GRN) to improve gene regulatory network inference from single-cell data. Our method provides more accurate GRN reconstruction and uncertainty estimates compared to existing approaches.

Keywords:
Gene expressionGene regulatory network inferenceProbabilistic matrix factorizationSingle cellVariational inference

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Area of Science:

  • Computational Biology
  • Genomics
  • Systems Biology

Background:

  • Inferring gene regulatory networks (GRNs) from single-cell data is crucial for understanding cellular processes.
  • Current methods face limitations in accuracy and lack robust uncertainty quantification.

Purpose of the Study:

  • To introduce Probabilistic Matrix Factorization for Gene Regulatory Network Inference (PMF-GRN).
  • To address the challenges of accuracy and uncertainty estimation in single-cell GRN inference.

Main Methods:

  • Utilized single-cell expression data to infer latent factors representing transcription factor activity and regulatory relationships.
  • Employed variational inference for hyperparameter optimization and model comparison.
  • Benchmarked PMF-GRN against state-of-the-art methods using both synthetic and real single-cell datasets.

Main Results:

  • PMF-GRN demonstrates superior accuracy in inferring gene regulatory networks compared to existing methods.
  • The method provides well-calibrated estimates of uncertainty for the inferred regulatory relationships.
  • Successful application on real single-cell datasets validates its practical utility.

Conclusions:

  • PMF-GRN offers a significant advancement in the field of single-cell GRN inference.
  • The incorporation of uncertainty estimation enhances the reliability and interpretability of inferred networks.
  • This probabilistic approach facilitates principled model selection and comparison in GRN analysis.