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A COMPOSITIONAL MODEL TO ASSESS EXPRESSION CHANGES FROM SINGLE-CELL RNA-SEQ DATA.

Xiuyu Ma1, Keegan Korthauer2, Christina Kendziorski3

  • 1Department of Statistics, University of Wisconsin-Madison.

The Annals of Applied Statistics
|June 19, 2023
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Summary
This summary is machine-generated.

This study introduces an empirical Bayesian mixture model to detect changes in single-cell gene expression distributions. The novel approach improves sensitivity by integrating cell subtype information for more accurate gene scoring.

Keywords:
Local false discovery rateclusteringdouble Dirichlet mixtureempirical Bayesmixture model

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Area of Science:

  • Computational Biology
  • Genomics
  • Biostatistics

Background:

  • Accurately scoring genes for expression changes in single-cell data is challenging.
  • Existing methods may not fully leverage cell-subtype heterogeneity.
  • Detecting subtle shifts in gene expression distributions requires robust statistical approaches.

Purpose of the Study:

  • To develop and evaluate a novel empirical Bayesian mixture approach for scoring gene expression changes.
  • To enhance the detection of differential gene expression distributions by incorporating cell-subtype information.
  • To improve sensitivity in identifying genes with altered expression patterns across cellular conditions.

Main Methods:

  • An empirical Bayesian mixture model was developed.
  • Cell subtype structure from cluster analysis was leveraged.
  • A prior distribution over multinomial probability vectors was constructed.
  • Posterior probabilities for gene distribution changes were derived.

Main Results:

  • The proposed approach demonstrated improved sensitivity in numerical experiments.
  • Integration of cell clustering enhanced gene-level information on expression changes.
  • The model allows for gene-specific mixtures over subtypes.
  • Novel information sharing between cell clustering and gene scoring was achieved.

Conclusions:

  • The empirical Bayesian mixture approach offers a sensitive method for detecting differential gene expression distributions.
  • Leveraging cell-subtype structure significantly boosts the power of gene-level analysis.
  • This method provides a robust framework for analyzing single-cell expression data.