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scDC: single cell differential composition analysis.

Yue Cao1, Yingxin Lin1, John T Ormerod1

  • 1School of Mathematics and Statistics, The University of Sydney, Sydney, NSW 2006, Australia.

BMC Bioinformatics
|December 25, 2019
PubMed
Summary
This summary is machine-generated.

We developed single cell differential composition (scDC) analysis to accurately estimate cell-type proportions and their uncertainty from single-cell RNA sequencing data. This method improves comparisons across subjects and conditions.

Keywords:
Composition analysisRNA-seqSingle cellscRNA-seq

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Area of Science:

  • Computational Biology
  • Genomics
  • Bioinformatics

Background:

  • Cell-type composition analysis is crucial for understanding biological variation.
  • Single-cell sequencing offers detailed insights but faces challenges in precise cell-type identification and sampling variability.
  • Accurate estimation of uncertainty in cell-type composition is necessary.

Purpose of the Study:

  • To develop a novel statistical method for differential cell-type composition analysis.
  • To address the challenges of uncertainty estimation in single-cell RNA sequencing data.
  • To provide a robust tool for comparing cell-type proportions across samples and conditions.

Main Methods:

  • Developed single cell differential composition (scDC) analysis.
  • Employed bootstrap resampling for uncertainty estimation.
  • Utilized bias-corrected and accelerated bootstrap confidence intervals.
  • Validated using simulated and publicly available single-cell datasets.

Main Results:

  • scDC accurately recovered true cell-type proportions in simulated datasets.
  • scDC demonstrated high concordance with reference compositions in synthetic datasets.
  • Confidence intervals enabled improved comparisons of compositional differences, especially with small sample sizes (2-5 subjects per condition).

Conclusions:

  • scDC is a novel statistical method for differential cell-type composition analysis in scRNA-seq data.
  • The method estimates standard errors and performs significance testing using GLM and GLMM models.
  • scDC is available as part of the scdney R package for the scientific community.