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Multiscale Methods for Signal Selection in Single-Cell Data.

Renee S Hoekzema1,2, Lewis Marsh1,3, Otto Sumray1,3

  • 1Mathematical Institute, University of Oxford, Oxford OX1 2JD, UK.

Entropy (Basel, Switzerland)
|August 26, 2022
PubMed
Summary
This summary is machine-generated.

We introduce three novel unsupervised methods for analyzing single-cell transcriptomics data. These topological approaches identify genes with continuous and discrete expression patterns, revealing new biological insights.

Keywords:
feature selectionmultiscale data analysispersistent Laplaciansingle cell transcriptomicstopological signal processing

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Area of Science:

  • Computational Biology
  • Genomics
  • Data Science

Background:

  • Single-cell transcriptomics analysis commonly uses clustering and differential gene expression (DGE).
  • These methods primarily identify discrete cell types and markers.
  • Continuous biological variation within and between cell types may be missed.

Purpose of the Study:

  • To develop unsupervised feature selection methods for single-cell transcriptomics.
  • To analyze both discrete and continuous transcriptional patterns simultaneously.
  • To identify genes with coherent expression patterns across multiple scales.

Main Methods:

  • Eigenscores (eigi): Spectral decomposition of Laplacian graph for low-frequency patterning.
  • Multiscale Laplacian score (MLS): Identifies relevant scales and coherently expressed genes.
  • Persistent Rayleigh quotient (PRQ): Separates genes involved in bifurcation processes (e.g., pseudotime).

Main Results:

  • Applied methods to published single-cell transcriptomics datasets.
  • Validated previously identified marker genes.
  • Discovered additional biologically meaningful genes with coherent expression patterns.
  • Provided multidimensional gene rankings and visualizations of gene relationships.

Conclusions:

  • The proposed topological methods offer a powerful alternative to traditional DGE analysis.
  • These techniques capture complex gene expression patterns, including continuous variation.
  • The methods enhance the understanding of cellular heterogeneity and dynamics.