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ELLIPSIS: robust quantification of splicing in scRNA-seq.

Marie Van Hecke1,2,3, Niko Beerenwinkel4,5, Thibault Lootens3,6,7

  • 1IDLab, Department of Information Technology, Ghent University-IMEC, 9052 Ghent, Belgium.

Bioinformatics (Oxford, England)
|February 12, 2025
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Summary
This summary is machine-generated.

A new tool, ELLIPSIS, robustly quantifies alternative splicing in single-cell RNA sequencing (scRNA-seq) data. It identifies differential splicing in cancer cells, revealing genes involved in cell migration and guidance.

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Area of Science:

  • Genomics
  • Computational Biology
  • Molecular Biology

Background:

  • Alternative splicing is a crucial, cell-type-specific regulatory process.
  • Quantifying splicing in single-cell RNA sequencing (scRNA-seq) is difficult due to low and uneven data coverage.

Purpose of the Study:

  • To develop a robust method for quantifying alternative splicing in scRNA-seq data.
  • To enable the detection of differential splicing, including novel splicing events, particularly in cancer cells.

Main Methods:

  • Developed ELLIPSIS, a computational tool for splicing quantification.
  • Leveraged local read coverage, flow conservation, and intra-cell type similarity.
  • Applied ELLIPSIS to simulated and glioblastoma scRNA-seq data.

Main Results:

  • ELLIPSIS accurately estimates Percent Spliced In values from simulated data.
  • The tool reliably detects differential splicing between cell types.
  • Identified differentially spliced genes in glioblastoma, linked to cell migration and neuronal guidance.

Conclusions:

  • ELLIPSIS provides a robust solution for splicing analysis in scRNA-seq.
  • The identified genes offer insights into glioblastoma progression and cell behavior.