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Accurate long-read transcript discovery and quantification at single-cell, pseudo-bulk and bulk resolution with Isosceles

Author

Listed:
  • Michal Kabza

    (F. Hoffmann-La Roche Ltd)

  • Alexander Ritter

    (Genentech Inc.)

  • Ashley Byrne

    (Genentech Inc.)

  • Kostianna Sereti

    (Genentech Inc.)

  • Daniel Le

    (Genentech Inc.)

  • William Stephenson

    (Genentech Inc.)

  • Timothy Sterne-Weiler

    (Genentech Inc.
    Genentech Inc.)

Abstract

Accurate detection and quantification of mRNA isoforms from nanopore long-read sequencing remains challenged by technical noise, particularly in single cells. To address this, we introduce Isosceles, a computational toolkit that outperforms other methods in isoform detection sensitivity and quantification accuracy across single-cell, pseudo-bulk and bulk resolution levels, as demonstrated using synthetic and biologically-derived datasets. Here we show Isosceles improves the fidelity of single-cell transcriptome quantification at the isoform-level, and enables flexible downstream analysis. As a case study, we apply Isosceles, uncovering coordinated splicing within and between neuronal differentiation lineages. Isosceles is suitable to be applied in diverse biological systems, facilitating studies of cellular heterogeneity across biomedical research applications.

Suggested Citation

  • Michal Kabza & Alexander Ritter & Ashley Byrne & Kostianna Sereti & Daniel Le & William Stephenson & Timothy Sterne-Weiler, 2024. "Accurate long-read transcript discovery and quantification at single-cell, pseudo-bulk and bulk resolution with Isosceles," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51584-3
    DOI: 10.1038/s41467-024-51584-3
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    References listed on IDEAS

    as
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