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Uncovering functional lncRNAs by scRNA-seq with ELATUS

Author

Listed:
  • Enrique Goñi

    (University of Navarra
    Institute of Health Research of Navarra (IdiSNA)
    Cancer Center Clinica Universidad de Navarra (CCUN))

  • Aina Maria Mas

    (University of Navarra
    Institute of Health Research of Navarra (IdiSNA)
    Cancer Center Clinica Universidad de Navarra (CCUN))

  • Jovanna Gonzalez

    (University of Navarra
    Institute of Health Research of Navarra (IdiSNA)
    Cancer Center Clinica Universidad de Navarra (CCUN))

  • Amaya Abad

    (University of Navarra
    Institute of Health Research of Navarra (IdiSNA))

  • Marta Santisteban

    (Institute of Health Research of Navarra (IdiSNA)
    Cancer Center Clinica Universidad de Navarra (CCUN)
    Clinica Universidad de Navarra)

  • Puri Fortes

    (University of Navarra
    Institute of Health Research of Navarra (IdiSNA)
    Cancer Center Clinica Universidad de Navarra (CCUN)
    Spanish Network for Advanced Therapies (TERAV ISCIII))

  • Maite Huarte

    (University of Navarra
    Institute of Health Research of Navarra (IdiSNA)
    Cancer Center Clinica Universidad de Navarra (CCUN))

  • Mikel Hernaez

    (University of Navarra
    Institute of Health Research of Navarra (IdiSNA)
    Cancer Center Clinica Universidad de Navarra (CCUN)
    Universidad de Navarra)

Abstract

Long non-coding RNAs (lncRNAs) play fundamental roles in cellular processes and pathologies, regulating gene expression at multiple levels. Despite being highly cell type-specific, their study at single-cell (sc) level is challenging due to their less accurate annotation and low expression compared to protein-coding genes. Here, we systematically benchmark different preprocessing methods and develop a computational framework, named ELATUS, based on the combination of the pseudoaligner Kallisto with selective functional filtering. ELATUS enhances the detection of functional lncRNAs from scRNA-seq data, detecting their expression with higher concordance than standard methods with the ATAC-seq profiles in single-cell multiome data. Interestingly, the better results of ELATUS are due to its advanced performance with an inaccurate reference annotation such as that of lncRNAs. We independently confirm the expression patterns of cell type-specific lncRNAs exclusively detected with ELATUS and unveil biologically important lncRNAs, such as AL121895.1, a previously undocumented cis-repressor lncRNA, whose role in breast cancer progression is unnoticed by traditional methodologies. Our results emphasize the necessity for an alternative scRNA-seq workflow tailored to lncRNAs that sheds light on the multifaceted roles of lncRNAs.

Suggested Citation

  • Enrique Goñi & Aina Maria Mas & Jovanna Gonzalez & Amaya Abad & Marta Santisteban & Puri Fortes & Maite Huarte & Mikel Hernaez, 2024. "Uncovering functional lncRNAs by scRNA-seq with ELATUS," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54005-7
    DOI: 10.1038/s41467-024-54005-7
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    References listed on IDEAS

    as
    1. Beate Vieth & Swati Parekh & Christoph Ziegenhain & Wolfgang Enard & Ines Hellmann, 2019. "A systematic evaluation of single cell RNA-seq analysis pipelines," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    2. Sarah Aldridge & Sarah A. Teichmann, 2020. "Single cell transcriptomics comes of age," Nature Communications, Nature, vol. 11(1), pages 1-4, December.
    3. Gioele La Manno & Ruslan Soldatov & Amit Zeisel & Emelie Braun & Hannah Hochgerner & Viktor Petukhov & Katja Lidschreiber & Maria E. Kastriti & Peter Lönnerberg & Alessandro Furlan & Jean Fan & Lars E, 2018. "RNA velocity of single cells," Nature, Nature, vol. 560(7719), pages 494-498, August.
    4. Kelvin See & Wilson L. W. Tan & Eng How Lim & Zenia Tiang & Li Ting Lee & Peter Y. Q. Li & Tuan D. A. Luu & Matthew Ackers-Johnson & Roger S. Foo, 2017. "Single cardiomyocyte nuclear transcriptomes reveal a lincRNA-regulated de-differentiation and cell cycle stress-response in vivo," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
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