biostudies-literatureGoni E"la Caixa" Foundation (Caixa Foundation)EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions)Worldwide Cancer ResearchEuropean Research CouncilDepartamento de Educación, Gobierno de Navarra (Department of Education, Government of Navarra)9709https://www.ebi.ac.uk/biostudies/studies/S-EPMC11550465biostudies-literatureUnknown15(1)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 adNature communicationsUncovering functional lncRNAs by scRNA-seq with ELATUS.PMC11550465898356LCF/PR/HR21/0017620-02040011-0537-2020-000038771425Hernaez MSantisteban MGonzalez JAbad AFortes PHuarte MMas AMGoni EfalseUncovering functional lncRNAs by scRNA-seq with ELATUS.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 ad2024-01-01T00:00:00Z2024 Nov2026-06-03T03:17:37.254Z2025-04-06T22:42:42.419ZS-EPMC115504653952179710.1038/s41467-024-54005-7