*Result*: ELLIPSIS: robust quantification of splicing in scRNA-seq.

Title:
ELLIPSIS: robust quantification of splicing in scRNA-seq.
Authors:
Van Hecke M; IDLab, Department of Information Technology, Ghent University-IMEC, 9052 Ghent, Belgium.; Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium., Beerenwinkel N; Department of Biosystems Science and Engineering, ETH Zürich, 4056 Basel, Switzerland.; SIB Swiss Institute of Bioinformatics, 4051 Basel, Switzerland., Lootens T; Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium.; 4Brain, Department of Head and Skin, Ghent University, 9000 Ghent, Belgium.; Laboratory of Experimental Cancer Research, Department of Human Structure and Repair, Ghent University, 9000 Ghent, Belgium., Fostier J; Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium., Raedt R; Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium.; 4Brain, Department of Head and Skin, Ghent University, 9000 Ghent, Belgium., Marchal K; IDLab, Department of Information Technology, Ghent University-IMEC, 9052 Ghent, Belgium.; Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium.
Source:
Bioinformatics (Oxford, England) [Bioinformatics] 2025 Feb 04; Vol. 41 (2).
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Oxford University Press Country of Publication: England NLM ID: 9808944 Publication Model: Print Cited Medium: Internet ISSN: 1367-4811 (Electronic) Linking ISSN: 13674803 NLM ISO Abbreviation: Bioinformatics Subsets: MEDLINE
Imprint Name(s):
Original Publication: Oxford : Oxford University Press, c1998-
MeSH Terms:
Single-Cell Analysis*/methods , RNA-Seq*/methods , Sequence Analysis, RNA*/methods , Alternative Splicing* , Software* , RNA Splicing*, Glioblastoma/genetics ; Humans ; Algorithms ; Single-Cell Gene Expression Analysis
References:
Nat Rev Genet. 2013 Jul;14(7):496-506. (PMID: 23774734)
Cancers (Basel). 2022 Jan 17;14(2):. (PMID: 35053605)
Nucleic Acids Res. 2022 Jan 7;50(D1):D287-D294. (PMID: 34403477)
Nat Commun. 2023 Mar 3;14(1):1230. (PMID: 36869033)
Nat Biotechnol. 2020 Jun;38(6):708-714. (PMID: 32518404)
Genome Biol. 2021 Aug 27;22(1):251. (PMID: 34452629)
Front Cell Neurosci. 2014 Nov 13;8:373. (PMID: 25431548)
BMC Bioinformatics. 2020 Sep 14;21(1):402. (PMID: 32928110)
Nucleic Acids Res. 2018 Sep 28;46(17):9106-9118. (PMID: 29901772)
Nat Protoc. 2014 Jan;9(1):171-81. (PMID: 24385147)
Science. 2016 Apr 29;352(6285):600-4. (PMID: 27126046)
Biomedicines. 2022 Jan 10;10(1):. (PMID: 35052820)
Front Mol Biosci. 2021 Nov 23;8:726902. (PMID: 34888349)
Nat Biotechnol. 2010 May;28(5):511-5. (PMID: 20436464)
Nat Commun. 2019 Jun 13;10(1):2611. (PMID: 31197158)
J Neurosurg. 2019 Apr 26;132(5):1465-1472. (PMID: 31026822)
Cell Genom. 2022 Dec 30;3(1):100244. (PMID: 36777183)
Cell. 2022 Aug 4;185(16):2899-2917.e31. (PMID: 35914528)
Nat Genet. 2000 May;25(1):25-9. (PMID: 10802651)
Nat Methods. 2010 Dec;7(12):1009-15. (PMID: 21057496)
Nat Commun. 2022 Feb 28;13(1):1084. (PMID: 35228538)
Nat Biotechnol. 2022 Oct;40(10):1452-1457. (PMID: 35637418)
BMC Biol. 2023 Oct 20;21(1):220. (PMID: 37858135)
Cell Rep. 2017 Oct 31;21(5):1399-1410. (PMID: 29091775)
Nat Genet. 2018 Jan;50(1):151-158. (PMID: 29229983)
Nature. 2020 Feb;578(7793):129-136. (PMID: 32025019)
Int J Mol Sci. 2019 Apr 26;20(9):. (PMID: 31027366)
Nature. 2022 Aug;608(7922):353-359. (PMID: 35922509)
Genome Biol. 2021 May 25;22(1):163. (PMID: 34034771)
Nucleic Acids Res. 2013 Jan;41(Database issue):D125-31. (PMID: 23118479)
Nat Biotechnol. 2024 Feb;42(2):293-304. (PMID: 37231261)
Cell. 2017 Nov 30;171(6):1316-1325.e12. (PMID: 29129375)
Front Immunol. 2024 Jun 20;15:1422113. (PMID: 38966643)
Cancers (Basel). 2022 Mar 04;14(5):. (PMID: 35267626)
Elife. 2016 Mar 25;5:. (PMID: 27015110)
Cold Spring Harb Perspect Biol. 2017 Apr 3;9(4):. (PMID: 28096261)
Genetics. 2023 May 4;224(1):. (PMID: 36866529)
Bioinformatics. 2015 Sep 1;31(17):2778-84. (PMID: 25926345)
Mol Biol Cell. 2018 Oct 15;29(21):2509-2515. (PMID: 30325290)
F1000Res. 2021 May 11;10:374. (PMID: 36762203)
Nat Methods. 2017 Apr;14(4):417-419. (PMID: 28263959)
Genome Res. 2022 Jul 27;32(7):1385-1397. (PMID: 35858747)
Anal Cell Pathol (Amst). 2020 Jan 31;2020:9274016. (PMID: 32089990)
Grant Information:
3G045620 Fonds Wetenschappelijk Onderzoek-Vlaanderen; 01J06219 UGent Bijzonder Onderzoeksfonds; S004824N Strategisch BasisOnderzoek
Entry Date(s):
Date Created: 20250212 Date Completed: 20250507 Latest Revision: 20250507
Update Code:
20260130
PubMed Central ID:
PMC11878791
DOI:
10.1093/bioinformatics/btaf028
PMID:
39936571
Database:
MEDLINE

*Further Information*

*Motivation: Alternative splicing is a tightly regulated biological process, that due to its cell type specific behavior, calls for analysis at the single cell level. However, quantifying differential splicing in scRNA-seq is challenging due to low and uneven coverage. Hereto, we developed ELLIPSIS, a tool for robust quantification of splicing in scRNA-seq that leverages locally observed read coverage with conservation of flow and intra-cell type similarity properties. Additionally, it is also able to quantify splicing in novel splicing events, which is extremely important in cancer cells where lots of novel splicing events occur.
Results: Application of ELLIPSIS to simulated data proves that our method is able to robustly estimate Percent Spliced In values in simulated data, and allows to reliably detect differential splicing between cell types. Using ELLIPSIS on glioblastoma scRNA-seq data, we identified genes that are differentially spliced between cancer cells in the tumor core and infiltrating cancer cells found in peripheral tissue. These genes showed to play a role in a.o. cell migration and motility, cell projection organization, and neuron projection guidance.
Availability and Implementation: ELLIPSIS quantification tool: https://github.com/MarchalLab/ELLIPSIS.git.
(© The Author(s) 2025. Published by Oxford University Press.)*