*Result*: An isoform-resolution transcriptomic atlas of colorectal cancer from long-read single-cell sequencing.
Title:
An isoform-resolution transcriptomic atlas of colorectal cancer from long-read single-cell sequencing.
Authors:
Li Z; Computer Science Program, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia; Center of Excellence for Smart Health (KCSH), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia; Center of Excellence on Generative AI, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia., Zhang B; Computer Science Program, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia; Center of Excellence for Smart Health (KCSH), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia; Center of Excellence on Generative AI, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia. Electronic address: bin.zhang@kaust.edu.sa., Chan JJ; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore., Tabatabaeian H; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore., Tong QY; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore., Chew XH; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore., Fan X; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore., Driguez P; Core Labs, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia., Chan C; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore., Cheong F; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore., Wang S; Department of Pathology, National University Health System, Singapore 119228, Singapore., Siew BE; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore., Tan IJ; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Division of Colorectal Surgery, University Surgical Cluster, National University Health System, Singapore 119228, Singapore., Lee KY; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Division of Colorectal Surgery, University Surgical Cluster, National University Health System, Singapore 119228, Singapore., Lieske B; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Division of Colorectal Surgery, University Surgical Cluster, National University Health System, Singapore 119228, Singapore., Cheong WK; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Division of Colorectal Surgery, University Surgical Cluster, National University Health System, Singapore 119228, Singapore., Kappei D; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore., Tan KK; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Division of Colorectal Surgery, University Surgical Cluster, National University Health System, Singapore 119228, Singapore., Gao X; Computer Science Program, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia; Center of Excellence for Smart Health (KCSH), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia; Center of Excellence on Generative AI, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia. Electronic address: xin.gao@kaust.edu.sa., Tay Y; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. Electronic address: yvonnetay@nus.edu.sg.
Source:
Cell genomics [Cell Genom] 2024 Sep 11; Vol. 4 (9), pp. 100641. Date of Electronic Publication: 2024 Aug 30.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Elsevier, Inc Country of Publication: United States NLM ID: 9918284260106676 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-979X (Electronic) Linking ISSN: 2666979X NLM ISO Abbreviation: Cell Genom Subsets: MEDLINE
Imprint Name(s):
Original Publication: [New York] : Elsevier, Inc., [2021]-
MeSH Terms:
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Science. 2007 Nov 16;318(5853):1108-13. (PMID: 17932254)
Bioinformatics. 2017 Nov 01;33(21):3387-3395. (PMID: 29036616)
BMC Bioinformatics. 2009 Dec 15;10:421. (PMID: 20003500)
Cell. 2019 Sep 5;178(6):1465-1477.e17. (PMID: 31491388)
Nature. 2013 Sep 19;501(7467):328-37. (PMID: 24048065)
Nat Methods. 2015 Jun;12(6):519-22. (PMID: 25915121)
Nature. 2019 Jan;565(7738):234-239. (PMID: 30568305)
Nat Cell Biol. 2022 Jun;24(6):928-939. (PMID: 35618746)
Nat Biotechnol. 2018 Dec 17;:. (PMID: 30556813)
Crit Rev Toxicol. 1993;23(1):77-109. (PMID: 8097093)
Nature. 2017 Oct 11;550(7675):249-254. (PMID: 29022589)
F1000Res. 2020 Apr 28;9:304. (PMID: 32489650)
Annu Rev Biochem. 2010;79:321-49. (PMID: 20192758)
Nucleic Acids Res. 2014 Jan;42(Database issue):D109-13. (PMID: 24163250)
PLoS One. 2012;7(3):e33720. (PMID: 22448268)
Nat Biotechnol. 2024 Apr;42(4):582-586. (PMID: 37291427)
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D138-41. (PMID: 14681378)
Nat Commun. 2014 Nov 20;5:5274. (PMID: 25409906)
J Am Soc Mass Spectrom. 2016 Nov;27(11):1719-1727. (PMID: 27572102)
J Mol Biol. 2019 Jun 14;431(13):2407-2422. (PMID: 31075273)
Nat Med. 2015 Nov;21(11):1350-6. (PMID: 26457759)
Sci Adv. 2022 Jan 21;8(3):eabg6711. (PMID: 35044822)
Cell Physiol Biochem. 2018;47(6):2602-2612. (PMID: 29996118)
Nat Commun. 2018 Sep 25;9(1):3919. (PMID: 30254248)
Nature. 2013 Sep 19;501(7467):338-45. (PMID: 24048066)
Nucleic Acids Res. 2019 Jul 2;47(W1):W199-W205. (PMID: 31114916)
Bioinformatics. 2020 Jan 1;36(1):33-40. (PMID: 31173059)
Cancer Sci. 2017 Feb;108(2):178-186. (PMID: 27865045)
Nature. 2017 Jul 13;547(7662):217-221. (PMID: 28678778)
Nucleic Acids Res. 2020 Jan 8;48(D1):D174-D179. (PMID: 31617559)
Nucleic Acids Res. 2013 Jan;41(Database issue):D258-61. (PMID: 23074185)
Genome Biol. 2021 Jan 22;22(1):44. (PMID: 33482911)
EMBO J. 2005 Apr 20;24(8):1608-20. (PMID: 15933722)
Cell. 2021 Sep 2;184(18):4734-4752.e20. (PMID: 34450029)
CA Cancer J Clin. 2021 May;71(3):209-249. (PMID: 33538338)
PLoS Genet. 2017 Feb 6;13(2):e1006563. (PMID: 28166241)
Genome Res. 2018 Mar 1;28(3):396-411. (PMID: 29440222)
Nat Methods. 2017 Oct;14(10):979-982. (PMID: 28825705)
Am J Pathol. 1997 Feb;150(2):483-95. (PMID: 9033265)
Nat Genet. 2022 Jul;54(7):985-995. (PMID: 35726067)
Nature. 2020 Sep;585(7825):357-362. (PMID: 32939066)
Cancer Cell. 2018 Aug 13;34(2):211-224.e6. (PMID: 30078747)
Nucleic Acids Res. 2020 Jul 2;48(W1):W449-W454. (PMID: 32406916)
Br J Cancer. 2001 Feb;84(4):512-9. (PMID: 11207047)
Nat Genet. 2020 Jun;52(6):594-603. (PMID: 32451460)
Biometrika. 1950 Jun;37(1-2):17-23. (PMID: 15420245)
Nat Biotechnol. 2021 Dec;39(12):1517-1520. (PMID: 34211161)
Sci Rep. 2015 Sep 29;5:14548. (PMID: 26416554)
Nat Methods. 2020 Mar;17(3):261-272. (PMID: 32015543)
Nat Methods. 2024 May;21(5):793-797. (PMID: 38509328)
Cancer Discov. 2013 Oct;3(10):1108-12. (PMID: 24124232)
Gigascience. 2021 Feb 16;10(2):. (PMID: 33590861)
Nature. 2013 Jun 13;498(7453):241-5. (PMID: 23739326)
Nat Methods. 2007 Nov;4(11):923-5. (PMID: 17952086)
Mol Cell. 2021 May 20;81(10):2246-2260.e12. (PMID: 33861991)
Anal Bioanal Chem. 2006 Nov;386(6):1603-12. (PMID: 17043799)
Nucleic Acids Res. 2015 Jul 13;43(12):e78. (PMID: 25870408)
Genome Biol. 2018 Mar 23;19(1):40. (PMID: 29571299)
Immunity. 2018 Apr 17;48(4):812-830.e14. (PMID: 29628290)
Nat Genet. 2022 Jul;54(7):963-975. (PMID: 35773407)
Nat Genet. 2017 May;49(5):708-718. (PMID: 28319088)
Cell. 2020 Apr 16;181(2):442-459.e29. (PMID: 32302573)
Cell. 2022 Jul 21;185(15):2770-2788. (PMID: 35835100)
Cell Rep. 2022 Jun 21;39(12):110985. (PMID: 35732114)
Nat Biotechnol. 2018 Dec;36(11):1056-1058. (PMID: 30114007)
J Immunol. 2017 Nov 1;199(9):3360-3368. (PMID: 28978689)
Genome Res. 2018 Oct;28(10):1427-1441. (PMID: 30143597)
Nature. 2012 Jul 18;487(7407):330-7. (PMID: 22810696)
Cell. 2019 Jun 13;177(7):1888-1902.e21. (PMID: 31178118)
Proteomics. 2013 Jan;13(1):22-4. (PMID: 23148064)
Transl Oncol. 2019 Feb;12(2):256-268. (PMID: 30439626)
Semin Cell Dev Biol. 2012 May;23(3):244-50. (PMID: 21930228)
Nucleic Acids Res. 2021 Jan 8;49(D1):D480-D489. (PMID: 33237286)
Bioinformatics. 2018 Sep 15;34(18):3094-3100. (PMID: 29750242)
Nature. 2023 Jun;618(7963):144-150. (PMID: 37165196)
Science. 2007 Nov 16;318(5853):1108-13. (PMID: 17932254)
Bioinformatics. 2017 Nov 01;33(21):3387-3395. (PMID: 29036616)
BMC Bioinformatics. 2009 Dec 15;10:421. (PMID: 20003500)
Cell. 2019 Sep 5;178(6):1465-1477.e17. (PMID: 31491388)
Nature. 2013 Sep 19;501(7467):328-37. (PMID: 24048065)
Nat Methods. 2015 Jun;12(6):519-22. (PMID: 25915121)
Contributed Indexing:
Keywords: colorectal cancer; long-read RNA-seq; neoantigen; scRNA-seq
Substance Nomenclature:
0 (Protein Isoforms)
Entry Date(s):
Date Created: 20240831 Date Completed: 20240912 Latest Revision: 20241019
Update Code:
20260130
PubMed Central ID:
PMC11480860
DOI:
10.1016/j.xgen.2024.100641
PMID:
39216476
Database:
MEDLINE
*Further Information*
*Colorectal cancer (CRC) ranks as the second leading cause of cancer deaths globally. In recent years, short-read single-cell RNA sequencing (scRNA-seq) has been instrumental in deciphering tumor heterogeneities. However, these studies only enable gene-level quantification but neglect alterations in transcript structures arising from alternative end processing or splicing. In this study, we integrated short- and long-read scRNA-seq of CRC samples to build an isoform-resolution CRC transcriptomic atlas. We identified 394 dysregulated transcript structures in tumor epithelial cells, including 299 resulting from various combinations of splicing events. Second, we characterized genes and isoforms associated with epithelial lineages and subpopulations exhibiting distinct prognoses. Among 31,935 isoforms with novel junctions, 330 were supported by The Cancer Genome Atlas RNA-seq and mass spectrometry data. Finally, we built an algorithm that integrated novel peptides derived from open reading frames of recurrent tumor-specific transcripts with mass spectrometry data and identified recurring neoepitopes that may aid the development of cancer vaccines.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)*
*Declaration of interests The authors declare no competing interests.*