An isoform-resolution transcriptomic atlas of colorectal cancer from long-read single-cell sequencing
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.
Authors
- Xiao Hong Chew
- Yvonne Tay (ORCID: https://orcid.org/0000-0003-4989-9101)
- Bettina Lieske (ORCID: https://orcid.org/0000-0001-6221-3974)
- Jia Jia Chan (ORCID: https://orcid.org/0000-0001-6110-4979)
- Charlene Chan
- Kai-Yin Lee
- Dennis Kappei (ORCID: https://orcid.org/0000-0002-3582-2253)
- Hossein Tabatabaeian (ORCID: https://orcid.org/0000-0001-9757-6150)
- Xiaonan Fan (ORCID: https://orcid.org/0000-0003-3308-2201)
- Ian Jse-Wei Tan (ORCID: https://orcid.org/0000-0002-1923-0653)
- Ker‐Kan Tan (ORCID: https://orcid.org/0000-0002-0410-0450)
- Qing Tong (ORCID: https://orcid.org/0000-0003-1566-1090)
- Patrick Driguez (ORCID: https://orcid.org/0000-0001-8104-677X)
- Faith Cheong
- Bin Zhang (ORCID: https://orcid.org/0000-0001-8835-8370)
- Shi Wang (ORCID: https://orcid.org/0000-0001-8335-4178)
- Xin D. Gao (ORCID: https://orcid.org/0000-0002-7108-3574)
- Zhongxiao Li (ORCID: https://orcid.org/0000-0003-2480-0750)
- Wai‐Kit Cheong
- Bei En Siew
Institutions
- National University of Singapore (SG)
- National University Cancer Institute, Singapore (SG)
- National University Health System (SG)
- King Abdullah University of Science and Technology (SA)
Publication Details
- Journal
- Cell Genomics
- Published
- 2024-08-30
- DOI
- https://doi.org/10.1016/j.xgen.2024.100641
- Citations
- 13
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 3.04
Funders
- National Research Foundation
- National Research Foundation Singapore
- King Abdullah University of Science and Technology
- National Medical Research Council