Quantifying full-length circular RNAs in cancer
- Ken Hung-On Yu1,2,7,
- Christina Huan Shi2,7,
- Bo Wang1,
- Savio Ho-Chit Chow2,3,
- Grace Tin-Yun Chung1,
- Raymond Wai-Ming Lung1,
- Ke-En Tan4,
- Yat-Yuen Lim4,
- Anna Chi-Man Tsang1,
- Kwok-Wai Lo1 and
- Kevin Y. Yip2,5,6
- 1Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong;
- 2Department of Computer Science and Engineering, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong;
- 3School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong;
- 4Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia;
- 5Hong Kong Bioinformatics Centre, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong;
- 6Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
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↵7 These authors contributed equally to this work.
Abstract
Circular RNAs (circRNAs) are abundantly expressed in cancer. Their resistance to exonucleases enables them to have potentially stable interactions with different types of biomolecules. Alternative splicing can create different circRNA isoforms that have different sequences and unequal interaction potentials. The study of circRNA function thus requires knowledge of complete circRNA sequences. Here we describe psirc, a method that can identify full-length circRNA isoforms and quantify their expression levels from RNA sequencing data. We confirm the effectiveness and computational efficiency of psirc using both simulated and actual experimental data. Applying psirc on transcriptome profiles from nasopharyngeal carcinoma and normal nasopharynx samples, we discover and validate circRNA isoforms differentially expressed between the two groups. Compared with the assumed circular isoforms derived from linear transcript annotations, some of the alternatively spliced circular isoforms have 100 times higher expression and contain substantially fewer microRNA response elements, showing the importance of quantifying full-length circRNA isoforms.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.275348.121.
- Received February 4, 2021.
- Accepted October 12, 2021.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see https://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
