Open AccessQuantifying full-length circular RNAs in cancer
Author(s) -
Ken Hung-On Yu,
Christina Huan Shi,
Bo Wang,
Savio Ho-Chit Chow,
Grace TinYun Chung,
Raymond Wai Ming Lung,
Ke-En Tan,
Yat-Yuen Lim,
Anna ChiMan Tsang,
KwokWai Lo,
Kevin Yip
Publication year - 2021
Publication title -
genome research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.556
H-Index - 297
eISSN - 1549-5469
pISSN - 1088-9051
DOI - 10.1101/gr.275348.121
Subject(s) - circular rna , biology , gene isoform , computational biology , alternative splicing , microrna , transcriptome , rna splicing , function (biology) , genetics , rna , gene , gene expression
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.