Reconstruction of Full-length Circular RNAs Enables Isoform-level Quantification

Overview

Journal Genome Med

Publisher Biomed Central

Specialty Genetics

Date 2019 Jan 21

PMID 30660194

Citations 86

Authors

Yi Zheng

Peifeng Ji

Shuai Chen

Lingling Hou

Fangqing Zhao

Affiliations

Soon will be listed here.

Abstract

Currently, circRNA studies are shifting from the identification of circular transcripts to understanding their biological functions. However, such endeavors have been limited by large-scale determination of their full-length sequences and also by the inability of accurate quantification at the isoform level. Here, we propose a new feature, reverse overlap (RO), for circRNA detection, which outperforms back-splice junction (BSJ)-based methods in identifying low-abundance circRNAs. By combining RO and BSJ features, we present a novel approach for effective reconstruction of full-length circRNAs and isoform-level quantification from the transcriptome. We systematically compared the difference between the BSJ-level and isoform-level differential expression analyses using human liver tumor and normal tissues and highlight the necessity of deepening circRNA studies to the isoform-level resolution. The CIRI-full software can be accessed at https://sourceforge.net/projects/ciri .

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References

Pertea M, Kim D, Pertea G, Leek J, Salzberg S . Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat Protoc. 2016; 11(9):1650-67. PMC: 5032908. DOI: 10.1038/nprot.2016.095. View

Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O . Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis. Mol Cell. 2017; 66(1):22-37.e9. PMC: 5387670. DOI: 10.1016/j.molcel.2017.02.017. View

Chen Y, Satpathy A, Chang H . Gene regulation in the immune system by long noncoding RNAs. Nat Immunol. 2017; 18(9):962-972. PMC: 9830650. DOI: 10.1038/ni.3771. View

Yang Y, Gao X, Zhang M, Yan S, Sun C, Xiao F . Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis. J Natl Cancer Inst. 2017; 110(3). PMC: 6019044. DOI: 10.1093/jnci/djx166. View

Zeng X, Lin W, Guo M, Zou Q . A comprehensive overview and evaluation of circular RNA detection tools. PLoS Comput Biol. 2017; 13(6):e1005420. PMC: 5466358. DOI: 10.1371/journal.pcbi.1005420. View

Gao Y, Wang J, Zhao F . CIRI: an efficient and unbiased algorithm for de novo circular RNA identification. Genome Biol. 2015; 16:4. PMC: 4316645. DOI: 10.1186/s13059-014-0571-3. View

Haas B, Papanicolaou A, Yassour M, Grabherr M, Blood P, Bowden J . De novo transcript sequence reconstruction from RNA-seq using the Trinity platform for reference generation and analysis. Nat Protoc. 2013; 8(8):1494-512. PMC: 3875132. DOI: 10.1038/nprot.2013.084. View

Hirsch S, Blatte T, Grasedieck S, Cocciardi S, Rouhi A, Jongen-Lavrencic M . Circular RNAs of the nucleophosmin (NPM1) gene in acute myeloid leukemia. Haematologica. 2017; 102(12):2039-2047. PMC: 5709103. DOI: 10.3324/haematol.2017.172866. View

Ashwal-Fluss R, Meyer M, Pamudurti N, Ivanov A, Bartok O, Hanan M . circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014; 56(1):55-66. DOI: 10.1016/j.molcel.2014.08.019. View

10.

Piwecka M, Glazar P, Hernandez-Miranda L, Memczak S, Wolf S, Rybak-Wolf A . Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science. 2017; 357(6357). DOI: 10.1126/science.aam8526. View

11.

Li Z, Huang C, Bao C, Chen L, Lin M, Wang X . Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 2015; 22(3):256-64. DOI: 10.1038/nsmb.2959. View

12.

Wang J, Liu K, Liu Y, Lv Q, Zhang F, Wang H . Evaluating the bias of circRNA predictions from total RNA-Seq data. Oncotarget. 2018; 8(67):110914-110921. PMC: 5762294. DOI: 10.18632/oncotarget.22972. View

13.

Salzman J, Gawad C, Wang P, Lacayo N, Brown P . Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One. 2012; 7(2):e30733. PMC: 3270023. DOI: 10.1371/journal.pone.0030733. View

14.

Heber S, Alekseyev M, Sze S, Tang H, Pevzner P . Splicing graphs and EST assembly problem. Bioinformatics. 2002; 18 Suppl 1:S181-8. DOI: 10.1093/bioinformatics/18.suppl_1.s181. View

15.

Szabo L, Morey R, Palpant N, Wang P, Afari N, Jiang C . Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development. Genome Biol. 2015; 16:126. PMC: 4506483. DOI: 10.1186/s13059-015-0690-5. View

16.

Zhou C, Molinie B, Daneshvar K, Pondick J, Wang J, Van Wittenberghe N . Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs. Cell Rep. 2017; 20(9):2262-2276. PMC: 5705222. DOI: 10.1016/j.celrep.2017.08.027. View

17.

Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B . Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016; 7:11215. PMC: 4823868. DOI: 10.1038/ncomms11215. View

18.

Zhang X, Wang H, Zhang Y, Lu X, Chen L, Yang L . Complementary sequence-mediated exon circularization. Cell. 2014; 159(1):134-147. DOI: 10.1016/j.cell.2014.09.001. View

19.

Fei T, Chen Y, Xiao T, Li W, Cato L, Zhang P . Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proc Natl Acad Sci U S A. 2017; 114(26):E5207-E5215. PMC: 5495225. DOI: 10.1073/pnas.1617467114. View

20.

Salzman J, Chen R, Olsen M, Wang P, Brown P . Cell-type specific features of circular RNA expression. PLoS Genet. 2013; 9(9):e1003777. PMC: 3764148. DOI: 10.1371/journal.pgen.1003777. View