Reconstruction of full-length circular RNAs enables isoform-level quantification

Genome Med. 2019 Jan 19;11(1):2. doi: 10.1186/s13073-019-0614-1.

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 .

Keywords: Alternative splicing; Circular RNA (circRNA); Isoform quantification; Transcript reconstruction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • HeLa Cells
  • Humans
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA / genetics*
  • RNA / metabolism
  • RNA, Circular
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Analysis, RNA / methods*
  • Software*

Substances

  • Protein Isoforms
  • RNA, Circular
  • RNA, Messenger
  • RNA