The bioinformatics toolbox for circRNA discovery and analysis

Abstract

Circular RNAs (circRNAs) are a unique class of RNA molecule identified more than 40 years ago which are produced by a covalent linkage via back-splicing of linear RNA. Recent advances in sequencing technologies and bioinformatics tools have led directly to an ever-expanding field of types and biological functions of circRNAs. In parallel with technological developments, practical applications of circRNAs have arisen including their utilization as biomarkers of human disease. Currently, circRNA-associated bioinformatics tools can support projects including circRNA annotation, circRNA identification and network analysis of competing endogenous RNA (ceRNA). In this review, we collected about 100 circRNA-associated bioinformatics tools and summarized their current attributes and capabilities. We also performed network analysis and text mining on circRNA tool publications in order to reveal trends in their ongoing development.

Sensitive, reliable, and robust circRNA detection from RNA-seq with CirComPara2

“…Studies of circRNAs rapidly increased in pace with the development of bioinformatics approaches that identify the sequences spanning circRNA back-splice junctions from total RNA-seq data. To date, several methods for circRNA identification have been developed 2 , but none clearly outperforms the others since they provide either highly sensitive or highly precise predictions 3–6 . CircRNA detection algorithms employ filtering procedures 3–6 that remove false-positive guesses (FPs) to improve precision, but that may also reject true circRNAs, thus increasing the number of false-negative predictions (FNs).…”

The Expression, Functions and Mechanisms of Circular RNAs in Gynecological Cancers

“…CircRNAs were first discovered in the 1970s [ 8 , 9 ] and were initially thought to be a non-functional by-product of aberrant splicing in cells [ 10 ]. However, recent advances in sequencing technologies have revealed that large numbers of circRNAs are broadly expressed in a wide range of mammalian tissue [ 11 ]. Over 30,000 circRNAs have already been found in human tissues [ 12 ].…”

Circular RNAs: A New Piece in the Colorectal Cancer Puzzle

“…For the identification based on the back-splice junction, either segmented reads or a pseudo-reference can be used. The first approach is based on splitting the sequencing reads, whereas the latter is based on a pre-defined back-splice junction and its flanking sequences in a circRNA; next, the sequencing read is directly mapped against this pseudo-reference for identification of a back-splice site [ 106 ].…”

“…This can be achieved via treatment of total RNA with RNase R, an exoribonuclease which degrades linear RNA molecules, poly(A) depletion, rRNA depletion, or combination of the aforementioned strategies. circRNA sequencing reads can be either single-end or paired-end [ 106 ].…”