Abstract
Recent studies reveal that circular RNAs (circRNAs) are a novel class of abundant, stable and ubiquitous noncoding RNA molecules in animals. Comprehensive detection of circRNAs from high-throughput transcriptome data is an initial and crucial step to study their biogenesis and function. Here, we present a novel chiastic clipping signal-based algorithm, CIRI, to unbiasedly and accurately detect circRNAs from transcriptome data by employing multiple filtration strategies. By applying CIRI to ENCODE RNA-seq data, we for the first time identify and experimentally validate the prevalence of intronic/intergenic circRNAs as well as fragments specific to them in the human transcriptome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-014-0571-3) contains supplementary material, which is available to authorized users.
Highlights
The past 20 years have witnessed much progress in the study of RNAs [1,2]
During the first scanning of Sequence Alignment/ Map (SAM) alignment, CIRI detects junction reads with paired chiastic clipping (PCC) signals that reflect a Circular RNA (circRNA) candidate
After clustering junction reads and recording each circRNA candidate, CIRI scans the SAM alignment again to detect additional junction reads and performs further filtering to eliminate false positive candidates resulting from incorrectly mapped reads of homologous genes or repetitive sequences
Summary
The past 20 years have witnessed much progress in the study of RNAs [1,2]. A large proportion of known RNAs were proved to undertake diverse important biological functions. While in eukaryotes circRNAs were often regarded as transcriptional noise, such as products of mis-splicing events [9], recent studies using high-throughput RNA-seq data analysis and corresponding experimental validation have proved that they represent a class of abundant, stable and ubiquitous RNAs in animals [10,11,12,13]. Their high abundance and evolutionary conservation between species suggest important functions, and studies subsequently revealed that a subset of them function as microRNA sponges [11,14]. The functions of the majority of circRNAs still remain unknown and there are few models of their mechanism of formation, which prevents model-oriented experimental validation to solve the circRNA mystery
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