SRCP: a comprehensive pipeline for accurate annotation and quantification of circRNAs

Avigayel Rabin,Liran Carmel,Sebastian Kadener,Shlomo Shenzis,Ines Lucia Patop,Aarti Jajoo,Michela Zaffagni,Reut Ashwal-Fluss

doi:10.1186/s13059-021-02497-7

Avigayel Rabin, Liran Carmel + Show 6 more

Open Access

https://doi.org/10.1186/s13059-021-02497-7

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Journal: Genome Biology	Publication Date: Sep 23, 2021
Citations: 11	License type: open-access

Affiliation: Hebrew University of Jerusalem, Brandeis University

Abstract

Here we describe a new integrative approach for accurate annotation and quantification of circRNAs named Short Read circRNA Pipeline (SRCP). Our strategy involves two steps: annotation of validated circRNAs followed by a quantification step. We show that SRCP is more sensitive than other individual pipelines and allows for more comprehensive quantification of a larger number of differentially expressed circRNAs. To facilitate the use of SRCP, we generate a comprehensive collection of validated circRNAs in five different organisms, including humans. We then utilize our approach and identify a subset of circRNAs bound to the miRNA-effector protein AGO2 in human brain samples.

Highlights

Circular RNAs are abundant RNAs generated through circularization of specific exons by a process called back splicing [1,2,3,4]. circRNAs have been found in bacteria, archaea, and most eukaryotes [5]
As annotation of the boundaries of circRNAs can be ambiguous between reads and/or between pipelines, we score the potential boundaries for a circRNA depending on the presence of zero, one, or two annotated spliced junctions
CircRNAs that are detected by several pipelines and are expressed at medium to high levels are usually real, even if slightly sensitive to RNaseR

Summary

Introduction

Circular RNAs (circRNAs) are abundant RNAs generated through circularization of specific exons by a process called back splicing [1,2,3,4]. circRNAs have been found in bacteria, archaea, and most eukaryotes [5]. CircRNAs have been found in bacteria, archaea, and most eukaryotes [5]. While circRNAs are produced by splicing in most eukaryotes, it is not clear how are they produced in bacteria and archaea [4]. Other studies showed that these molecules can regulate the activity of RNA-binding proteins [13] and ribosome biogenesis [14] and that a subset of them encode proteins [15,16,17].

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