Detecting circular RNAs: bioinformatic and experimental challenges

TL;DR: This work reviews sources of experimental and bioinformatic biases that complicate the accurate discovery of circRNAs and discusses statistical approaches to address these biases.

Abstract: The pervasive expression of circular RNAs (circRNAs) is a recently discovered feature of gene expression in highly diverged eukaryotes. Numerous algorithms that are used to detect genome-wide circRNA expression from RNA sequencing (RNA-seq) data have been developed in the past few years, but there is little overlap in their predictions and no clear gold-standard method to assess the accuracy of these algorithms. We review sources of experimental and bioinformatic biases that complicate the accurate discovery of circRNAs and discuss statistical approaches to address these biases. We conclude with a discussion of the current experimental progress on the topic.