Accurate quantification of circular RNAs identifies extensive circular isoform switching events

Jinyang Zhang, Shuai Chen, Jingwen Yang and Fangqing Zhao ()
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Jinyang Zhang: Chinese Academy of Sciences
Shuai Chen: Chinese Academy of Sciences
Jingwen Yang: Chinese Academy of Sciences
Fangqing Zhao: Chinese Academy of Sciences

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Detection and quantification of circular RNAs (circRNAs) face several significant challenges, including high false discovery rate, uneven rRNA depletion and RNase R treatment efficiency, and underestimation of back-spliced junction reads. Here, we propose a novel algorithm, CIRIquant, for accurate circRNA quantification and differential expression analysis. By constructing pseudo-circular reference for re-alignment of RNA-seq reads and employing sophisticated statistical models to correct RNase R treatment biases, CIRIquant can provide more accurate expression values for circRNAs with significantly reduced false discovery rate. We further develop a one-stop differential expression analysis pipeline implementing two independent measures, which helps unveil the regulation of competitive splicing between circRNAs and their linear counterparts. We apply CIRIquant to RNA-seq datasets of hepatocellular carcinoma, and characterize two important groups of linear-circular switching and circular transcript usage switching events, which demonstrate the promising ability to explore extensive transcriptomic changes in liver tumorigenesis.

Date: 2020
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DOI: 10.1038/s41467-019-13840-9

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