Comprehensive comparison of two types of algorithm for circRNA detection from short-read RNA-Seq

Circular RNA is generally formed by the 'back-splicing' process between the upstream splice acceptor and the downstream donor in/not in the regulation of the corresponding RNA-binding proteins or cis-elements. Therefore, more and more software packages have been developed and they are mostly based on the identification of the back-spliced junction reads. However, recent studies developed two software tools that can detect circRNA candidates by constructing k-mer table or/and de Bruijn graph rather than reads mapping.

Here, we compared the precision, sensitivity and detection efficiency between software tools based on different algorithms. Eleven representative detection tools with two types of algorithm were selected for the overall pipeline analysis of RNA-seq datasets with/without RNase R treatment in two cell lines. Precision, sensitivity, AUC, F1 score and detection efficiency metrics were assessed to compare the prediction tools. Meanwhile, the sensitivity and distribution of highly expressed circRNAs before and after RNase R treatment were also revealed by their enrichment, unaffected and depleted candidate frequencies. Eventually, we found that compared to the k-mer based tools, CIRI2 and KNIFE based on reads mapping had relatively superior and more balanced detection performance regardless of the cell line or RNase R (-/+) datasets.

All predicted results and source codes can be retrieved from https://github.com/luffy563/circRNA_tools_comparison.

Supplementary data are available at Bioinformatics online.