A comprehensive pipeline for accurate annotation and quantification of circRNAs

ABSTRACT Identification and quantification of circular RNAs (circRNAs) depends strongly on the utilized computational pipeline. Here we describe an integrative approach for accurate annotation and quantification of circRNAs. First, we utilize several circRNA-identification pipelines to annotate circRNAs in a given organism. Second, we build a short sequence index that is used to search the unaligned RNA-seq reads. Our approach allows full annotation of circRNAs with fewer false positives and negatives than any individual pipeline or combination of them. Moreover, our approach is more sensitive than any individual pipeline and allows more accurate quantification and larger number of differentially expressed circRNAs.