CYCLeR - a novel tool for the full isoform assembly and quantification of circRNAs

Abstract

Splicing is one key mechanism determining the state of any eukaryotic cell. Apart from linear splice variants, circular splice variants (circRNAs) can arise via non-canonical splicing involving a back-splice junction (BSJ). Most existing methods only identify circRNAs via the corresponding BSJ, but do not aim to estimate their full sequence identity or to identify different, alternatively spliced circular isoforms arising from the same BSJ. We here present CYCLO_SCPLOWEC_SCPLOWR, the first computational method for identifying the full sequence identify of new and alternatively spliced circRNAs and their abundances while simultaneously co-estimating the abundances of known linear splicing isoforms. We show that CYCLO_SCPLOWEC_SCPLOWR significantly out-performs existing methods in terms of sensitivity, precision and quantification of transcripts. When analysing D. melanogaster data, CYCLO_SCPLOWEC_SCPLOWR uncovers biological patterns of circRNA expression that other methods fail to observe.