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 ( circRNA s) can arise via non-canonical splicing involving a back-splice junction (BSJ). Most existing methods only identify circRNA s 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 CYCL e R, the first computational method for identifying the full sequence identify of new and alternatively spliced circRNA s and their abundances while simultaneously co-estimating the abundances of known linear splicing isoforms. We show that CYCL e R significantly out-performs existing methods in terms of sensitivity, precision and quantification of transcripts. When analysing D. melanogaster data, CYCL e R uncovers biological patterns of circRNA expression that other methods fail to observe.