Accurate Assembly of Circular RNAs with TERRACE

Circular RNA (circRNA) is a class of RNA molecules that forms a closed loop with its 5’ and 3’ ends covalently bonded. CircRNAs were severely overlooked previously owing to the biases in the RNA-seq protocols and in the detection algorithms, but recently gained tremendous attentions in both aspects. Most existing methods for assembling circRNAs heavily rely on the annotated transcriptomes, and hence exhibit unsatisfactory accuracy when a high-quality annotation is unavailable. Here we present TERRACE, a new algorithm for full-length assembly of circRNAs from paired-end total RNA-seq data. TERRACE is compared with leading circRNA detection methods on both simulations and biological datasets. Our method consistently outperforms by a large margin in sensitivity while maintaining better or comparable precision. In particular, when the annotations are not provided, TERRACE can assemble 123%–412% more correct circRNAs than state-of-the-art methods on human tissues. TERRACE presents a major leap on assembling full-length circRNAs from RNA-seq data, and we expect it to be widely used in the downstream research on circRNAs. TERRACE is freely available at https://github.com/Shao-Group/TERRACE. The full version of this manuscript is available at https://doi.org/10.1101/2024.02.09.579380.