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bioRxiv · 10.1101/2025.04.06.647416

OmniSplice: a framework-free splicing event reporter

Lannes, R.·Fingerhut, J. M.·Yamashita, Y. M. M.
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Abstract

Splicing generates mature mRNA by removing introns from nascent transcripts and is widely studied using RNA sequencing. However, most RNA-seq analysis pipelines classify RNA-seq reads according to predefined splice-junction structures and discard those that do not conform to such predefined models, potentially obscuring biologically meaningful splicing events. In this study, we developed OmniSplice, a computational framework that captures and analyzes RNA-seq reads that overlap annotated exon ends without assuming predefined splicing architectures. This approach enables systematic detection of non-canonical splicing events that are often overlooked by conventional analyses. Applying OmniSplice to Drosophila splicing factor mutants and mouse TDP-43 mutant datasets, we found widespread splicing defects with non-canonical junctions that were not previously recognized, including back-splicing and trans-splicing. Together, these results demonstrate that RNA-seq datasets may contain a substantial reservoir of overlooked splicing information, warranting more comprehensive approaches for analyzing RNA-seq data for splicing events.

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Lannes, R., Fingerhut, J. M., Yamashita, Y. M. M.. 2025-04-08. OmniSplice: a framework-free splicing event reporter. https://doi.org/10.1101/2025.04.06.647416

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