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You are here: Home / Teams / Alternative splicing and tumoral progression - D. Auboeuf / Publications / Identification of protein features encoded by alternative exons using Exon Ontology.

Identification of protein features encoded by alternative exons using Exon Ontology.

Leon-Charles Tranchevent, Fabien Aube, Louis Dulaurier, Clara Benoit-Pilven, Amandine Rey, Arnaud Poret, Emilie Chautard, Hussein Mortada, Francois-Olivier Desmet, Fatima Z Chakrama, Maira A Moreno-Garcia, Evelyne Goillot, Stephane Janczarski, Franck Mortreux, Cyril F Bourgeois, and Didier Auboeuf (2017)

Genome Res, 27(6):1087-1097.

Transcriptomic genome-wide analyses demonstrate massive variation of alternativesplicing in many physiological and pathological situations. One major challenge is now to establish the biological contribution of alternative splicing variation in physiological- or pathological-associated cellular phenotypes. Toward this end, we developed a computational approach, named "Exon Ontology," based on terms corresponding to well-characterized protein features organized in an ontology tree. Exon Ontology is conceptually similar to Gene Ontology-based approaches but focuses on exon-encoded protein features instead of gene level functional annotations. Exon Ontology describes the protein features encoded by a selected list of exons and looks for potential Exon Ontology term enrichment. By applyingthis strategy to exons that are differentially spliced between epithelial and mesenchymal cells and after extensive experimental validation, we demonstrate that Exon Ontology provides support to discover specific protein features regulated by alternative splicing. We also show that Exon Ontology helps to unravel biological processes that depend on suites of coregulated alternative exons, as we uncovered a role of epithelial cell-enriched splicing factors in the AKT signaling pathway and of mesenchymal cell-enriched splicing factors in driving splicing events impacting on autophagy. Freely available on the web, Exon Ontology is the first computational resource that allows getting a quick insightinto the protein features encoded by alternative exons and investigating whethercoregulated exons contain the same biological information.

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