{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T01:34:35Z","timestamp":1770687275710,"version":"3.49.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005946","name":"Jackson Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005946","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>Advances in RNA sequencing technologies have achieved an unprecedented accuracy in the quantification of mRNA isoforms, but our knowledge of isoform-specific functions has lagged behind. There is a need to understand the functional consequences of differential splicing, which could be supported by the generation of accurate and comprehensive isoform-specific gene ontology annotations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We present isoform interpretation, a method that uses expectation\u2013maximization to infer isoform-specific functions based on the relationship between sequence and functional isoform similarity. We predicted isoform-specific functional annotations for 85\u00a0617 isoforms of 17\u00a0900 protein-coding human genes spanning a range of 17\u00a0430 distinct gene ontology terms. Comparison with a gold-standard corpus of manually annotated human isoform functions showed that isoform interpretation significantly outperforms state-of-the-art competing methods. We provide experimental evidence that functionally related isoforms predicted by isoform interpretation show a higher degree of domain sharing and expression correlation than functionally related genes. We also show that isoform sequence similarity correlates better with inferred isoform function than with gene-level function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>Source code, documentation, and resource files are freely available under a GNU3 license at https:\/\/github.com\/TheJacksonLaboratory\/isopretEM and https:\/\/zenodo.org\/record\/7594321.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btad132","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T14:17:33Z","timestamp":1679062653000},"source":"Crossref","is-referenced-by-count":6,"title":["An expectation\u2013maximization framework for comprehensive prediction of isoform-specific functions"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1653-8206","authenticated-orcid":false,"given":"Guy","family":"Karlebach","sequence":"first","affiliation":[{"name":"The Jackson Laboratory for Genomic 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