2026-07-22T01:50:12Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/198752024-09-27T09:16:40Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Pozo, Fernando author Martinez-Gomez, Laura author Walsh, Thomas A author Rodriguez, José Manuel author Di Domenico, Tomas author Abascal, Federico author Vazquez, Jesus author Tress, Michael L author 2021-06 Alternative splicing of messenger RNA can generate an array of mature transcripts, but it is not clear how many go on to produce functionally relevant protein isoforms. There is only limited evidence for alternative proteins in proteomics analyses and data from population genetic variation studies indicate that most alternative exons are evolving neutrally. Determining which transcripts produce biologically important isoforms is key to understanding isoform function and to interpreting the real impact of somatic mutations and germline variations. Here we have developed a method, TRIFID, to classify the functional importance of splice isoforms. TRIFID was trained on isoforms detected in large-scale proteomics analyses and distinguishes these biologically important splice isoforms with high confidence. Isoforms predicted as functionally important by the algorithm had measurable cross species conservation and significantly fewer broken functional domains. Additionally, exons that code for these functionally important protein isoforms are under purifying selection, while exons from low scoring transcripts largely appear to be evolving neutrally. TRIFID has been developed for the human genome, but it could in principle be applied to other well-annotated species. We believe that this method will generate valuable insights into the cellular importance of alternative splicing. NAR Genom Bioinform. 2021 May 22;3(2):lqab044. 10.1093/nargab/lqab044 2631-9268 NAR genomics and bioinformatics 34046593 http://hdl.handle.net/20.500.12105/19875 Assessing the functional relevance of splice isoforms.