{"doi":"10.1101/303412","title":"Systematic evaluation of isoform function in literature reports of alternative splicing","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>Although most mammalian genes have multiple isoforms, an ongoing debate is whether these isoforms are all functional as well as the extent to which they increase the genome’s functional repertoire. To ground this debate in data, we established a curation framework for evaluating experimental evidence of functionally distinct splice isoforms (FDSIs) and analyzed splice isoform function for over 700 human and mouse genes. Despite our bias towards prominently studied genes, we found experimental evidence meeting the classical definition for functionally distinct isoforms for only ~5% of the curated genes. If we relax our criteria, the fraction of genes with support for FDSIs remains low (~13%). We provide evidence that this picture will not change substantially with further curation. Furthermore, many FDSIs did not trace to a specific isoform in Ensembl. Our work has implications for computational analyses of alternative splicing and should help shape research around the role of splicing on gene function from presuming large general effects to acknowledging the need for stronger experimental evidence.</jats:p>","journal":null,"year":null,"id":30797,"datarank":0.3431631948612058,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.05127667250290872,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.05127667250290872,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":6,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":166538,"name":"Sophia Ly","orcid":null,"position":1,"is_corresponding":false},{"id":166539,"name":"Minh Phan","orcid":null,"position":2,"is_corresponding":false},{"id":166540,"name":"Brandon Huntington","orcid":null,"position":3,"is_corresponding":false},{"id":166541,"name":"Ellie Hogan","orcid":null,"position":4,"is_corresponding":false},{"id":166542,"name":"Chao Chun Liu","orcid":null,"position":5,"is_corresponding":false},{"id":166543,"name":"James Liu","orcid":null,"position":6,"is_corresponding":false},{"id":166544,"name":"Paul Pavlidis","orcid":null,"position":7,"is_corresponding":false},{"id":166537,"name":"Shamsuddin A. Bhuiyan","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24523987","pmcid":null,"openalex_id":"https://openalex.org/W2797310082","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"5R01MH111099-13","title":"Neuroinformatics for gene expression: networks, function and meta-analysis"},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"unidentified","title":"unidentified"}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2021,"count":1},{"year":2022,"count":2},{"year":2024,"count":2}],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2018/05/13/303412.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2018/05/13/303412.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/303412","host_type":"publisher"},{"url":"https://doi.org/10.1101/303412","host_type":"repository"},{"url":"https://doi.org/10.1186/s12864-018-5013-2","host_type":""},{"url":"https://bmcgenomics.biomedcentral.com/track/pdf/10.1186/s12864-018-5013-2.pdf","host_type":""},{"url":"https://dx.doi.org/10.14288/1.0371623","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/30153812","host_type":""},{"url":"http://dx.doi.org/10.1186/s12864-018-5013-2","host_type":""},{"url":"https://doaj.org/article/60a97d9667b44fabbe964fa7046c74bd","host_type":""},{"url":"https://dx.doi.org/10.1101/303412","host_type":""},{"url":"https://dx.doi.org/10.1186/s12864-018-5013-2","host_type":""},{"url":"http://dx.doi.org/10.1101/303412","host_type":""},{"url":"https://doi.org/https://doi.org/10.1186/s12864-018-5013-2","host_type":""}],"fields_of_study":["RNA Research and Splicing","RNA modifications and cancer","RNA and protein synthesis mechanisms"],"mesh_terms":[],"keywords":["Gene isoform","Alternative splicing","Ensembl","Gene","Function (biology)","Computational biology","Biology","splice","RNA splicing","Genetics","Genome","Genomics","Isoform function","612","Functional diversity","QH426-470","Mice","Animals","Humans","Protein Isoforms","Literature curation","TP248.13-248.65","Biotechnology","Research Article"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T04:40:27.028271Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}