{"doi":"10.1261/rna.048769.114","title":"Splicing predictions reliably classify different types of alternative splicing","abstract":"<jats:p>Alternative splicing is a key player in the creation of complex mammalian transcriptomes and its misregulation is associated with many human diseases. Multiple mRNA isoforms are generated from most human genes, a process mediated by the interplay of various RNA signature elements and<jats:italic>trans</jats:italic>-acting factors that guide spliceosomal assembly and intron removal. Here, we introduce a splicing predictor that evaluates hundreds of RNA features simultaneously to successfully differentiate between exons that are constitutively spliced, exons that undergo alternative 5′ or 3′ splice-site selection, and alternative cassette-type exons. Surprisingly, the splicing predictor did not feature strong discriminatory contributions from binding sites for known splicing regulators. Rather, the ability of an exon to be involved in one or multiple types of alternative splicing is dictated by its immediate sequence context, mainly driven by the identity of the exon's splice sites, the conservation around them, and its exon/intron architecture. Thus, the splicing behavior of human exons can be reliably predicted based on basic RNA sequence elements.</jats:p>","journal":"RNA","year":2015,"id":34879,"datarank":1.1474071845639409,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.6706991100117489,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.6706991100117489,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":20,"citers_with_citation_signal":17,"citers_with_endowment":17,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":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":171436,"name":"Klemens J. Hertel","orcid":null,"position":1,"is_corresponding":false},{"id":173045,"name":"Anke Busch","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25805853","pmcid":"PMC4408789","openalex_id":"https://openalex.org/W2115820057","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"R01 GM62287","title":null},{"funder_name":"National Institutes of Health","grant_id":"R01 CA177651","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM090056","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA062203","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM062287","title":null},{"funder_name":"National Institutes of Health","grant_id":"2R01GM062287-10","title":"Mechanisms of Enhancer Dependent Splice Site Activation"},{"funder_name":"National Institutes of Health","grant_id":"5R01CA177651-05","title":"Coordinated regulation of alternative pre-mRNA processing in colon cancer"},{"funder_name":"German Academic Exchange Service","grant_id":"","title":null}],"total_grants":8,"fwci":1.5057,"citation_percentile":0.82352603,"influential_citations":3,"citation_trend":[{"year":2015,"count":2},{"year":2016,"count":3},{"year":2017,"count":2},{"year":2018,"count":3},{"year":2019,"count":5},{"year":2021,"count":2},{"year":2022,"count":1},{"year":2023,"count":3},{"year":2024,"count":1},{"year":2025,"count":1}],"oa_status":"bronze","license":"CC BY","oa_locations":[{"url":"http://rnajournal.cshlp.org/content/21/5/813.full.pdf","host_type":"journal"},{"url":"http://rnajournal.cshlp.org/content/21/5/813.full.pdf","host_type":"BRONZE"},{"url":"http://rnajournal.cshlp.org/content/21/5/813.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1261/rna.048769.114","host_type":"publisher"},{"url":"https://doi.org/10.1261/rna.048769.114","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25805853","host_type":"repository"},{"url":"https://escholarship.org/uc/item/9fj3d1n4","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4408789","host_type":"repository"},{"url":"http://www.escholarship.org/uc/item/9fj3d1n4","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4408789","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4408789?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1261/rna.048769.114","host_type":""},{"url":"https://dx.doi.org/10.1261/rna.048769.114","host_type":""},{"url":"https://escholarship.org/content/qt9fj3d1n4/qt9fj3d1n4.pdf","host_type":""},{"url":"https://doi.org/https://doi.org/10.1261/rna.048769.114","host_type":""}],"fields_of_study":["RNA Research and Splicing","RNA and protein synthesis mechanisms","RNA modifications and cancer","Biology","Medicine","Computer Science","0301 basic medicine","03 medical and health sciences","0303 health sciences","Alternative Splicing","Animals","Computational Biology","Exons","Genetic Code","Humans","Mammals","RNA Splice Sites","Reproducibility of Results","Sequence Analysis, RNA"],"mesh_terms":["Animals","Exons","Genetic Code","Humans","Mammals","Reproducibility of Results","Alternative Splicing","Sequence Analysis, RNA","Computational Biology","RNA Splice Sites"],"keywords":["Exon","RNA splicing","Alternative splicing","Biology","Intron","Exonic splicing enhancer","Splice site mutation","Minigene","Genetics","Computational biology","Exon skipping","Context (archaeology)","splice","RNA","Gene","Bioinformatics","Support vector machine","Splicing Predictor","570","1.1 Normal biological development and functioning","Bioinformatics and Computational Biology","610","Animals","Humans","Mammals","Sequence Analysis, RNA","Human Genome","Reproducibility of Results","Exons","Biological Sciences","Genetic Code","Biochemistry and cell biology","RNA Splice Sites","Sequence Analysis","Developmental Biology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Reduced inequalities"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T20:50:08.366601Z","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":[]}