{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T09:42:22Z","timestamp":1792575742385,"version":"4.5.0"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 LM013437"],"award-info":[{"award-number":["R01 LM013437"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"NIH\/NICHD","doi-asserted-by":"publisher","award":["F30HD098803"],"award-info":[{"award-number":["F30HD098803"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH\/NHGRI","award":["T32HG009495"],"award-info":[{"award-number":["T32HG009495"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>RNA splicing plays important roles in cell-type-specific expression of gene isoforms and is causally linked to numerous diseases. Previously, our group developed Modeling Alternative Junction Inclusion Quantification (MAJIQ) V1 and V2 for RNA splicing detection, quantification, and visualization from RNA sequencing. Here we report an update, MAJIQ V3, that offers critical new functionality together with faster and more accurate quantification algorithms. MAJIQ V3 enables users to combine splicegraphs, quantify splicing from an RNA-seq experiment with respect to a splicegraph, and compare one splicegraph to another, enabling new patterns of performant RNA splicing analyses from RNA-seq. MAJIQ V3 utilizes a new probabilistic model for detecting intron retention, correcting a bias that resulted from previous heuristics. MAJIQ V3 benefits from a full re-implementation utilizing more performant I\/O patterns, data structures, and algorithms. We demonstrate the benefits of MAJIQ V3 using GTEx and LRGASP data for different analysis scenarios involving different dataset sizes.<\/jats:p>","DOI":"10.1093\/nargab\/lqag126","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T09:04:44Z","timestamp":1792573484000},"source":"Crossref","is-referenced-by-count":0,"title":["MAJIQ V3: Scalable and accurate RNA splicing analysis with splicegraph algebra and improved intron retention modeling"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8850-6070","authenticated-orcid":false,"given":"Joseph K","family":"Aicher","sequence":"first","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1539-2591","authenticated-orcid":false,"given":"Barry","family":"Slaff","sequence":"additional","affiliation":[{"name":"Department of Computer and Information Science, School of Engineering, University of Pennsylvania , Philadelphia, 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6494-8015","authenticated-orcid":false,"given":"San","family":"Jewell","sequence":"additional","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7710-4551","authenticated-orcid":false,"given":"Matthew R","family":"Gazzara","sequence":"additional","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5748-3507","authenticated-orcid":false,"given":"Elizabeth\u00a0J K","family":"Bhoj","sequence":"additional","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, 19104 ,","place":["United States"]},{"name":"Division of Human Genetics, Children\u2019s Hospital of Philadelphia , Philadelphia, 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3005-5048","authenticated-orcid":false,"given":"Yoseph","family":"Barash","sequence":"additional","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, 19104 ,","place":["United States"]},{"name":"Department of Computer and Information Science, School of Engineering, University of Pennsylvania , Philadelphia, 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"2026102105043912300_B1","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1038\/ng.259","article-title":"Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing","volume":"40","author":"Pan","year":"2008","journal-title":"Nat Genet"},{"key":"2026102105043912300_B2","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1038\/nature07509","article-title":"Alternative isoform regulation in human tissue transcriptomes","volume":"456","author":"Wang","year":"2008","journal-title":"Nature"},{"key":"2026102105043912300_B3","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/nrg.2015.3","article-title":"RNA mis-splicing in disease","volume":"17","author":"Scotti","year":"2016","journal-title":"Nat Rev Genet"},{"key":"2026102105043912300_B4","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1042\/CS20160211","article-title":"RNA splicing in human disease and in the clinic","volume":"131","author":"Baralle","year":"2017","journal-title":"Clin Sci (Colch)"},{"key":"2026102105043912300_B5","doi-asserted-by":"publisher","first-page":"bbad121","DOI":"10.1093\/bib\/bbad121","article-title":"A comprehensive benchmarking of differential splicing tools for RNA-seq analysis at the event level","volume":"24","author":"Jiang","year":"2023","journal-title":"Brief Bioinform"},{"key":"2026102105043912300_B6","doi-asserted-by":"publisher","first-page":"e11752","DOI":"10.7554\/eLife.11752","article-title":"A new view of transcriptome complexity and regulation through the lens of local splicing variations","volume":"5","author":"Vaquero-Garcia","year":"2016","journal-title":"eLife"},{"key":"2026102105043912300_B7","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1038\/s41467-023-36585-y","article-title":"RNA splicing analysis using heterogeneous and large RNA-seq datasets","volume":"14","author":"Vaquero-Garcia","year":"2023","journal-title":"Nat Commun"},{"key":"2026102105043912300_B8","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1101\/gr.278659.123","article-title":"Contrasting and combining transcriptome complexity captured by short and long RNA sequencing reads","volume":"34","author":"Han","year":"2024","journal-title":"Genome Res"},{"key":"2026102105043912300_B9","doi-asserted-by":"publisher","first-page":"3353","DOI":"10.1038\/s41467-021-23608-9","article-title":"MOCCASIN: a method for correcting for known and unknown confounders in RNA splicing analysis","volume":"12","author":"Slaff","year":"2021","journal-title":"Nat Commun"},{"key":"2026102105043912300_B10","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The Genotype-Tissue Expression (GTEx) project","volume":"45","author":"Lonsdale","year":"2013","journal-title":"Nat Genet"},{"key":"2026102105043912300_B11","doi-asserted-by":"publisher","first-page":"102628","DOI":"10.1016\/j.gim.2026.102628","article-title":"MAJIQ-CLIN: a novel tool to help identify Mendelian disease-causing variants from RNA-seq data","volume":"28","author":"Aicher","year":"2026","journal-title":"Genet Med"},{"key":"2026102105043912300_B12","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1038\/s41592-024-02298-3","article-title":"Systematic assessment of long-read RNA-seq methods for transcript identification and quantification","volume":"21","author":"Pardo-Palacios","year":"2024","journal-title":"Nat Methods"},{"key":"2026102105043912300_B13","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/s41587-022-01565-y","article-title":"Accurate isoform discovery with IsoQuant using long reads","volume":"41","author":"Prjibelski","year":"2023","journal-title":"Nat Biotechnol"},{"key":"2026102105043912300_B14","doi-asserted-by":"publisher","first-page":"986","DOI":"10.3390\/genes16080986","article-title":"Intron retention: a reemerging paradigm in RNA biology and post-transcriptional gene regulation","volume":"16","author":"Porras-Tobias","year":"2025","journal-title":"Genes"}],"container-title":["NAR Genomics and Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nargab\/article-pdf\/8\/4\/lqag126\/72219625\/lqag126.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nargab\/article-pdf\/8\/4\/lqag126\/72219625\/lqag126.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T09:04:45Z","timestamp":1792573485000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nargab\/article\/doi\/10.1093\/nargab\/lqag126\/8960101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":14,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,9,28]]}},"URL":"https:\/\/doi.org\/10.1093\/nargab\/lqag126","relation":{},"ISSN":["2631-9268"],"issn-type":[{"value":"2631-9268","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,12]]},"published":{"date-parts":[[2026,9,28]]},"article-number":"lqag126"}}