{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:51:49Z","timestamp":1790661109716,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01CA262090"],"award-info":[{"award-number":["R01CA262090"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01CA243793"],"award-info":[{"award-number":["R01CA243793"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 CA272142"],"award-info":[{"award-number":["R01 CA272142"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P01CA214091"],"award-info":[{"award-number":["P01CA214091"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-20-1-0517"],"award-info":[{"award-number":["W81XWH-20-1-0517"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-16-1-0317"],"award-info":[{"award-number":["W81XWH-16-1-0317"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-16-1-0318"],"award-info":[{"award-number":["W81XWH-16-1-0318"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005189","name":"Leukemia & Lymphoma Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005189","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>As a fundamental aspect of normal cell signaling and disease states, there is great interest in determining alternative splicing (AS) changes in physiologic, pathologic, and pharmacologic settings. High throughput RNA sequencing and specialized software to detect AS has greatly enhanced our ability to determine transcriptome-wide splicing changes. Despite the richness of this data, deriving meaning from sometimes thousands of AS events is a substantial bottleneck for most investigators. We present SpliceTools, a suite of data processing modules that arms investigators with the ability to quickly produce summary statistics, mechanistic insights, and functional significance of AS changes through command line or through an online user interface. Utilizing RNA-seq datasets for 186 RNA binding protein knockdowns, nonsense mediated RNA decay inhibition, and pharmacologic splicing inhibition, we illustrate the utility of SpliceTools to distinguish splicing disruption from regulated transcript isoform changes, we show the broad transcriptome footprint of the pharmacologic splicing inhibitor, indisulam, we illustrate the utility in uncovering mechanistic underpinnings of splicing inhibition, we identify predicted neo-epitopes in pharmacologic splicing inhibition, and we show the impact of splicing alterations induced by indisulam on cell cycle progression. Together, SpliceTools puts rapid and easy downstream analysis at the fingertips of any investigator studying AS.<\/jats:p>","DOI":"10.1093\/nar\/gkad111","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T01:44:33Z","timestamp":1677807873000},"page":"e42-e42","source":"Crossref","is-referenced-by-count":27,"title":["SpliceTools, a suite of downstream RNA splicing analysis tools to investigate mechanisms and impact of alternative splicing"],"prefix":"10.1093","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0513-5281","authenticated-orcid":false,"given":"Erik K","family":"Flemington","sequence":"first","affiliation":[{"name":"Department of Pathology, Tulane University , New Orleans ,\u00a0LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel A","family":"Flemington","sequence":"additional","affiliation":[{"name":"Tulane Cancer Center, Tulane University , New Orleans ,\u00a0LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-0293","authenticated-orcid":false,"given":"Tina M","family":"O\u2019Grady","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tulane University , New Orleans ,\u00a0LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melody","family":"Baddoo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tulane University , New Orleans ,\u00a0LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trang","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tulane University , New Orleans ,\u00a0LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1622-5354","authenticated-orcid":false,"given":"Yan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Structural and Cellular Biology, Tulane University , New Orleans ,\u00a0LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan\u00a0A","family":"Ungerleider","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tulane University , New Orleans ,\u00a0LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"2023042403121381600_B1","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1101\/gad.316984.118","article-title":"TCF3 alternative splicing controlled by hnRNP H\/F regulates E-cadherin expression and hESC pluripotency","volume":"32","author":"Yamazaki","year":"2018","journal-title":"Genes Dev."},{"key":"2023042403121381600_B2","doi-asserted-by":"crossref","first-page":"e0184009","DOI":"10.1371\/journal.pone.0184009","article-title":"Cas9\/gRNA targeted excision of cystic fibrosis-causing deep-intronic splicing mutations restores normal splicing of CFTR mRNA","volume":"12","author":"Sanz","year":"2017","journal-title":"PLoS One"},{"key":"2023042403121381600_B3","doi-asserted-by":"crossref","first-page":"e88","DOI":"10.1136\/jmg.40.7.e88","article-title":"Transcript analysis of the cystic fibrosis splicing mutation 1525-1G&gt;A shows use of multiple alternative splicing sites and suggests a putative role of exonic splicing enhancers","volume":"40","author":"Ramalho","year":"2003","journal-title":"J. Med. Genet."},{"key":"2023042403121381600_B4","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1136\/jmg.2008.061259","article-title":"In vitro splicing analysis showed that availability of a cryptic splice site is not a determinant for alternative splicing patterns caused by +1G\u2192A mutations in introns of the dystrophin gene","volume":"46","author":"Habara","year":"2009","journal-title":"J. Med. Genet."},{"key":"2023042403121381600_B5","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nature10496","article-title":"Frequent pathway mutations of splicing machinery in myelodysplasia","volume":"478","author":"Yoshida","year":"2011","journal-title":"Nature"},{"key":"2023042403121381600_B6","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nature12634","article-title":"Mutational landscape and significance across 12 major cancer types","volume":"502","author":"Kandoth","year":"2013","journal-title":"Nature"},{"key":"2023042403121381600_B7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/ng.1032","article-title":"Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia","volume":"44","author":"Quesada","year":"2011","journal-title":"Nat. Genet."},{"key":"2023042403121381600_B8","doi-asserted-by":"crossref","first-page":"4032","DOI":"10.1016\/j.cell.2021.05.038","article-title":"Pharmacologic modulation of RNA splicing enhances anti-tumor immunity","volume":"184","author":"Lu","year":"2021","journal-title":"Cell"},{"key":"2023042403121381600_B9","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ccell.2019.07.003","article-title":"Therapeutic Targeting of RNA Splicing Catalysis through Inhibition of Protein Arginine Methylation","volume":"36","author":"Fong","year":"2019","journal-title":"Cancer Cell"},{"key":"2023042403121381600_B10","doi-asserted-by":"crossref","first-page":"E5593","DOI":"10.1073\/pnas.1419161111","article-title":"rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data","volume":"111","author":"Shen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2023042403121381600_B11","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/978-1-62703-514-9_10","article-title":"Identifying differential alternative splicing events from RNA sequencing data using RNASeq-MATS","volume":"1038","author":"Park","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"2023042403121381600_B12","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1093\/nar\/gkr1291","article-title":"MATS: a Bayesian framework for flexible detection of differential alternative splicing from RNA-Seq data","volume":"40","author":"Shen","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2023042403121381600_B13","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/nmeth.1528","article-title":"Analysis and design of RNA sequencing experiments for identifying isoform regulation","volume":"7","author":"Katz","year":"2010","journal-title":"Nat. Methods"},{"key":"2023042403121381600_B14","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13059-018-1417-1","article-title":"SUPPA2: fast, accurate, and uncertainty-aware differential splicing analysis across multiple conditions","volume":"19","author":"Trincado","year":"2018","journal-title":"Genome Biol."},{"key":"2023042403121381600_B15","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/s41586-020-2077-3","article-title":"A large-scale binding and functional map of human RNA-binding proteins","volume":"583","author":"Van\u00a0Nostrand","year":"2020","journal-title":"Nature"},{"key":"2023042403121381600_B16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2023042403121381600_B17","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"2023042403121381600_B18","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2023042403121381600_B19","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1261\/rna.059055.116","article-title":"Transcriptome-wide identification of NMD-targeted human mRNAs reveals extensive redundancy between SMG6- and SMG7-mediated degradation pathways","volume":"23","author":"Colombo","year":"2017","journal-title":"RNA"},{"key":"2023042403121381600_B20","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/nchembio.2363","article-title":"Selective degradation of splicing factor CAPERalpha by anticancer sulfonamides","volume":"13","author":"Uehara","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"2023042403121381600_B21","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1016\/j.celrep.2019.09.079","article-title":"Aryl sulfonamides degrade RBM39 and RBM23 by recruitment to CRL4-DCAF15","volume":"29","author":"Ting","year":"2019","journal-title":"Cell Rep."},{"key":"2023042403121381600_B22","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1021\/acschembio.5b00839","article-title":"A potent, selective, and cell-active inhibitor of human type I protein arginine methyltransferases","volume":"11","author":"Eram","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"2023042403121381600_B23","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1128\/MCB.00019-16","article-title":"Determination of a comprehensive alternative splicing regulatory network and combinatorial regulation by key factors during the epithelial-to-mesenchymal transition","volume":"36","author":"Yang","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"2023042403121381600_B24","doi-asserted-by":"crossref","first-page":"1060114","DOI":"10.3389\/fimmu.2022.1060114","article-title":"Reversal of splicing infidelity is a pre-activation step in B cell differentiation","volume":"13","author":"O\u2019Grady","year":"2022","journal-title":"Front Immunol."},{"key":"2023042403121381600_B25","doi-asserted-by":"crossref","first-page":"6336","DOI":"10.1126\/science.aal3755","article-title":"Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15","volume":"356","author":"Han","year":"2017","journal-title":"Science"},{"key":"2023042403121381600_B26","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1089\/1066527041410418","article-title":"Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals","volume":"11","author":"Yeo","year":"2004","journal-title":"J. Comput. Biol."},{"key":"2023042403121381600_B27","doi-asserted-by":"crossref","first-page":"D265","DOI":"10.1093\/nar\/gkz991","article-title":"CDD\/SPARCLE: the conserved domain database in 2020","volume":"48","author":"Lu","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2023042403121381600_B28","doi-asserted-by":"crossref","first-page":"5599","DOI":"10.1021\/acs.jmedchem.5b00627","article-title":"Optimization of a series of triazole containing mammalian target of rapamycin (mTOR) kinase inhibitors and the discovery of CC-115","volume":"58","author":"Mortensen","year":"2015","journal-title":"J. Med. Chem."},{"key":"2023042403121381600_B29","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1182\/blood-2016-02-700328","article-title":"Dual TORK\/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia","volume":"128","author":"Thijssen","year":"2016","journal-title":"Blood"},{"key":"2023042403121381600_B30","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/1471-2105-14-128","article-title":"Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool","volume":"14","author":"Chen","year":"2013","journal-title":"BMC Bioinf."},{"key":"2023042403121381600_B31","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2023042403121381600_B32","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1002\/cpz1.90","article-title":"Gene Set Knowledge Discovery with Enrichr","volume":"1","author":"Xie","year":"2021","journal-title":"Curr Protoc"},{"key":"2023042403121381600_B33","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1186\/s12859-019-2865-7","article-title":"SpliceV: analysis and publication quality printing of linear and circular RNA splicing, expression and regulation","volume":"20","author":"Ungerleider","year":"2019","journal-title":"BMC Bioinf."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/51\/7\/e42\/49875289\/gkad111.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/51\/7\/e42\/49875289\/gkad111.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T23:12:59Z","timestamp":1682291579000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/51\/7\/e42\/7067943"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,2]]},"references-count":33,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,3,2]]},"published-print":{"date-parts":[[2023,4,24]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkad111","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,4,24]]},"published":{"date-parts":[[2023,3,2]]}}}