{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:22:31Z","timestamp":1791148951031,"version":"4.1.0"},"reference-count":124,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002347","name":"bundesministerium f\u00fcr bildung und forschung","doi-asserted-by":"publisher","award":["01zx1908a"],"award-info":[{"award-number":["01zx1908a"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universit\u00e4t Hamburg (1037);"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genome Biol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alternative splicing (AS) is an important aspect of gene regulation. Nevertheless, its role in molecular processes and pathobiology is far from understood. A roadblock is that tools for the functional analysis of AS-set events are lacking. To mitigate this, we developed NEASE, a tool integrating pathways with structural annotations of protein-protein interactions to functionally characterize AS events. We show in four application cases how NEASE can identify pathways contributing to tissue identity and cell type development, and how it highlights splicing-related biomarkers. With a unique view on AS, NEASE generates unique and meaningful biological insights complementary to classical pathways analysis.<\/jats:p>","DOI":"10.1186\/s13059-021-02538-1","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T04:02:38Z","timestamp":1638417758000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Functional enrichment of alternative splicing events with NEASE reveals insights into tissue identity and diseases"],"prefix":"10.1186","volume":"22","author":[{"given":"Zakaria","family":"Louadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"Elkjaer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Klug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chit Tong","family":"Lio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Fenn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"Illes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Bongiovanni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Baumbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Kacprowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"List","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7592-2080","authenticated-orcid":false,"given":"Olga","family":"Tsoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"2538_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.gene.2004.10.022","volume":"344","author":"S Stamm","year":"2005","unstructured":"Stamm S, Ben-Ari S, Rafalska I, Tang Y, Zhang Z, Toiber D, et al. Function of alternative splicing. Gene. 2005;344:1\u201320. https:\/\/doi.org\/10.1016\/j.gene.2004.10.022.","journal-title":"Gene"},{"issue":"10","key":"2538_CR2","doi-asserted-by":"publisher","first-page":"R74","DOI":"10.1186\/gb-2004-5-10-r74","volume":"5","author":"G Yeo","year":"2004","unstructured":"Yeo G, Holste D, Kreiman G, Burge CB. Variation in alternative splicing across human tissues. Genome Biol. 2004;5(10):R74. https:\/\/doi.org\/10.1186\/gb-2004-5-10-r74.","journal-title":"Genome Biol"},{"key":"2538_CR3","doi-asserted-by":"publisher","unstructured":"Baralle F, Giudice J. Alternative splicing as a regulator of development and tissue identity. Nat Rev Mol Cell Biol. 2017;18(7) Available from:. https:\/\/doi.org\/10.1038\/nrm.2017.27.","DOI":"10.1038\/nrm.2017.27"},{"issue":"4","key":"2538_CR4","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1007\/s12551-018-0439-y","volume":"10","author":"A Beqqali","year":"2018","unstructured":"Beqqali A. Alternative splicing in cardiomyopathy. Biophys Rev. 2018;10(4):1061\u201371.","journal-title":"Biophys Rev"},{"key":"2538_CR5","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.mcn.2013.04.005","volume":"56","author":"AGL Douglas","year":"2013","unstructured":"Douglas AGL, Wood MJA. Splicing therapy for neuromuscular disease. Mol Cell Neurosci. 2013;56:169\u201385. https:\/\/doi.org\/10.1016\/j.mcn.2013.04.005.","journal-title":"Mol Cell Neurosci"},{"key":"2538_CR6","doi-asserted-by":"publisher","unstructured":"\u200b\u200bEvsyukova I, Somarelli JA, Gregory SG, Garcia-Blanco MA. Alternative splicing in multiple sclerosis and other 673 autoimmune diseases. RNA Biology. 2010;7(4)462\u201373. https:\/\/doi.org\/10.4161\/rna.7.4.12301.","DOI":"10.4161\/rna.7.4.12301"},{"issue":"9","key":"2538_CR7","doi-asserted-by":"publisher","first-page":"1900","DOI":"10.1016\/j.febslet.2005.02.047","volume":"579","author":"N L\u00f3pez-Bigas","year":"2005","unstructured":"L\u00f3pez-Bigas N, Audit B, Ouzounis C, Parra G, Guig\u00f3 R. Are splicing mutations the most frequent cause of hereditary disease? FEBS Lett. 2005;579(9):1900\u20133. https:\/\/doi.org\/10.1016\/j.febslet.2005.02.047.","journal-title":"FEBS Lett"},{"key":"2538_CR8","doi-asserted-by":"publisher","unstructured":"Karlebach G, Veiga DFT, Mays AD, Chatzipantsiou C, Barja PP, Chatzou M, et al. The impact of biological sex on alternative splicing. bioRxiv. 2020:490904. https:\/\/doi.org\/10.1101\/490904.","DOI":"10.1101\/490904"},{"issue":"10","key":"2538_CR9","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.1101\/gr.122226.111","volume":"21","author":"JR Tollervey","year":"2011","unstructured":"Tollervey JR, Wang Z, Hortob\u00e1gyi T, Witten JT, Zarnack K, Kayikci M, et al. Analysis of alternative splicing associated with aging and neurodegeneration in the human brain. Genome Res. 2011;21(10):1572\u201382. https:\/\/doi.org\/10.1101\/gr.122226.111.","journal-title":"Genome Res"},{"issue":"1","key":"2538_CR10","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/s13059-017-1286-z","volume":"18","author":"M Heinig","year":"2017","unstructured":"Heinig M, Adriaens ME, Schafer S, van Deutekom HWM, Lodder EM, Ware JS, et al. Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy. Genome Biol. 2017;18(1):170. https:\/\/doi.org\/10.1186\/s13059-017-1286-z.","journal-title":"Genome Biol"},{"issue":"2","key":"2538_CR11","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.tibs.2016.08.008","volume":"42","author":"ML Tress","year":"2017","unstructured":"Tress ML, Abascal F, Valencia A. Alternative Splicing May Not Be the Key to Proteome Complexity. Trends Biochem Sci. Elsevier Ltd. 2017;42(2):98\u2013110. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/27712956\/. https:\/\/doi.org\/10.1016\/j.tibs.2016.08.008.","journal-title":"Trends Biochem Sci. Elsevier Ltd"},{"issue":"14","key":"2538_CR12","doi-asserted-by":"publisher","first-page":"4873","DOI":"10.1093\/nar\/gkp471","volume":"37","author":"E Melamud","year":"2009","unstructured":"Melamud E, Moult J. Stochastic noise in splicing machinery. Nucleic Acids Res. 2009;37(14):4873\u201386. https:\/\/doi.org\/10.1093\/nar\/gkp471.","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"2538_CR13","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.cell.2016.01.029","volume":"164","author":"X Yang","year":"2016","unstructured":"Yang X, Coulombe-Huntington J, Kang S, Sheynkman GM, Hao T, Richardson A, et al. Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell. 2016;164(4):805\u201317. https:\/\/doi.org\/10.1016\/j.cell.2016.01.029.","journal-title":"Cell"},{"issue":"6","key":"2538_CR14","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.molcel.2012.05.039","volume":"46","author":"M Buljan","year":"2012","unstructured":"Buljan M, Chalancon G, Eustermann S, Wagner GP, Fuxreiter M, Bateman A, et al. Tissue-specific splicing of disordered segments that embed binding motifs rewires protein interaction networks. Mol Cell. 2012;46(6):871\u201383.","journal-title":"Mol Cell"},{"issue":"Pt B","key":"2538_CR15","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.biocel.2017.07.013","volume":"91","author":"PJ da Costa","year":"2017","unstructured":"da Costa PJ, Menezes J, Rom\u00e3o L. The role of alternative splicing coupled to nonsense-mediated mRNA decay in human disease. Int J Biochem Cell Biol. 2017;91(Pt B):168\u201375.","journal-title":"Int J Biochem Cell Biol"},{"key":"2538_CR16","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-16-0459","volume-title":"Sandelin A","author":"V-S Kristoffer","year":"2017","unstructured":"Kristoffer V-S. Sandelin A. Genomics: The Landscape of Isoform Switches in Human Cancers; 2017; Available from:. https:\/\/doi.org\/10.1158\/1541-7786.MCR-16-0459."},{"key":"2538_CR17","doi-asserted-by":"publisher","unstructured":"delafuente L, Arzalluz-luque \u00c1, Tard\u00e1guila M, Delrisco H, Mart\u00ed C, Tarazona S, et al. tappAS: a comprehensive computational framework for the analysis of the functional impact of differential splicing. Genome Biol. 2020;21(1) Available from:. https:\/\/doi.org\/10.1186\/s13059-020-02028-w.","DOI":"10.1186\/s13059-020-02028-w"},{"issue":"W1","key":"2538_CR18","doi-asserted-by":"publisher","first-page":"W162","DOI":"10.1093\/nar\/gkab357","volume":"49","author":"ST Gal-Oz","year":"2021","unstructured":"Gal-Oz ST, Haiat N, Eliyahu D, Shani G, Shay T. DoChaP: the domain change presenter. Nucleic Acids Res. 2021;49(W1):W162\u20138. https:\/\/doi.org\/10.1093\/nar\/gkab357.","journal-title":"Nucleic Acids Res"},{"key":"2538_CR19","doi-asserted-by":"publisher","first-page":"2215","DOI":"10.1016\/j.celrep.2017.08.012","volume":"20","author":"H Ctor Climente-Gonz\u00e1 Lez","year":"2017","unstructured":"Ctor Climente-Gonz\u00e1 Lez H, Porta-Pardo E, Godzik A, Correspondence EE, Eyras E. The Functional Impact of Alternative Splicing in Cancer. Cell Rep. 2017;20:2215\u201326.","journal-title":"Cell Rep"},{"issue":"6","key":"2538_CR20","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1101\/gr.212696.116","volume":"27","author":"L-C Tranchevent","year":"2017","unstructured":"Tranchevent L-C, Aub\u00e9 F, Dulaurier L, Benoit-Pilven C, Rey A, Poret A, et al. Identification of protein features encoded by alternative exons using Exon Ontology. Genome Res. 2017;27(6):1087\u201397.","journal-title":"Genome Res"},{"key":"2538_CR21","doi-asserted-by":"publisher","unstructured":"Louadi Z, Yuan K, Gress A, Tsoy O, Kalinina OV, Baumbach J, et al. DIGGER: exploring the functional role of alternative 709 splicing in protein interactions. Nucleic Acids Res. 2020;49(D1):D309-D318. https:\/\/doi.org\/10.1093\/nar\/gkaa768.","DOI":"10.1093\/nar\/gkaa768"},{"key":"2538_CR22","doi-asserted-by":"publisher","unstructured":"Kumar M, Gouw M, Michael S. Amano-S \u00b4 Anchez HS\u00b4, Pancsa R, Glavina J, et al. ELM-the eukaryotic linear motif resource in 2020. Nucleic Acids Res. 2020;48. Available from: https:\/\/academic.oup.com\/nar\/article\/48\/D1\/D296\/5611669. https:\/\/doi.org\/10.1093\/nar\/gkz1030.","DOI":"10.1093\/nar\/gkz1030"},{"issue":"D1","key":"2538_CR23","doi-asserted-by":"publisher","first-page":"D427","DOI":"10.1093\/nar\/gky995","volume":"47","author":"S El-Gebali","year":"2019","unstructured":"El-Gebali S, Mistry J, Bateman A, Eddy SR, Luciani A, Potter SC, et al. The Pfam protein families database in 2019. Nucleic Acids Res. 2019;47(D1):D427\u201332. https:\/\/doi.org\/10.1093\/nar\/gky995.","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"2538_CR24","doi-asserted-by":"publisher","first-page":"D529","DOI":"10.1093\/nar\/gky1079","volume":"47","author":"R Oughtred","year":"2019","unstructured":"Oughtred R, Stark C, Breitkreutz B-J, Rust J, Boucher L, Chang C, et al. The BioGRID interaction database: 2019 update. Nucleic Acids Res. 2019;47(D1):D529\u201341. https:\/\/doi.org\/10.1093\/nar\/gky1079.","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"2538_CR25","doi-asserted-by":"publisher","first-page":"D730","DOI":"10.1093\/nar\/gkq1229","volume":"39","author":"S Yellaboina","year":"2011","unstructured":"Yellaboina S, Tasneem A, Zaykin DV, Raghavachari B, Jothi R. DOMINE: a comprehensive collection of known and predicted domain-domain interactions. Nucleic Acids Res. 2011;39(Database issue):D730\u20135. https:\/\/doi.org\/10.1093\/nar\/gkq1229.","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"2538_CR26","doi-asserted-by":"publisher","first-page":"D374","DOI":"10.1093\/nar\/gkt887","volume":"42","author":"R Mosca","year":"2014","unstructured":"Mosca R, C\u00e9ol A, Stein A, Olivella R, Aloy P. 3did: a catalog of domain-based interactions of known three-dimensional structure. Nucleic Acids Res. 2014;42(Database issue):D374\u20139. https:\/\/doi.org\/10.1093\/nar\/gkt887.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"2538_CR27","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"HM Berman","year":"2000","unstructured":"Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The Protein Data Bank. Nucleic Acids Res. 2000;28(1):235\u201342. https:\/\/doi.org\/10.1093\/nar\/28.1.235.","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"2538_CR28","doi-asserted-by":"publisher","first-page":"D793","DOI":"10.1093\/nar\/gks1055","volume":"41","author":"A Kamburov","year":"2013","unstructured":"Kamburov A, Stelzl U, Lehrach H, Herwig R. The ConsensusPathDB interaction database: 2013 update. Nucleic Acids Res. 2013;41(Database issue):D793\u2013800.","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"2538_CR29","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1016\/j.molcel.2012.05.037","volume":"46","author":"JD Ellis","year":"2012","unstructured":"Ellis JD, Barrios-Rodiles M, \u00c7olak R, Irimia M, Kim T, Calarco JA, et al. Tissue-Specific Alternative Splicing Remodels Protein-Protein Interaction Networks. Mol Cell. 2012;46(6):884\u201392.","journal-title":"Mol Cell"},{"issue":"10","key":"2538_CR30","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1101\/gr.220962.117","volume":"27","author":"J Tapial","year":"2017","unstructured":"Tapial J, Ha KCH, Sterne-Weiler T, Gohr A, Braunschweig U, Hermoso-Pulido A, et al. An atlas of alternative splicing profiles and functional associations reveals new regulatory programs and genes that simultaneously express multiple major isoforms. Genome Res. 2017;27(10):1759\u201368.","journal-title":"Genome Res"},{"issue":"1","key":"2538_CR31","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/ncomms1303","volume":"2","author":"PJ Seo","year":"2011","unstructured":"Seo PJ, Kim MJ, Ryu J-Y, Jeong E-Y, Park C-M. Two splice variants of the IDD14 transcription factor competitively form nonfunctional heterodimers which may regulate starch metabolism. Nat Commun. 2011;2(1):303. https:\/\/doi.org\/10.1038\/ncomms1303.","journal-title":"Nat Commun"},{"issue":"1","key":"2538_CR32","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1186\/1471-2105-13-226","volume":"13","author":"A Alexeyenko","year":"2012","unstructured":"Alexeyenko A, Lee W, Pernemalm M, Guegan J, Dessen P, Lazar V, et al. Network enrichment analysis: extension of gene-set enrichment analysis to gene networks. BMC Bioinformatics. 2012;13(1):226. https:\/\/doi.org\/10.1186\/1471-2105-13-226.","journal-title":"BMC Bioinformatics"},{"issue":"13","key":"2538_CR33","doi-asserted-by":"publisher","first-page":"9912","DOI":"10.1016\/S0021-9258(17)36969-7","volume":"269","author":"MG Tansey","year":"1994","unstructured":"Tansey MG, Luby-Phelps K, Kamm KE, Stull JT. Ca(2+)-dependent phosphorylation of myosin light chain kinase decreases the Ca2+ sensitivity of light chain phosphorylation within smooth muscle cells. J Biol Chem. 1994;269(13):9912\u201320.","journal-title":"J Biol Chem"},{"issue":"26","key":"2538_CR34","doi-asserted-by":"publisher","first-page":"8940","DOI":"10.1523\/JNEUROSCI.0026-12.2012","volume":"32","author":"CN Hall","year":"2012","unstructured":"Hall CN, Klein-Fl\u00fcgge MC, Howarth C, Attwell D. Oxidative phosphorylation, not glycolysis, powers presynaptic and postsynaptic mechanisms underlying brain information processing. J Neurosci. 2012;32(26):8940\u201351. https:\/\/doi.org\/10.1523\/JNEUROSCI.0026-12.2012.","journal-title":"J Neurosci"},{"issue":"6","key":"2538_CR35","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1523\/JNEUROSCI.5549-08.2009","volume":"29","author":"BG Sanganahalli","year":"2009","unstructured":"Sanganahalli BG, Herman P, Blumenfeld H, Hyder F. Oxidative neuroenergetics in event-related paradigms. J Neurosci. 2009;29(6):1707\u201318. https:\/\/doi.org\/10.1523\/JNEUROSCI.5549-08.2009.","journal-title":"J Neurosci"},{"key":"2538_CR36","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3389\/fncom.2019.00049","volume":"13","author":"RC Vergara","year":"2019","unstructured":"Vergara RC, Jaramillo-Riveri S, Luarte A, Mo\u00ebnne-Loccoz C, Fuentes R, Couve A, et al. The Energy Homeostasis Principle: Neuronal Energy Regulation Drives Local Network Dynamics Generating Behavior. Front Comput Neurosci. 2019;13:49. https:\/\/doi.org\/10.3389\/fncom.2019.00049.","journal-title":"Front Comput Neurosci"},{"issue":"17","key":"2538_CR37","doi-asserted-by":"publisher","first-page":"6409","DOI":"10.1073\/pnas.0710766105","volume":"105","author":"F Du","year":"2008","unstructured":"Du F, Zhu X-H, Zhang Y, Friedman M, Zhang N, Ugurbil K, et al. Tightly coupled brain activity and cerebral ATP metabolic rate. Proc Natl Acad Sci U S A. 2008;105(17):6409\u201314. https:\/\/doi.org\/10.1073\/pnas.0710766105.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"2538_CR38","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1038\/jcbfm.2012.35","volume":"32","author":"C Howarth","year":"2012","unstructured":"Howarth C, Gleeson P, Attwell D. Updated energy budgets for neural computation in the neocortex and cerebellum. J Cereb Blood Flow Metab. 2012;32(7):1222\u201332. https:\/\/doi.org\/10.1038\/jcbfm.2012.35.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"4","key":"2538_CR39","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.neuron.2015.03.035","volume":"86","author":"PJ Magistretti","year":"2015","unstructured":"Magistretti PJ, Allaman I. A cellular perspective on brain energy metabolism and functional imaging. Neuron. 2015;86(4):883\u2013901. https:\/\/doi.org\/10.1016\/j.neuron.2015.03.035.","journal-title":"Neuron"},{"key":"2538_CR40","doi-asserted-by":"publisher","first-page":"5","DOI":"10.7554\/eLife.13374","volume":"10","author":"X Zheng","year":"2016","unstructured":"Zheng X, Boyer L, Jin M, Mertens J, Kim Y, Ma L, et al. Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation. Elife. 2016;10:5. Available from:. https:\/\/doi.org\/10.7554\/eLife.13374.","journal-title":"Elife"},{"issue":"4","key":"2538_CR41","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.cell.2005.03.012","volume":"121","author":"PR Hiesinger","year":"2005","unstructured":"Hiesinger PR, Fayyazuddin A, Mehta SQ, Rosenmund T, Schulze KL, Zhai RG, et al. The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila. Cell. 2005;121(4):607\u201320. https:\/\/doi.org\/10.1016\/j.cell.2005.03.012.","journal-title":"Cell"},{"issue":"1","key":"2538_CR42","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.1038\/s41467-021-22389-5","volume":"12","author":"K Aoto","year":"2021","unstructured":"Aoto K, Kato M, Akita T, Nakashima M, Mutoh H, Akasaka N, et al. ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H+-ATPases is essential for brain development in humans and mice. Nat Commun. 2021;12(1):2107. https:\/\/doi.org\/10.1038\/s41467-021-22389-5.","journal-title":"Nat Commun"},{"issue":"25","key":"2538_CR43","doi-asserted-by":"publisher","first-page":"17164","DOI":"10.1074\/jbc.M600927200","volume":"281","author":"S Po\u00eba-Guyon","year":"2006","unstructured":"Po\u00eba-Guyon S, Amar M, Fossier P, Morel N. Alternative splicing controls neuronal expression of v-ATPase subunit a1 and sorting to nerve terminals. J Biol Chem. 2006;281(25):17164\u201372. https:\/\/doi.org\/10.1074\/jbc.M600927200.","journal-title":"J Biol Chem"},{"issue":"38","key":"2538_CR44","doi-asserted-by":"publisher","first-page":"23527","DOI":"10.1073\/pnas.2003662117","volume":"117","author":"L Redlingsh\u00f6fer","year":"2020","unstructured":"Redlingsh\u00f6fer L, McLeod F, Chen Y, Camus MD, Burden JJ, Palomer E, et al. Clathrin light chain diversity regulates membrane deformation in vitro and synaptic vesicle formation in vivo. Proc Natl Acad Sci U S A. 2020;117(38):23527\u201338.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"2538_CR45","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/ng.2653","volume":"45","author":"J Lonsdale","year":"2013","unstructured":"Lonsdale J, Thomas J, Salvatore M, Phillips R, Lo E, Shad S, et al. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013;45(6):580\u20135. https:\/\/doi.org\/10.1038\/ng.2653.","journal-title":"Nat Genet"},{"issue":"10","key":"2538_CR46","doi-asserted-by":"publisher","first-page":"e1008287","DOI":"10.1371\/journal.pcbi.1008287","volume":"16","author":"JM Rodriguez","year":"2020","unstructured":"Rodriguez JM, Pozo F, di Domenico T, Vazquez J, Tress ML. An analysis of tissue-specific alternative splicing at the protein level. Orengo CA, editor. PLoS Comput Biol. 2020;16(10):e1008287.","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"2538_CR47","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.neuron.2015.05.004","volume":"87","author":"B Raj","year":"2015","unstructured":"Raj B, Blencowe BJ. Alternative Splicing in the Mammalian Nervous System: Recent Insights into Mechanisms and Functional Roles. Neuron. 2015;87(1):14\u201327. https:\/\/doi.org\/10.1016\/j.neuron.2015.05.004.","journal-title":"Neuron"},{"key":"2538_CR48","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3389\/fmolb.2018.00012","volume":"5","author":"C-H Su","year":"2018","unstructured":"Su C-H, Dhananjaya D, Tarn W-Y. Alternative Splicing in Neurogenesis and Brain Development. Front Mol Biosci. 2018;5:12.","journal-title":"Front Mol Biosci"},{"issue":"11","key":"2538_CR49","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1055\/s-0039-1695009","volume":"119","author":"D Bongiovanni","year":"2019","unstructured":"Bongiovanni D, Santamaria G, Klug M, Santovito D, Felicetta A, Hristov M, et al. Transcriptome Analysis of Reticulated Platelets Reveals a Prothrombotic Profile. Thromb Haemost. 2019;119(11):1795\u2013806. https:\/\/doi.org\/10.1055\/s-0039-1695009.","journal-title":"Thromb Haemost"},{"issue":"9","key":"2538_CR50","first-page":"996","volume":"23","author":"KA Ault","year":"1995","unstructured":"Ault KA, Knowles C. In vivo biotinylation demonstrates that reticulated platelets are the youngest platelets in circulation. Exp Hematol. 1995;23(9):996\u20131001.","journal-title":"Exp Hematol"},{"issue":"6","key":"2538_CR51","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1172\/JCI106064","volume":"48","author":"S Karpatkin","year":"1969","unstructured":"Karpatkin S. Heterogeneity of human platelets. II. Functional evidence suggestive of young and old platelets. J Clin Invest. 1969;48(6):1083\u20137.","journal-title":"J Clin Invest"},{"issue":"05","key":"2538_CR52","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1160\/TH12-09-0709","volume":"109","author":"F Cesari","year":"2013","unstructured":"Cesari F, Marcucci R, Gori AM, Caporale R, Fanelli A, Casola G, et al. Reticulated platelets predict cardiovascular death in acute coronary syndrome patients. Thromb Haemost. 2013;109(05):846\u201353. https:\/\/doi.org\/10.1160\/TH12-09-0709.","journal-title":"Thromb Haemost"},{"issue":"9","key":"2538_CR53","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/j.jacc.2008.05.031","volume":"52","author":"S Guthikonda","year":"2008","unstructured":"Guthikonda S, Alviar CL, Vaduganathan M, Arikan M, Tellez A, DeLao T, et al. Role of reticulated platelets and platelet size heterogeneity on platelet activity after dual antiplatelet therapy with aspirin and clopidogrel in patients with stable coronary artery disease. J Am Coll Cardiol. 2008;52(9):743\u20139. https:\/\/doi.org\/10.1016\/j.jacc.2008.05.031.","journal-title":"J Am Coll Cardiol"},{"key":"2538_CR54","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.thromres.2016.06.002","volume":"144","author":"T Muronoi","year":"2016","unstructured":"Muronoi T, Koyama K, Nunomiya S, Lefor AK, Wada M, Koinuma T, et al. Immature platelet fraction predicts coagulopathy-related platelet consumption and mortality in patients with sepsis. Thromb Res. 2016;144:169\u201375. https:\/\/doi.org\/10.1016\/j.thromres.2016.06.002.","journal-title":"Thromb Res"},{"issue":"1","key":"2538_CR55","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/s41598-017-18985-5","volume":"8","author":"G Nassa","year":"2018","unstructured":"Nassa G, Giurato G, Cimmino G, Rizzo F, Ravo M, Salvati A, et al. Splicing of platelet resident pre-mRNAs upon activation by physiological stimuli results in functionally relevant proteome modifications. Sci Rep. 2018;8(1):498. https:\/\/doi.org\/10.1038\/s41598-017-18985-5.","journal-title":"Sci Rep"},{"key":"2538_CR56","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.11752","volume":"5","author":"J Vaquero-Garcia","year":"2016","unstructured":"Vaquero-Garcia J, Barrera A, Gazzara MR, Gonz\u00e1lez-Vallinas J, Lahens NF, Hogenesch JB, et al. A new view of transcriptome complexity and regulation through the lens of local splicing variations. Elife. 2016;5:e11752.","journal-title":"Elife"},{"issue":"D1","key":"2538_CR57","doi-asserted-by":"publisher","first-page":"D649","DOI":"10.1093\/nar\/gkx1132","volume":"46","author":"A Fabregat","year":"2018","unstructured":"Fabregat A, Jupe S, Matthews L, Sidiropoulos K, Gillespie M, Garapati P, et al. The Reactome Pathway Knowledgebase. Nucleic Acids Res. 2018;46(D1):D649\u201355. https:\/\/doi.org\/10.1093\/nar\/gkx1132.","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"2538_CR58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024549","volume":"6","author":"FAJL Scheer","year":"2011","unstructured":"Scheer FAJL, Michelson AD, Frelinger AL 3rd, Evoniuk H, Kelly EE, McCarthy M, et al. The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors. PLoS One. 2011;6(9):e24549.","journal-title":"PLoS One"},{"issue":"12","key":"2538_CR59","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1161\/01.RES.0000251742.71301.16","volume":"99","author":"S Offermanns","year":"2006","unstructured":"Offermanns S. Activation of Platelet Function Through G Protein\u2013Coupled Receptors. Circ Res. 2006;99(12):1293\u2013304. https:\/\/doi.org\/10.1161\/01.RES.0000251742.71301.16.","journal-title":"Circ Res"},{"issue":"7835","key":"2538_CR60","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/s41586-020-2888-2","volume":"587","author":"M Marti-Solano","year":"2020","unstructured":"Marti-Solano M, Crilly SE, Malinverni D, Munk C, Harris M, Pearce A, et al. Combinatorial expression of GPCR isoforms affects signalling and drug responses. Nature. 2020;587(7835):650\u20136. https:\/\/doi.org\/10.1038\/s41586-020-2888-2.","journal-title":"Nature"},{"issue":"12","key":"2538_CR61","doi-asserted-by":"publisher","first-page":"2678","DOI":"10.1111\/j.1538-7836.2006.02229.x","volume":"4","author":"G Jalagadugula","year":"2006","unstructured":"Jalagadugula G, Dhanasekaran DN, Kim S, Kunapuli SP, Rao AK. Early growth response transcription factor EGR-1 regulates Galphaq gene in megakaryocytic cells. J Thromb Haemost. 2006;4(12):2678\u201386.","journal-title":"J Thromb Haemost"},{"issue":"6","key":"2538_CR62","doi-asserted-by":"publisher","first-page":"3918","DOI":"10.1074\/jbc.M112.429936","volume":"288","author":"SF Moore","year":"2013","unstructured":"Moore SF, van den Bosch MTJ, Hunter RW, Sakamoto K, Poole AW, Hers I. Dual regulation of glycogen synthase kinase 3 (GSK3)\u03b1\/\u03b2 by protein kinase C (PKC)\u03b1 and Akt promotes thrombin-mediated integrin \u03b1IIb\u03b23 activation and granule secretion in platelets. J Biol Chem. 2013;288(6):3918\u201328. https:\/\/doi.org\/10.1074\/jbc.M112.429936.","journal-title":"J Biol Chem"},{"issue":"3","key":"2538_CR63","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1111\/j.1538-7836.2009.03722.x","volume":"8","author":"MT Harper","year":"2010","unstructured":"Harper MT, Poole AW. Diverse functions of protein kinase C isoforms in platelet activation and thrombus formation. J Thromb Haemost. 2010;8(3):454\u201362. https:\/\/doi.org\/10.1111\/j.1538-7836.2009.03722.x.","journal-title":"J Thromb Haemost"},{"issue":"1","key":"2538_CR64","doi-asserted-by":"publisher","first-page":"62","DOI":"10.3109\/09537104.2012.761686","volume":"25","author":"CM Williams","year":"2014","unstructured":"Williams CM, Harper MT, Poole AW. PKC\u03b1 negatively regulates in vitro proplatelet formation and in vivo platelet production in mice. Platelets. 2014;25(1):62\u20138.","journal-title":"Platelets"},{"issue":"6","key":"2538_CR65","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1093\/ajcp\/98.6.637","volume":"98","author":"KA Ault","year":"1992","unstructured":"Ault KA, Rinder HM, Mitchell J, Carmody MB, Vary CP, Hillman RS. The significance of platelets with increased RNA content (reticulated platelets). A measure of the rate of thrombopoiesis. Am J Clin Pathol. 1992;98(6):637\u201346. https:\/\/doi.org\/10.1093\/ajcp\/98.6.637.","journal-title":"Am J Clin Pathol"},{"issue":"5","key":"2538_CR66","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1002\/ana.410360515","volume":"36","author":"L B\u00f6","year":"1994","unstructured":"B\u00f6 L, Dawson TM, Wesselingh S, M\u00f6rk S, Choi S, Kong PA, et al. Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann Neurol. 1994;36(5):778\u201386. https:\/\/doi.org\/10.1002\/ana.410360515.","journal-title":"Ann Neurol"},{"issue":"4","key":"2538_CR67","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1097\/01.jnen.0000225024.12074.80","volume":"65","author":"SK Ludwin","year":"2006","unstructured":"Ludwin SK. The pathogenesis of multiple sclerosis: relating human pathology to experimental studies. J Neuropathol Exp Neurol. 2006;65(4):305\u201318. https:\/\/doi.org\/10.1097\/01.jnen.0000225024.12074.80.","journal-title":"J Neuropathol Exp Neurol"},{"issue":"7","key":"2538_CR68","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.autrev.2019.05.010","volume":"18","author":"M Hecker","year":"2019","unstructured":"Hecker M, R\u00fcge A, Putscher E, Boxberger N, Rommer PS, Fitzner B, et al. Aberrant expression of alternative splicing variants in multiple sclerosis - A systematic review. Autoimmun Rev. 2019;18(7):721\u201332. https:\/\/doi.org\/10.1016\/j.autrev.2019.05.010.","journal-title":"Autoimmun Rev"},{"issue":"1","key":"2538_CR69","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1186\/s40478-019-0855-7","volume":"7","author":"ML Elkjaer","year":"2019","unstructured":"Elkjaer ML, Frisch T, Reynolds R, Kacprowski T, Burton M, Kruse TA, et al. Molecular signature of different lesion types in the brain white matter of patients with progressive multiple sclerosis. Acta Neuropathol Commun. 2019;7(1):205. https:\/\/doi.org\/10.1186\/s40478-019-0855-7.","journal-title":"Acta Neuropathol Commun"},{"issue":"2-3","key":"2538_CR70","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s004210000276","volume":"83","author":"H Gissel","year":"2000","unstructured":"Gissel H. Ca2+ accumulation and cell damage in skeletal muscle during low frequency stimulation. Eur J Appl Physiol. 2000;83(2-3):175\u201380. https:\/\/doi.org\/10.1007\/s004210000276.","journal-title":"Eur J Appl Physiol"},{"issue":"1700","key":"2538_CR71","doi-asserted-by":"publisher","first-page":"371(1700)","DOI":"10.1098\/rstb.2015.0425","volume":"5","author":"J Mal\u00e9th","year":"2016","unstructured":"Mal\u00e9th J, Hegyi P. Ca2+ toxicity and mitochondrial damage in acute pancreatitis: translational overview. Philos Trans R Soc Lond B Biol Sci. 2016;5(1700):371(1700). Available from:. https:\/\/doi.org\/10.1098\/rstb.2015.0425.","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"6","key":"2538_CR72","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1191\/1352458503ms965oa","volume":"9","author":"A Minagar","year":"2003","unstructured":"Minagar A, Alexander JS. Blood-brain barrier disruption in multiple sclerosis. Mult Scler. 2003;9(6):540\u20139. https:\/\/doi.org\/10.1191\/1352458503ms965oa.","journal-title":"Mult Scler"},{"issue":"3","key":"2538_CR73","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1007\/BF00296505","volume":"90","author":"L Claudio","year":"1995","unstructured":"Claudio L, Raine CS, Brosnan CF. Evidence of persistent blood-brain barrier abnormalities in chronic-progressive multiple sclerosis. Acta Neuropathol. 1995;90(3):228\u201338.","journal-title":"Acta Neuropathol"},{"issue":"8","key":"2538_CR74","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/j.arcmed.2014.11.013","volume":"45","author":"GG Ortiz","year":"2014","unstructured":"Ortiz GG, Pacheco-Mois\u00e9s FP, Mac\u00edas-Islas M\u00c1, Flores-Alvarado LJ, Mireles-Ram\u00edrez MA, Gonz\u00e1lez-Renovato ED, et al. Role of the blood-brain barrier in multiple sclerosis. Arch Med Res. 2014;45(8):687\u201397.","journal-title":"Arch Med Res"},{"issue":"4","key":"2538_CR75","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1002\/ana.21117","volume":"61","author":"A Ascherio","year":"2007","unstructured":"Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann Neurol. 2007;61(4):288\u201399.","journal-title":"Ann Neurol"},{"issue":"9","key":"2538_CR76","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1093\/brain\/awq192","volume":"133","author":"SE Baranzini","year":"2010","unstructured":"Baranzini SE, Srinivasan R, Khankhanian P, Okuda DT, Nelson SJ, Matthews PM, et al. Genetic variation influences glutamate concentrations in brains of patients with multiple sclerosis. Brain. 2010;133(9):2603\u201311. https:\/\/doi.org\/10.1093\/brain\/awq192.","journal-title":"Brain"},{"issue":"3","key":"2538_CR77","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1177\/1352458512454345","volume":"19","author":"EMM Strijbis","year":"2013","unstructured":"Strijbis EMM, Inkster B, Vounou M, Naegelin Y, Kappos L, Radue E-W, et al. Glutamate gene polymorphisms predict brain volumes in multiple sclerosis. Mult Scler. 2013;19(3):281\u20138. https:\/\/doi.org\/10.1177\/1352458512454345.","journal-title":"Mult Scler"},{"issue":"1","key":"2538_CR78","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/gm217","volume":"3","author":"JH Wang","year":"2011","unstructured":"Wang JH, Pappas D, De Jager PL, Pelletier D, de Bakker PI, Kappos L, et al. Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data. Genome Med. 2011;3(1):3. https:\/\/doi.org\/10.1186\/gm217.","journal-title":"Genome Med"},{"key":"2538_CR79","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-60761-795-2_1","volume":"661","author":"Y Keshet","year":"2010","unstructured":"Keshet Y, Seger R. The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions. Methods Mol Biol. 2010;661:3\u201338. https:\/\/doi.org\/10.1007\/978-1-60761-795-2_1.","journal-title":"Methods Mol Biol"},{"issue":"6824","key":"2538_CR80","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/35065000","volume":"410","author":"L Chang","year":"2001","unstructured":"Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature. 2001;410(6824):37\u201340. https:\/\/doi.org\/10.1038\/35065000.","journal-title":"Nature"},{"issue":"1","key":"2538_CR81","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.clim.2015.02.011","volume":"158","author":"K Shchetynsky","year":"2015","unstructured":"Shchetynsky K, Protsyuk D, Ronninger M, Diaz-Gallo L-M, Klareskog L, Padyukov L. Gene-gene interaction and RNA splicing profiles of MAP2K4 gene in rheumatoid arthritis. Clin Immunol. 2015;158(1):19\u201328.","journal-title":"Clin Immunol"},{"issue":"2","key":"2538_CR82","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/gene.2012.55","volume":"14","author":"T Tuller","year":"2013","unstructured":"Tuller T, Atar S, Ruppin E, Gurevich M, Achiron A. Common and specific signatures of gene expression and protein-protein interactions in autoimmune diseases. Genes Immun. 2013;14(2):67\u201382.","journal-title":"Genes Immun"},{"key":"2538_CR83","doi-asserted-by":"publisher","unstructured":"GJA t B, Bolk J, `t Hart BA, Laman JD. Multiple sclerosis is linked to MAPKERK overactivity in microglia. J Mol Med. 2021; Available from:. https:\/\/doi.org\/10.1007\/s00109-021-02080-4.","DOI":"10.1007\/s00109-021-02080-4"},{"issue":"7672","key":"2538_CR84","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/nature23672","volume":"549","author":"E Mass","year":"2017","unstructured":"Mass E, Jacome-Galarza CE, Blank T, Lazarov T, Durham BH, Ozkaya N, et al. A somatic mutation in erythro-myeloid progenitors causes neurodegenerative disease. Nature. 2017;549(7672):389\u201393. https:\/\/doi.org\/10.1038\/nature23672.","journal-title":"Nature"},{"issue":"19","key":"2538_CR85","doi-asserted-by":"publisher","first-page":"9671","DOI":"10.1073\/pnas.1818347116","volume":"116","author":"E Kotelnikova","year":"2019","unstructured":"Kotelnikova E, Kiani NA, Messinis D, Pertsovskaya I, Pliaka V, Bernardo-Faura M, et al. MAPK pathway and B cells overactivation in multiple sclerosis revealed by phosphoproteomics and genomic analysis. Proc Natl Acad Sci U S A. 2019;116(19):9671\u20136. https:\/\/doi.org\/10.1073\/pnas.1818347116.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"19","key":"2538_CR86","doi-asserted-by":"publisher","first-page":"3728","DOI":"10.1128\/MCB.00688-13","volume":"33","author":"DN Krementsov","year":"2013","unstructured":"Krementsov DN, Thornton TM, Teuscher C, Rincon M. The emerging role of p38 mitogen-activated protein kinase in multiple sclerosis and its models. Mol Cell Biol. 2013;33(19):3728\u201334.","journal-title":"Mol Cell Biol"},{"key":"2538_CR87","doi-asserted-by":"crossref","unstructured":"Bernardo-Faura M, Rinas M, Wirbel J, Pertsovskaya I, Pliaka V, Messinis DE, Vila G, Sakellaropoulos T, Faigle W, Stridh P, Behrens JR. Prediction of combination therapies based on topological modeling of the immune signaling network in Multiple Sclerosis. Genome Medicine. 2021;13(1):1-6.","DOI":"10.1186\/s13073-021-00925-8"},{"issue":"8","key":"2538_CR88","doi-asserted-by":"publisher","first-page":"3419","DOI":"10.1172\/JCI74523","volume":"124","author":"H Maatz","year":"2014","unstructured":"Maatz H, Jens M, Liss M, Schafer S, Heinig M, Kirchner M, et al. RNA-binding protein RBM20 represses splicing to orchestrate cardiac pre-mRNA processing. J Clin Invest. 2014;124(8):3419\u201330. https:\/\/doi.org\/10.1172\/JCI74523.","journal-title":"J Clin Invest"},{"issue":"1","key":"2538_CR89","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.gene.2015.06.027","volume":"569","author":"F Sheikh","year":"2015","unstructured":"Sheikh F, Lyon RC, Chen J. Functions of myosin light chain-2 (MYL2) in cardiac muscle and disease. Gene. 2015;569(1):14\u201320.","journal-title":"Gene"},{"issue":"Suppl 1","key":"2538_CR90","first-page":"S20","volume":"85","author":"AM Matyushenko","year":"2020","unstructured":"Matyushenko AM, Levitsky DI. Molecular Mechanisms of Pathologies of Skeletal and Cardiac Muscles Caused by Point Mutations in the Tropomyosin Genes. Biochemistry. 2020;85(Suppl 1):S20\u201333.","journal-title":"Biochemistry"},{"issue":"9","key":"2538_CR91","doi-asserted-by":"publisher","first-page":"2229","DOI":"10.1002\/ajmg.a.34097","volume":"155A","author":"C Caleshu","year":"2011","unstructured":"Caleshu C, Sakhuja R, Nussbaum RL, Schiller NB, Ursell PC, Eng C, et al. Furthering the link between the sarcomere and primary cardiomyopathies: restrictive cardiomyopathy associated with multiple mutations in genes previously associated with hypertrophic or dilated cardiomyopathy. Am J Med Genet A. 2011;155A(9):2229\u201335. https:\/\/doi.org\/10.1002\/ajmg.a.34097.","journal-title":"Am J Med Genet A"},{"issue":"12","key":"2538_CR92","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051621","volume":"7","author":"MJ Brody","year":"2012","unstructured":"Brody MJ, Hacker TA, Patel JR, Feng L, Sadoshima J, Tevosian SG, et al. Ablation of the cardiac-specific gene leucine-rich repeat containing 10 (Lrrc10) results in dilated cardiomyopathy. PLoS One. 2012;7(12):e51621.","journal-title":"PLoS One"},{"issue":"11","key":"2538_CR93","doi-asserted-by":"publisher","first-page":"7003","DOI":"10.1074\/jbc.M114.596676","volume":"290","author":"TM Gupte","year":"2015","unstructured":"Gupte TM, Haque F, Gangadharan B, Sunitha MS, Mukherjee S, Anandhan S, et al. Mechanistic Heterogeneity in Contractile Properties of \u03b1-Tropomyosin (TPM1) Mutants Associated with Inherited Cardiomyopathies*. J Biol Chem. 2015;290(11):7003\u201315.","journal-title":"J Biol Chem"},{"issue":"12","key":"2538_CR94","doi-asserted-by":"publisher","first-page":"2379","DOI":"10.1111\/febs.13286","volume":"282","author":"W Huang","year":"2015","unstructured":"Huang W, Liang J, Yuan C-C, Kazmierczak K, Zhou Z, Morales A, et al. Novel familial dilated cardiomyopathy mutation in MYL2 affects the structure and function of myosin regulatory light chain. FEBS J. 2015;282(12):2379\u201393.","journal-title":"FEBS J"},{"issue":"7","key":"2538_CR95","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1056\/NEJMoa1110186","volume":"366","author":"DS Herman","year":"2012","unstructured":"Herman DS, Lam L, Taylor MRG, Wang L, Teekakirikul P, Christodoulou D, et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012;366(7):619\u201328. https:\/\/doi.org\/10.1056\/NEJMoa1110186.","journal-title":"N Engl J Med"},{"issue":"9","key":"2538_CR96","doi-asserted-by":"publisher","first-page":"e0138568","DOI":"10.1371\/journal.pone.0138568","volume":"10","author":"S Marston","year":"2015","unstructured":"Marston S, Montgiraud C, Munster AB, Copeland O, Choi O, Dos Remedios C, et al. OBSCN Mutations Associated with Dilated Cardiomyopathy and Haploinsufficiency. PLoS One. 2015;10(9):e0138568.","journal-title":"PLoS One"},{"issue":"3","key":"2538_CR97","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/s12551-017-0264-8","volume":"9","author":"S Marston","year":"2017","unstructured":"Marston S. Obscurin variants and inherited cardiomyopathies. Biophys Rev. 2017;9(3):239\u201343. https:\/\/doi.org\/10.1007\/s12551-017-0264-8.","journal-title":"Biophys Rev"},{"issue":"7","key":"2538_CR98","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1161\/CIRCRESAHA.116.309396","volume":"121","author":"EM McNally","year":"2017","unstructured":"McNally EM, Mestroni L. Dilated Cardiomyopathy: Genetic Determinants and Mechanisms. Circ Res. 2017;121(7):731\u201348. https:\/\/doi.org\/10.1161\/CIRCRESAHA.116.309396.","journal-title":"Circ Res"},{"issue":"5","key":"2538_CR99","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1161\/CIRCEP.115.002745","volume":"8","author":"NJ Boczek","year":"2015","unstructured":"Boczek NJ, Ye D, Jin F, Tester DJ, Huseby A, Bos JM, et al. Identification and Functional Characterization of a Novel CACNA1C-Mediated Cardiac Disorder Characterized by Prolonged QT Intervals With Hypertrophic Cardiomyopathy, Congenital Heart Defects, and Sudden Cardiac Death. Circ Arrhythm Electrophysiol. 2015;8(5):1122\u201332.","journal-title":"Circ Arrhythm Electrophysiol"},{"issue":"3","key":"2538_CR100","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/S0014-5793(01)02866-6","volume":"505","author":"J Mouton","year":"2001","unstructured":"Mouton J, Ronjat M, Jona I, Villaz M, Feltz A, Maulet Y. Skeletal and cardiac ryanodine receptors bind to the Ca(2+)-sensor region of dihydropyridine receptor alpha(1C) subunit. FEBS Lett. 2001;505(3):441\u20134. https:\/\/doi.org\/10.1016\/S0014-5793(01)02866-6.","journal-title":"FEBS Lett"},{"issue":"1","key":"2538_CR101","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28(1):27\u201330.","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"2538_CR102","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1016\/j.bbadis.2013.06.008","volume":"1832","author":"S Ather","year":"2013","unstructured":"Ather S, Respress JL, Li N, Wehrens XHT. Alterations in ryanodine receptors and related proteins in heart failure. Biochim Biophys Acta. 2013;1832(12):2425\u201331. https:\/\/doi.org\/10.1016\/j.bbadis.2013.06.008.","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"2538_CR103","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jjcc.2008.10.008","volume":"53","author":"M Yano","year":"2009","unstructured":"Yano M, Yamamoto T, Kobayashi S, Matsuzaki M. Role of ryanodine receptor as a Ca2+ regulatory center in normal and failing hearts. J Cardiol. 2009;53(1):1\u20137. https:\/\/doi.org\/10.1016\/j.jjcc.2008.10.008.","journal-title":"J Cardiol"},{"issue":"16","key":"2538_CR104","doi-asserted-by":"publisher","first-page":"20(16)","DOI":"10.3390\/ijms20163986","volume":"16","author":"F Moccia","year":"2019","unstructured":"Moccia F, Lodola F, Stadiotti I, Pilato CA, Bellin M, Carugo S, et al. Calcium as a Key Player in Arrhythmogenic Cardiomyopathy: Adhesion Disorder or Intracellular Alteration? Int J Mol Sci. 2019;16(16):20(16). Available from:. https:\/\/doi.org\/10.3390\/ijms20163986.","journal-title":"Int J Mol Sci"},{"issue":"12","key":"2538_CR105","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/s41583-018-0079-z","volume":"19","author":"SR Jaffrey","year":"2018","unstructured":"Jaffrey SR, Wilkinson MF. Nonsense-mediated RNA decay in the brain: emerging modulator of neural development and disease. Nat Rev Neurosci. 2018;19(12):715\u201328.","journal-title":"Nat Rev Neurosci"},{"issue":"1","key":"2538_CR106","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.molcel.2005.05.026","volume":"19","author":"C Schwerk","year":"2005","unstructured":"Schwerk C, Schulze-Osthoff K. Regulation of apoptosis by alternative pre-mRNA splicing. Mol Cell. 2005;19(1):1\u201313.","journal-title":"Mol Cell"},{"issue":"W1","key":"2538_CR107","doi-asserted-by":"publisher","first-page":"W98","DOI":"10.1093\/nar\/gkw373","volume":"44","author":"M List","year":"2016","unstructured":"List M, Alcaraz N, Dissing-Hansen M, Ditzel HJ, Mollenhauer J, Baumbach J. KeyPathwayMinerWeb: online multi-omics network enrichment. Nucleic Acids Res. 2016;44(W1):W98\u2013104.","journal-title":"Nucleic Acids Res"},{"key":"2538_CR108","doi-asserted-by":"publisher","first-page":"bar030","DOI":"10.1093\/database\/bar030","volume":"2011","author":"RJ Kinsella","year":"2011","unstructured":"Kinsella RJ, K\u00e4h\u00e4ri A, Haider S, Zamora J, Proctor G, Spudich G, et al. Ensembl BioMarts: a hub for data retrieval across taxonomic space. Database. 2011;2011:bar030.","journal-title":"Database"},{"issue":"W1","key":"2538_CR109","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","volume":"44","author":"MV Kuleshov","year":"2016","unstructured":"Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44(W1):W90\u20137. https:\/\/doi.org\/10.1093\/nar\/gkw377.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"2538_CR110","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1186\/s12859-016-1203-6","volume":"17","author":"M Signorelli","year":"2016","unstructured":"Signorelli M, Vinciotti V, Wit EC. NEAT: an efficient network enrichment analysis test. BMC Bioinformatics. 2016;17(1):352. https:\/\/doi.org\/10.1186\/s12859-016-1203-6.","journal-title":"BMC Bioinformatics"},{"key":"2538_CR111","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J Royal Stat Soc: Ser B (Methodological). 1995;57:289\u2013300. Available from:. https:\/\/doi.org\/10.1111\/j.2517-6161.1995.tb02031.x.","journal-title":"J Royal Stat Soc: Ser B (Methodological)"},{"issue":"7","key":"2538_CR112","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1016\/j.cell.2014.11.035","volume":"159","author":"M Irimia","year":"2014","unstructured":"Irimia M, Weatheritt RJ, Ellis JD, Parikshak NN, Gonatopoulos-Pournatzis T, Babor M, et al. A highly conserved program of neuronal microexons is misregulated in autistic brains. Cell. 2014;159(7):1511\u201323. https:\/\/doi.org\/10.1016\/j.cell.2014.11.035.","journal-title":"Cell"},{"issue":"1","key":"2538_CR113","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15\u201321.","journal-title":"Bioinformatics"},{"key":"2538_CR114","unstructured":"Van Der Walt S, Chris Colbert S, Varoquaux G. The NumPy array: a structure for efficient numerical computation. arXiv [cs.MS]. 2011; Available from: http:\/\/arxiv.org\/abs\/1102.1523."},{"key":"2538_CR115","doi-asserted-by":"publisher","unstructured":"McKinney W, Others. Data structures for statistical computing in python. Proceedings of the 9th Python in Science Conference. 2010;445:51\u20136. https:\/\/doi.org\/10.25080\/Majora-92bf1922-00a.","DOI":"10.25080\/Majora-92bf1922-00a"},{"key":"2538_CR116","doi-asserted-by":"crossref","unstructured":"Hagberg A, Swart P, S Chult D. Exploring network structure, dynamics, and function using networkx. Proceedings of the 7th Python in Science Conference (SciPy2008). 2008;11-15.","DOI":"10.25080\/TCWV9851"},{"issue":"3","key":"2538_CR117","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","volume":"17","author":"P Virtanen","year":"2020","unstructured":"Virtanen P, Gommers R, Oliphant TE, Haberland M, Reddy T, Cournapeau D, et al. SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat Methods. 2020;17(3):261\u201372. https:\/\/doi.org\/10.1038\/s41592-019-0686-2.","journal-title":"Nat Methods"},{"key":"2538_CR118","doi-asserted-by":"publisher","unstructured":"Seabold S, Perktold J. Statsmodels: Econometric and statistical modeling with python. Proceedings of the 9th Python in Science Conference. https:\/\/doi.org\/10.25080\/Majora-92bf1922-011.","DOI":"10.25080\/Majora-92bf1922-011"},{"key":"2538_CR119","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1002\/spe.4380211102","volume":"21","author":"TMJ Fruchterman","year":"1991","unstructured":"Fruchterman TMJ, Reingold EM. Graph drawing by force-directed placement. Softw Pract Exp. 1991;21:1129\u201364. Available from:. https:\/\/doi.org\/10.1002\/spe.4380211102.","journal-title":"Softw Pract Exp"},{"issue":"51","key":"2538_CR120","doi-asserted-by":"publisher","first-page":"E5593","DOI":"10.1073\/pnas.1419161111","volume":"111","author":"S Shen","year":"2014","unstructured":"Shen S, Park JW, Lu Z-X, Lin L, Henry MD, Wu YN, et al. rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data. Proc Natl Acad Sci U S A. 2014;111(51):E5593\u2013601.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2538_CR121","doi-asserted-by":"publisher","unstructured":"Sterne-Weiler T, Weatheritt RJ, Best A, Ha KCH. Whippet: an efficient method for the detection and quantification of 944 alternative splicing reveals extensive transcriptomic complexity. bioRxiv. 2017. https:\/\/doi.org\/10.1101\/158519","DOI":"10.1101\/158519"},{"key":"2538_CR122","doi-asserted-by":"crossref","unstructured":"Louadi Z. NEASE: A network-based approach for the enrichment of alternative splicing events. Github. 2021. Available from: https:\/\/github.com\/louadi\/NEASE. Accessed 22 Nov 2021.","DOI":"10.1186\/s13059-021-02538-1"},{"key":"2538_CR123","doi-asserted-by":"publisher","unstructured":"Louadi Z. NEASE: v.1.1.6. Zenodo; 2021. Available from:. https:\/\/doi.org\/10.5281\/zenodo.5653490.","DOI":"10.5281\/zenodo.5653490"},{"key":"2538_CR124","doi-asserted-by":"publisher","unstructured":"Louadi Z. NEASE-tutorials: v1.2. Zenodo; 2021. Available from: https:\/\/doi.org\/10.5281\/ZENODO.5562626","DOI":"10.5281\/ZENODO.5562626"}],"container-title":["Genome Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13059-021-02538-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13059-021-02538-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13059-021-02538-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T11:11:20Z","timestamp":1726225880000},"score":1,"resource":{"primary":{"URL":"https:\/\/genomebiology.biomedcentral.com\/articles\/10.1186\/s13059-021-02538-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":124,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2538"],"URL":"https:\/\/doi.org\/10.1186\/s13059-021-02538-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.07.14.452376","asserted-by":"object"}]},"ISSN":["1474-760X"],"issn-type":[{"value":"1474-760X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"15 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"327"}}