{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T18:42:40Z","timestamp":1774550560922,"version":"3.50.1"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"D1","license":[{"start":{"date-parts":[[2016,10,4]],"date-time":"2016-10-04T00:00:00Z","timestamp":1475539200000},"content-version":"vor","delay-in-days":1417,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,1,1]]},"DOI":"10.1093\/nar\/gks1058","type":"journal-article","created":{"date-parts":[[2012,11,18]],"date-time":"2012-11-18T20:40:01Z","timestamp":1353271201000},"page":"D110-D117","source":"Crossref","is-referenced-by-count":226,"title":["APPRIS: annotation of principal and alternative splice isoforms"],"prefix":"10.1093","volume":"41","author":[{"given":"Jose Manuel","family":"Rodriguez","sequence":"first","affiliation":[]},{"given":"Paolo","family":"Maietta","sequence":"additional","affiliation":[]},{"given":"Iakes","family":"Ezkurdia","sequence":"additional","affiliation":[]},{"given":"Alessandro","family":"Pietrelli","sequence":"additional","affiliation":[]},{"given":"Jan-Jaap","family":"Wesselink","sequence":"additional","affiliation":[]},{"given":"Gonzalo","family":"Lopez","sequence":"additional","affiliation":[]},{"given":"Alfonso","family":"Valencia","sequence":"additional","affiliation":[]},{"given":"Michael L.","family":"Tress","sequence":"additional","affiliation":[]}],"member":"286","published-online":{"date-parts":[[2012,11,17]]},"reference":[{"key":"key\n\t\t\t\t20171013035642_gks1058-B1","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1101\/SQB.1987.052.01.098","article-title":"The exon theory of genes","volume":"52","author":"Gilbert","year":"1987","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B2","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0092-8674(00)00128-8","article-title":"Protein diversity from alternative splicing: a challenge for bioinformatics and post-genome biology","volume":"103","author":"Black","year":"2000","journal-title":"Cell"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B3","doi-asserted-by":"crossref","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":"key\n\t\t\t\t20171013035642_gks1058-B4","doi-asserted-by":"crossref","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":"key\n\t\t\t\t20171013035642_gks1058-B5","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1042\/BST0381615","article-title":"Cutting the nonsense: the degradation of PTC-containing mRNAs","volume":"38","author":"Nicholson","year":"2010","journal-title":"Biochem. Soc. Trans."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B6","doi-asserted-by":"crossref","first-page":"R35","DOI":"10.1186\/gb-2012-13-5-r35","article-title":"Mammalian tissues defective in nonsense-mediated mRNA decay display highly aberrant splicing patterns","volume":"13","author":"Weischenfeldt","year":"2012","journal-title":"Genome Biol."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B7","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1002\/bies.10153","article-title":"Non-stop decay\u2014a new mRNA surveillance pathway","volume":"24","author":"Vasudevan","year":"2002","journal-title":"Bioessays"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B8","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/wrna.17","article-title":"No-go decay: a quality control mechanism for RNA in translation","volume":"1","author":"Harigaya","year":"2010","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B9","doi-asserted-by":"crossref","first-page":"5495","DOI":"10.1073\/pnas.0700800104","article-title":"The implications of alternative splicing in the ENCODE protein complement","volume":"104","author":"Tress","year":"2007","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B10","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S0968-0004(00)01604-2","article-title":"Alternative pre-mRNA splicing: the logic of combinatorial control","volume":"25","author":"Smith","year":"2000","journal-title":"Trends Biochem. Sci."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B11","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1093\/molbev\/msr127","article-title":"The origins, evolution, and functional potential of alternative splicing in vertebrates","volume":"28","author":"Mudge","year":"2011","journal-title":"Mol. Biol. Evol."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B12","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/nature05874","article-title":"Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project","volume":"447","author":"Stamatoyannopoulos","year":"2007","journal-title":"Nature"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B13","doi-asserted-by":"crossref","first-page":"bas014","DOI":"10.1093\/database\/bas014","article-title":"The importance of identifying alternative splicing in vertebrate genome annotation","volume":"2012","author":"Frankish","year":"2012","journal-title":"Database"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B14","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1101\/gr.135350.111","article-title":"GENCODE: the reference annotation for the ENCODE Project","volume":"22","author":"Harrow","year":"2012","journal-title":"Genome Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B15","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","author":"ENCODE Project Consortium, Bernstein,B.E., Birney,E., Dunham,I., Green,E.D., Gunter,C. and Snyder,M.","year":"2012","journal-title":"Nature"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B16","doi-asserted-by":"crossref","first-page":"D84","DOI":"10.1093\/nar\/gkr991","article-title":"Ensembl 2012","volume":"40","author":"Flicek","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B17","doi-asserted-by":"crossref","first-page":"D71","DOI":"10.1093\/nar\/gkr981","article-title":"Reorganizing the protein space at the Universal Protein Resource","volume":"40","author":"UniProt Consortium","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/bioinformatics\/btm547","article-title":"Determination and validation of principal gene products","volume":"24","author":"Tress","year":"2008","journal-title":"Bioinformatics"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B19","doi-asserted-by":"crossref","first-page":"W235","DOI":"10.1093\/nar\/gkr437","article-title":"firestar\u2014advances in the prediction of functionally important residues","volume":"39","author":"Lopez","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B20","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1093\/nar\/gkq1021","article-title":"The RCSB Protein Data Bank: redesigned web site and web services","volume":"39","author":"Rose","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B21","doi-asserted-by":"crossref","first-page":"D290","DOI":"10.1093\/nar\/gkr1065","article-title":"The Pfam protein families database","volume":"40","author":"Punta","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B22","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1534\/genetics.104.032144","article-title":"Detecting amino acid sites under positive selection and purifying selection","volume":"169","author":"Massingham","year":"2005","journal-title":"Genetics"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B23","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1101\/gr.1933104","article-title":"Aligning multiple genomic sequences with the threaded blockset aligner","volume":"14","author":"Blanchette","year":"2004","journal-title":"Genome Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B24","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/1471-2105-6-298","article-title":"Kalign\u2014an accurate and fast multiple sequence alignment algorithm","volume":"6","author":"Lassmannm","year":"2005","journal-title":"BMC Bioinformatics"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B25","doi-asserted-by":"crossref","first-page":"10557","DOI":"10.1073\/pnas.0409137102","article-title":"An algorithm for progressive multiple alignment of sequences with insertions","volume":"102","author":"L\u00f6ytynoja","year":"2005","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B26","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/nprot.2007.131","article-title":"Locating proteins in the cell using TargetP, SignalP and related tools","volume":"2","author":"Emanuelsson","year":"2007","journal-title":"Nat. Protoc."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B27","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1093\/bioinformatics\/btl677","article-title":"Improving the accuracy of transmembrane protein topology prediction using evolutionary information","volume":"23","author":"Jones","year":"2007","journal-title":"Bioinformatics"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B28","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.jmb.2004.03.016","article-title":"A combined transmembrane topology and signal peptide prediction method","volume":"338","author":"K\u00e4ll","year":"2004","journal-title":"J. Mol. Biol."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B29","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1110\/ps.04625404","article-title":"Best alpha-helical transmembrane protein topology predictions are achieved using hidden Markov models and evolutionary information","volume":"13","author":"Viklund","year":"2004","journal-title":"Protein Sci."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B30","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1471-2105-6-31","article-title":"Automated generation of heuristics for biological sequence comparison","volume":"6","author":"Slater","year":"2005","journal-title":"BMC Bioinformatics"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B31","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B32","doi-asserted-by":"crossref","first-page":"R162","DOI":"10.1186\/gb-2008-9-11-r162","article-title":"Proteomics studies confirm the presence of alternative protein isoforms on a large scale","volume":"9","author":"Tress","year":"2008","journal-title":"Genome Biol."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B33","doi-asserted-by":"crossref","first-page":"21034","DOI":"10.1073\/pnas.0811066106","article-title":"Discovery and revision of Arabidopsis genes by proteogenomics","volume":"105","author":"Castellana","year":"2008","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B34","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1021\/pr900602d","article-title":"Detection of alternative splice variants at the proteome level in Aspergillus flavus","volume":"9","author":"Chang","year":"2010","journal-title":"J. Proteome Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B35","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/1471-2229-11-82","article-title":"Assessing the contribution of alternative splicing to proteome diversity in Arabidopsis thaliana using proteomics data","volume":"11","author":"Severing","year":"2011","journal-title":"BMC Plant Biol."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B36","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1101\/gr.114272.110","article-title":"Shotgun proteomics aids discovery of novel protein-coding genes, alternative splicing, and \u201cresurrected\u201d pseudogenes in the mouse genome","volume":"21","author":"Brosch","year":"2011","journal-title":"Genome Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B37","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1093\/molbev\/mss100","article-title":"Comparative proteomics reveals a significant bias towards alternative protein isoforms with conserved structure and function","volume":"29","author":"Ezkurdia","year":"2012","journal-title":"Mol. Biol. Evol."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B38","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1261\/rna.325107","article-title":"Global analysis of exon creation versus loss and the role of alternative splicing in 17 vertebrate genomes","volume":"13","author":"Alekseyenko","year":"2007","journal-title":"RNA"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B39","doi-asserted-by":"crossref","first-page":"D918","DOI":"10.1093\/nar\/gkr1055","article-title":"The UCSC Genome Browser database: extensions and updates 2011","volume":"40","author":"Dreszer","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B40","doi-asserted-by":"crossref","first-page":"R9","DOI":"10.1186\/gb-2004-6-1-r9","article-title":"Integration with the human genome of peptide sequences obtained by high-throughput mass spectrometry","volume":"6","author":"Desiere","year":"2005","journal-title":"Genome Biol."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B41","doi-asserted-by":"crossref","first-page":"bar049","DOI":"10.1093\/database\/bar049","article-title":"BioMart: driving a paradigm change in biological data management","volume":"2011","author":"Kasprzyk","year":"2011","journal-title":"Database"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B42","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1101\/gr.080531.108","article-title":"The consensus coding sequence (CCDS) project: identifying a common protein-coding gene set for the human and mouse genomes","volume":"19","author":"Harte","year":"2009","journal-title":"Genome Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B43","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1002\/stem.723","article-title":"TAp63 is important for cardiac differentiation of embryonic stem cells and heart development","volume":"29","author":"Rouleau","year":"2011","journal-title":"Stem Cells"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B44","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1146\/annurev-pathol-121808-102117","article-title":"p63 in epithelial survival, germ cell surveillance, and neoplasia","volume":"5","author":"Crum","year":"2010","journal-title":"Annu. Rev. Pathol."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B45","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1186\/1471-2105-11-216","article-title":"TassDB2\u2014a comprehensive database of subtle alternative splicing events","volume":"11","author":"Sinha","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B46","doi-asserted-by":"crossref","first-page":"D63","DOI":"10.1093\/nar\/gkm793","article-title":"ProSAS: a database for analyzing alternative splicing in the context of protein structures","volume":"36","author":"Birzele","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B47","doi-asserted-by":"crossref","first-page":"D305","DOI":"10.1093\/nar\/gkn869","article-title":"AS-ALPS: a database for analyzing the effects of alternative splicing on protein structure, interaction and network in human and mouse","volume":"37","author":"Shionyu","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B48","doi-asserted-by":"crossref","first-page":"D80","DOI":"10.1093\/nar\/gkq1073","article-title":"ASPicDB: a database of annotated transcript and protein variants generated by alternative splicing","volume":"39","author":"Martelli","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B49","doi-asserted-by":"crossref","first-page":"D735","DOI":"10.1093\/nar\/gkm1005","article-title":"TreeFam: 2008 Update","volume":"36","author":"Ruan","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B50","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":"key\n\t\t\t\t20171013035642_gks1058-B51","doi-asserted-by":"crossref","first-page":"W573","DOI":"10.1093\/nar\/gkm297","article-title":"firestar\u2014prediction of functionally important residues using structural templates and alignment reliability","volume":"35","author":"L\u00f3pez","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B52","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"Edgar","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B53","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1093\/nar\/gki328","article-title":"Comparative gene finding in chicken indicates that we are closing in on the set of multi-exonic widely expressed human genes","volume":"33","author":"Castelo","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B54","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nmeth.1818","article-title":"HHblits: lightning-fast iterative protein sequence searching by HMM\u2013HMM alignment","volume":"9","author":"Remmert","year":"2011","journal-title":"Nat. Methods"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B55","doi-asserted-by":"crossref","first-page":"D217","DOI":"10.1093\/nar\/gkl897","article-title":"FireDB\u2014a database of functionally important residues from proteins of known structure","volume":"35","author":"L\u00f3pez","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B56","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1093\/bioinformatics\/bth032","article-title":"SQUARE\u2014determining reliable regions in sequence alignments","volume":"20","author":"Tress","year":"2004","journal-title":"Bioinformatics"},{"key":"key\n\t\t\t\t20171013035642_gks1058-B57","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1006\/jsbi.2001.4335","article-title":"Fold change in evolution of protein structures","volume":"134","author":"Grishin","year":"2001","journal-title":"J. Struct. Biol."},{"key":"key\n\t\t\t\t20171013035642_gks1058-B58","doi-asserted-by":"crossref","first-page":"D655","DOI":"10.1093\/nar\/gkj040","article-title":"The PeptideAtlas project","volume":"34","author":"Desiere","year":"2006","journal-title":"Nucleic Acids Res."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/41\/D1\/D110\/18785919\/gks1058.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,7,5]],"date-time":"2019-07-05T15:07:49Z","timestamp":1562339269000},"score":1,"resource":{"primary":{"URL":"http:\/\/academic.oup.com\/nar\/article\/41\/D1\/D110\/1054030\/APPRIS-annotation-of-principal-and-alternative"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,17]]},"references-count":58,"journal-issue":{"issue":"D1","published-online":{"date-parts":[[2012,11,17]]},"published-print":{"date-parts":[[2013,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gks1058","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,1,1]]},"published":{"date-parts":[[2012,11,17]]}}}