{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:06Z","timestamp":1772138046823,"version":"3.50.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"20","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-LM011297"],"award-info":[{"award-number":["R01-LM011297"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35-GM128938"],"award-info":[{"award-number":["R35-GM128938"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Access to large-scale genomics and transcriptomics data from various tissues and cell lines allowed the discovery of wide-spread alternative splicing events and alternative promoter usage in mammalians. Between human and mouse, gene-level orthology is currently present for nearly 16k protein-coding genes spanning a diverse repertoire of over 200k total transcript isoforms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we describe a novel method, ExTraMapper, which leverages sequence conservation between exons of a pair of organisms and identifies a fine-scale orthology mapping at the exon and then transcript level. ExTraMapper identifies more than 350k exon mappings, as well as 30k transcript mappings between human and mouse using only sequence and gene annotation information. We demonstrate that ExTraMapper identifies a larger number of exon and transcript mappings compared to previous methods. Further, it identifies exon fusions, splits and losses due to splice site mutations, and finds mappings between microexons that are previously missed. By reanalysis of RNA-seq data from 13 matched human and mouse tissues, we show that ExTraMapper improves the correlation of transcript-specific expression levels suggesting a more accurate mapping of human and mouse transcripts. We also applied the method to detect conserved exon and transcript pairs between human and rhesus macaque genomes to highlight the point that ExTraMapper is applicable to any pair of organisms that have orthologous gene pairs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The source code and the results are available at https:\/\/github.com\/ay-lab\/ExTraMapper and http:\/\/ay-lab-tools.lji.org\/extramapper.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab393","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T15:36:11Z","timestamp":1621438571000},"page":"3412-3420","source":"Crossref","is-referenced-by-count":2,"title":["ExTraMapper: exon- and transcript-level mappings for orthologous gene pairs"],"prefix":"10.1093","volume":"37","author":[{"given":"Abhijit","family":"Chakraborty","sequence":"first","affiliation":[{"name":"Centers for Cancer Immunotherapy and Autoimmunity, La Jolla Institute for Immunology , La Jolla, CA 92037, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0708-6914","authenticated-orcid":false,"given":"Ferhat","family":"Ay","sequence":"additional","affiliation":[{"name":"Centers for Cancer Immunotherapy and Autoimmunity, La Jolla Institute for Immunology , La Jolla, CA 92037, USA"},{"name":"Department of Pediatrics, UC San Diego\u2014School of Medicine , La Jolla, CA 92093, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7053-1064","authenticated-orcid":false,"given":"Ramana V","family":"Davuluri","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Stony Brook University , Stony Brook, NY 11794, USA"}]}],"member":"286","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"2023051609053715800_btab393-B1","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":"2023051609053715800_btab393-B2","doi-asserted-by":"crossref","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol"},{"key":"2023051609053715800_btab393-B3","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1096\/fasebj.10.4.8647344","article-title":"Regulation of gene expression by alternative promoters","volume":"10","author":"Ayoubi","year":"1996","journal-title":"FASEB J"},{"key":"2023051609053715800_btab393-B4","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":"2023051609053715800_btab393-B5","doi-asserted-by":"publisher","author":"Blekhman","year":"2012","DOI":"10.1038\/npre.2012.7054.1"},{"key":"2023051609053715800_btab393-B6","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nature00766","article-title":"Mutations of the BRAF gene in human cancer","volume":"417","author":"Davies","year":"2002","journal-title":"Nature"},{"key":"2023051609053715800_btab393-B7","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.tig.2008.01.008","article-title":"The functional consequences of alternative promoter use in mammalian genomes","volume":"24","author":"Davuluri","year":"2008","journal-title":"Trends Genet"},{"key":"2023051609053715800_btab393-B8","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1093\/molbev\/msu132","article-title":"OrthoMaM v8: a database of orthologous exons and coding sequences for comparative genomics in mammals","volume":"31","author":"Douzery","year":"2014","journal-title":"Mol. Biol. Evol"},{"key":"2023051609053715800_btab393-B9","doi-asserted-by":"crossref","first-page":"D749","DOI":"10.1093\/nar\/gkt1196","article-title":"Ensembl 2014","volume":"42","author":"Flicek","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2023051609053715800_btab393-B10","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1186\/1471-2164-13-S1-S10","article-title":"Identification of gene-oriented exon orthology between human and mouse","volume":"13","author":"Fu","year":"2012","journal-title":"BMC Genomics"},{"key":"2023051609053715800_btab393-B11","doi-asserted-by":"crossref","first-page":"121","DOI":"10.12688\/f1000research.6536.1","article-title":"A reanalysis of mouse ENCODE comparative gene expression data","volume":"4","author":"Gilad","year":"2015","journal-title":"F1000Res"},{"key":"2023051609053715800_btab393-B12","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.sjbs.2014.10.002","article-title":"BRAF gene: from human cancers to developmental syndromes","volume":"22","author":"Hussain","year":"2015","journal-title":"Saudi J. Biol. Sci"},{"key":"2023051609053715800_btab393-B13","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.cell.2014.11.035","article-title":"A highly conserved program of neuronal microexons is misregulated in autistic brains","volume":"159","author":"Irimia","year":"2014","journal-title":"Cell"},{"key":"2023051609053715800_btab393-B14","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: a fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"2023051609053715800_btab393-B15","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1186\/1471-2105-12-305","article-title":"IsoformEx: isoform level gene expression estimation using weighted non-negative least squares from mRNA-Seq data","volume":"12","author":"Kim","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2023051609053715800_btab393-B16","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1146\/annurev-immunol-041015-055427","article-title":"Retinoic acid and retinoic acid receptors as pleiotropic modulators of the immune system","volume":"34","author":"Larange","year":"2016","journal-title":"Annu. Rev. Immunol"},{"key":"2023051609053715800_btab393-B17","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1093\/bioinformatics\/bts034","article-title":"The SVA package for removing batch effects and other unwanted variation in high-throughput experiments","volume":"28","author":"Leek","year":"2012","journal-title":"Bioinformatics"},{"key":"2023051609053715800_btab393-B18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1146\/annurev-genet-110711-155437","article-title":"Disentangling the many layers of eukaryotic transcriptional regulation","volume":"46","author":"Lelli","year":"2012","journal-title":"Annu. Rev. Genet"},{"key":"2023051609053715800_btab393-B19","doi-asserted-by":"crossref","first-page":"e30417","DOI":"10.1371\/journal.pone.0030417","article-title":"Isoform diversity and regulation in peripheral and central neurons revealed through RNA-Seq","volume":"7","author":"Lerch","year":"2012","journal-title":"PLoS One"},{"key":"2023051609053715800_btab393-B20","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/j.1460-2075.1991.tb07921.x","article-title":"Multiple isoforms of the mouse retinoic acid receptor alpha are generated by alternative splicing and differential induction by retinoic acid","volume":"10","author":"Leroy","year":"1991","journal-title":"EMBO J"},{"key":"2023051609053715800_btab393-B21","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"2023051609053715800_btab393-B22","doi-asserted-by":"crossref","first-page":"17224","DOI":"10.1073\/pnas.1413624111","article-title":"Comparison of the transcriptional landscapes between human and mouse tissues","volume":"111","author":"Lin","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051609053715800_btab393-B23","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/nrm1645","article-title":"Understanding alternative splicing: towards a cellular code","volume":"6","author":"Matlin","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"2023051609053715800_btab393-B24","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/ng1159","article-title":"Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and\/or loss","volume":"34","author":"Modrek","year":"2003","journal-title":"Nat. Genet"},{"key":"2023051609053715800_btab393-B25","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/sj.cdd.4401914","article-title":"p53\/p63\/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress","volume":"13","author":"Murray-Zmijewski","year":"2006","journal-title":"Cell Death Differ"},{"key":"2023051609053715800_btab393-B26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-0992-6_1","article-title":"Genome-wide mapping of RNA Pol-II promoter usage in mouse tissues by ChIP-seq","volume":"1176","author":"Pal","year":"2014","journal-title":"Methods Mol. Biol"},{"key":"2023051609053715800_btab393-B27","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkn153","article-title":"Exalign: a new method for comparative analysis of exon-intron gene structures","volume":"36","author":"Pavesi","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"2023051609053715800_btab393-B28","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.mcn.2017.10.006","article-title":"Neuron-specific alternative splicing of transcriptional machineries: implications for neurodevelopmental disorders","volume":"87","author":"Porter","year":"2018","journal-title":"Mol. Cell Neurosci"},{"key":"2023051609053715800_btab393-B29","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.molcel.2016.11.033","article-title":"Misregulation of an activity-dependent splicing network as a common mechanism underlying autism spectrum disorders","volume":"64","author":"Quesnel-Vallieres","year":"2016","journal-title":"Mol. Cell"},{"key":"2023051609053715800_btab393-B30","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"2023051609053715800_btab393-B31","doi-asserted-by":"crossref","first-page":"273","DOI":"10.15252\/embj.201490651","article-title":"Microexons\u2013tiny but mighty","volume":"34","author":"Scheckel","year":"2015","journal-title":"EMBO J"},{"key":"2023051609053715800_btab393-B32","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1146\/annurev.ge.21.120187.001321","article-title":"Alternative promoters in developmental gene expression","volume":"21","author":"Schibler","year":"1987","journal-title":"Annu. Rev. Genet"},{"key":"2023051609053715800_btab393-B33","doi-asserted-by":"crossref","first-page":"7911","DOI":"10.1523\/JNEUROSCI.5313-06.2007","article-title":"ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration","volume":"27","author":"Seijffers","year":"2007","journal-title":"J. Neurosci"},{"key":"2023051609053715800_btab393-B34","doi-asserted-by":"crossref","first-page":"15776","DOI":"10.1073\/pnas.2136655100","article-title":"Cap analysis gene expression for high-throughput analysis of transcriptional starting point and identification of promoter usage","volume":"100","author":"Shiraki","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051609053715800_btab393-B35","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1101\/gr.3715005","article-title":"Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes","volume":"15","author":"Siepel","year":"2005","journal-title":"Genome Res"},{"key":"2023051609053715800_btab393-B36","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1089\/1066527041410472","article-title":"Combining phylogenetic and hidden Markov models in biosequence analysis","volume":"11","author":"Siepel","year":"2004","journal-title":"J. Comput. Biol"},{"key":"2023051609053715800_btab393-B37","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.gde.2009.04.001","article-title":"The RASopathies: developmental syndromes of Ras\/MAPK pathway dysregulation","volume":"19","author":"Tidyman","year":"2009","journal-title":"Curr. Opin. Genet. Dev"},{"key":"2023051609053715800_btab393-B38","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/bioinformatics\/btp120","article-title":"TopHat: discovering splice junctions with RNA-Seq","volume":"25","author":"Trapnell","year":"2009","journal-title":"Bioinformatics"},{"key":"2023051609053715800_btab393-B39","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrg2484","article-title":"RNA-Seq: a revolutionary tool for transcriptomics","volume":"10","author":"Wang","year":"2009","journal-title":"Nat. Rev. Genet"},{"key":"2023051609053715800_btab393-B40","doi-asserted-by":"crossref","first-page":"D710","DOI":"10.1093\/nar\/gkv1157","article-title":"Ensembl 2016","volume":"44","author":"Yates","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2023051609053715800_btab393-B41","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature13992","article-title":"A comparative encyclopedia of DNA elements in the mouse genome","volume":"515","author":"Yue","year":"2014","journal-title":"Nature"},{"key":"2023051609053715800_btab393-B42","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1186\/1471-2164-11-534","article-title":"Assessment of orthologous splicing isoforms in human and mouse orthologous genes","volume":"11","author":"Zambelli","year":"2010","journal-title":"BMC Genomics"},{"key":"2023051609053715800_btab393-B43","doi-asserted-by":"crossref","first-page":"R120","DOI":"10.1186\/gb-2009-10-11-r120","article-title":"Divergence of exonic splicing elements after gene duplication and the impact on gene structures","volume":"10","author":"Zhang","year":"2009","journal-title":"Genome Biol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btab393\/38600408\/btab393.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/20\/3412\/50338591\/btab393.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/20\/3412\/50338591\/btab393.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T05:12:14Z","timestamp":1684213934000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/37\/20\/3412\/6278896"}},"subtitle":[],"editor":[{"given":"Janet","family":"Kelso","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2021,5,20]]},"references-count":43,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2021,10,25]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btab393","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/277723","asserted-by":"object"}]},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,10,15]]},"published":{"date-parts":[[2021,5,20]]}}}