{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T20:27:47Z","timestamp":1768595267755,"version":"3.49.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T00:00:00Z","timestamp":1572220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T00:00:00Z","timestamp":1572220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Orthology inference is normally based on full-length protein sequences. However, most proteins contain independently folding and recurring regions, domains. The domain architecture of a protein is vital for its function, and recombination events mean individual domains can have different evolutionary histories. It has previously been shown that orthologous proteins may differ in domain architecture, creating challenges for orthology inference methods operating on full-length sequences. We have developed Domainoid, a new tool aiming to overcome these challenges faced by full-length orthology methods by inferring orthology on the domain level. It employs the InParanoid algorithm on single domains separately, to infer groups of orthologous domains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This domain-oriented approach allows detection of discordant domain orthologs, cases where different domains on the same protein have different evolutionary histories. In addition to domain level analysis, protein level orthology based on the fraction of domains that are orthologous can be inferred. Domainoid orthology assignments were compared to those yielded by the conventional full-length approach InParanoid, and were validated in a standard benchmark.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results show that domain-based orthology inference can reveal many orthologous relationships that are not found by full-length sequence approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/bitbucket.org\/sonnhammergroup\/domainoid\/\">https:\/\/bitbucket.org\/sonnhammergroup\/domainoid\/<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1186\/s12859-019-3137-2","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T11:09:06Z","timestamp":1572260946000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Domainoid: domain-oriented orthology inference"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0532-8251","authenticated-orcid":false,"given":"Emma","family":"Persson","sequence":"first","affiliation":[]},{"given":"Mateusz","family":"Kaduk","sequence":"additional","affiliation":[]},{"given":"Sofia K.","family":"Forslund","sequence":"additional","affiliation":[]},{"given":"Erik L. L.","family":"Sonnhammer","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2019,10,28]]},"reference":[{"key":"3137_CR1","doi-asserted-by":"publisher","first-page":"99","DOI":"10.2307\/2412448","volume":"19","author":"WM Fitch","year":"1970","unstructured":"Fitch WM. Distinguishing homologous from analogous proteins. Syst Zool. 1970;19:99\u2013113.","journal-title":"Syst Zool"},{"key":"3137_CR2","doi-asserted-by":"publisher","first-page":"e1002514","DOI":"10.1371\/journal.pcbi.1002514","volume":"8","author":"AM Altenhoff","year":"2012","unstructured":"Altenhoff AM, Studer RA, Robinson-Rechavi M, Dessimoz C. Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs. PLoS Comput Biol. 2012;8:e1002514.","journal-title":"PLoS Comput Biol"},{"key":"3137_CR3","doi-asserted-by":"publisher","first-page":"D240","DOI":"10.1093\/nar\/gku1158","volume":"43","author":"AM Altenhoff","year":"2015","unstructured":"Altenhoff AM, \u0160kunca N, Glover N, Train C-M, Sueki A, Pili\u017eota I, et al. The OMA orthology database in 2015: function predictions, better plant support, synteny view and other improvements. Nucleic Acids Res. 2015;43:D240\u20139.","journal-title":"Nucleic Acids Res"},{"issue":"Database","key":"3137_CR4","doi-asserted-by":"publisher","first-page":"D250","DOI":"10.1093\/nar\/gkm796","volume":"36","author":"L. J. Jensen","year":"2007","unstructured":"Jensen LJ, Julien P, Kuhn M, von Mering C, Muller J, Doerks T, et al. eggNOG: automated construction and annotation of orthologous groups of genes. Nucleic Acids Res 2008;36: D250\u2013D254.","journal-title":"Nucleic Acids Research"},{"key":"3137_CR5","doi-asserted-by":"publisher","first-page":"D234","DOI":"10.1093\/nar\/gku1203","volume":"43","author":"ELL Sonnhammer","year":"2015","unstructured":"Sonnhammer ELL, \u00d6stlund G. InParanoid 8: orthology analysis between 273 proteomes, mostly eukaryotic. Nucleic Acids Res. 2015;43:D234\u20139.","journal-title":"Nucleic Acids Res"},{"key":"3137_CR6","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1093\/bioinformatics\/btw774","volume":"33","author":"M Kaduk","year":"2017","unstructured":"Kaduk M, Sonnhammer E. Improved orthology inference with Hieranoid 2. Bioinformatics. 2017;33:1154\u20139.","journal-title":"Bioinformatics"},{"key":"3137_CR7","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1093\/molbev\/msm254","volume":"25","author":"K Forslund","year":"2008","unstructured":"Forslund K, Henricson A, Hollich V, Sonnhammer ELL. Domain tree-based analysis of protein architecture evolution. Mol Biol Evol. 2008;25:254\u201364.","journal-title":"Mol Biol Evol"},{"key":"3137_CR8","doi-asserted-by":"publisher","first-page":"2993","DOI":"10.1093\/bioinformatics\/btu492","volume":"30","author":"ELL Sonnhammer","year":"2014","unstructured":"Sonnhammer ELL. Gabald\u00f3n T, Sousa da Silva AW, Martin M, Robinson-Rechavi M, Boeckmann B, et al. big data and other challenges in the quest for orthologs. Bioinformatics. 2014;30:2993\u20138.","journal-title":"Bioinformatics"},{"key":"3137_CR9","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1038\/nrg3456","volume":"14","author":"T Gabald\u00f3n","year":"2013","unstructured":"Gabald\u00f3n T, Koonin EV. Functional and evolutionary implications of gene orthology. Nat Rev Genet. 2013;14:360\u20136.","journal-title":"Nat Rev Genet"},{"key":"3137_CR10","first-page":"55","volume":"1","author":"MY Galperin","year":"1998","unstructured":"Galperin MY, Koonin EV. Sources of systematic error in functional annotation of genomes: domain rearrangement, non-orthologous gene displacement and operon disruption. In Silico Biol. 1998;1:55\u201367.","journal-title":"In Silico Biol"},{"key":"3137_CR11","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1186\/1471-2105-12-326","volume":"12","author":"K Forslund","year":"2011","unstructured":"Forslund K, Pekkari I, Sonnhammer ELL. Domain architecture conservation in orthologs. BMC Bioinformatics. 2011;12:326.","journal-title":"BMC Bioinformatics"},{"key":"3137_CR12","doi-asserted-by":"publisher","first-page":"D343","DOI":"10.1093\/nar\/gkl978","volume":"35","author":"I Uchiyama","year":"2007","unstructured":"Uchiyama I. MBGD: a platform for microbial comparative genomics based on the automated construction of orthologous groups. Nucleic Acids Res. 2007;35:D343\u20136.","journal-title":"Nucleic Acids Res"},{"key":"3137_CR13","doi-asserted-by":"publisher","first-page":"D279","DOI":"10.1093\/nar\/gkv1344","volume":"44","author":"RD Finn","year":"2016","unstructured":"Finn RD, Coggill P, Eberhardt RY, Eddy SR, Mistry J, Mitchell AL, et al. The Pfam protein families database: towards a more sustainable future. Nucleic Acids Res. 2016;44:D279\u201385.","journal-title":"Nucleic Acids Res"},{"key":"3137_CR14","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/j.jmb.2005.08.067","volume":"353","author":"\u00c5K Bj\u00f6rklund","year":"2005","unstructured":"Bj\u00f6rklund \u00c5K, Ekman D, Light S, Frey-Sk\u00f6tt J, Elofsson A. Domain rearrangements in protein evolution. J Mol Biol. 2005;353:911\u201323.","journal-title":"J Mol Biol"},{"key":"3137_CR15","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1089\/cmb.2007.A009","volume":"14","author":"N Song","year":"2007","unstructured":"Song N, Sedgewick RD, Durand D. Domain architecture comparison for multidomain homology identification. J Comput Biol. 2007;14:496\u2013516.","journal-title":"J Comput Biol"},{"key":"3137_CR16","doi-asserted-by":"publisher","first-page":"e1000063","DOI":"10.1371\/journal.pcbi.1000063","volume":"4","author":"N Song","year":"2008","unstructured":"Song N, Joseph JM, Davis GB, Durand D. Sequence similarity network reveals common ancestry of multidomain proteins. PLoS Comput Biol. 2008;4:e1000063.","journal-title":"PLoS Comput Biol"},{"key":"3137_CR17","doi-asserted-by":"publisher","first-page":"D270","DOI":"10.1093\/nar\/gku1152","volume":"43","author":"I Uchiyama","year":"2015","unstructured":"Uchiyama I, Mihara M, Nishide H, Chiba H. MBGD update 2015: microbial genome database for flexible ortholog analysis utilizing a diverse set of genomic data. Nucleic Acids Res. 2015;43:D270\u20136.","journal-title":"Nucleic Acids Res"},{"key":"3137_CR18","doi-asserted-by":"publisher","first-page":"W84","DOI":"10.1093\/nar\/gkp373","volume":"37","author":"RS Datta","year":"2009","unstructured":"Datta RS, Meacham C, Samad B, Neyer C, Sj\u00f6lander K. Berkeley PHOG: PhyloFacts orthology group prediction web server. Nucleic Acids Res. 2009;37:W84\u20139.","journal-title":"Nucleic Acids Res"},{"key":"3137_CR19","doi-asserted-by":"crossref","unstructured":"Chen T-W, Wu TH, Ng WV, Lin W-C. DODO: an efficient orthologous genes assignment tool based on domain architectures. Domain based ortholog detection. BMC Bioinformatics 2010;11 Suppl 7: S6.","DOI":"10.1186\/1471-2105-11-S7-S6"},{"key":"3137_CR20","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1186\/s12859-015-0570-8","volume":"16","author":"T Bitard-Feildel","year":"2015","unstructured":"Bitard-Feildel T, Kemena C, Greenwood JM, Bornberg-Bauer E. Domain similarity based orthology detection. BMC Bioinformatics. 2015;16:154.","journal-title":"BMC Bioinformatics"},{"key":"3137_CR21","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1007\/s11103-006-9101-3","volume":"63","author":"MR Islam","year":"2007","unstructured":"Islam MR, Kim H, Kang S-W, Kim J-S, Jeong Y-M, Hwang H-J, et al. Functional characterization of a gene encoding a dual domain for uridine kinase and uracil phosphoribosyltransferase in Arabidopsis thaliana. Plant Mol Biol. 2007;63:465\u201377.","journal-title":"Plant Mol Biol"},{"key":"3137_CR22","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1038\/nmeth.3830","volume":"13","author":"AM Altenhoff","year":"2016","unstructured":"Altenhoff AM, Boeckmann B, Capella-Gutierrez S, Dalquen DA, DeLuca T, Forslund K, et al. Standardized benchmarking in the quest for orthologs. Nat Methods. 2016;13:425\u201330.","journal-title":"Nat Methods"},{"issue":"3","key":"3137_CR23","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","volume":"215","author":"Stephen F. Altschul","year":"1990","unstructured":"Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol 1990:403\u201310. https:\/\/doi.org\/10.1016\/s0022-2836(05)80360-2 .","journal-title":"Journal of Molecular Biology"},{"key":"3137_CR24","unstructured":"Sheridan C. The Python language reference manual. Morrisville: Lulu Press, Inc; 2016."},{"key":"3137_CR25","unstructured":"Wall L, others. Perl Language Reference Manual: For Perl Version 5.12.1. Bristol: Network Theory ltd; 2010."},{"key":"3137_CR26","doi-asserted-by":"publisher","first-page":"e1002195","DOI":"10.1371\/journal.pcbi.1002195","volume":"7","author":"SR Eddy","year":"2011","unstructured":"Eddy SR. Accelerated profile HMM searches. PLoS Comput Biol. 2011;7:e1002195.","journal-title":"PLoS Comput Biol"},{"issue":"5","key":"3137_CR27","doi-asserted-by":"publisher","first-page":"e0177459","DOI":"10.1371\/journal.pone.0177459","volume":"12","author":"Gregory M. Kurtzer","year":"2017","unstructured":"Kurtzer GM, Sochat V, Bauer MW. Singularity: Scientific containers for mobility of compute. PLoS One. 2017:e0177459. https:\/\/doi.org\/10.1371\/journal.pone.0177459","journal-title":"PLOS ONE"},{"key":"3137_CR28","doi-asserted-by":"publisher","first-page":"D476","DOI":"10.1093\/nar\/gki107","volume":"33","author":"KP O\u2019Brien","year":"2004","unstructured":"O\u2019Brien KP. Inparanoid: a comprehensive database of eukaryotic orthologs. Nucleic Acids Res. 2004;33:D476\u201380.","journal-title":"Nucleic Acids Res"},{"key":"3137_CR29","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1093\/bioinformatics\/bts050","volume":"28","author":"C Dessimoz","year":"2012","unstructured":"Dessimoz C, Gabald\u00f3n T, Roos DS, Sonnhammer ELL, Herrero J. Quest for Orthologs consortium. Toward community standards in the quest for orthologs. Bioinformatics. 2012;28:900\u20134.","journal-title":"Bioinformatics"},{"key":"3137_CR30","doi-asserted-by":"publisher","first-page":"D222","DOI":"10.1093\/nar\/gkt1223","volume":"42","author":"RD Finn","year":"2014","unstructured":"Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, et al. Pfam: the protein families database. Nucleic Acids Res. 2014;42:D222\u201330.","journal-title":"Nucleic Acids Res"},{"key":"3137_CR31","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1093\/nar\/gkh340","volume":"32","author":"RC Edgar","year":"2004","unstructured":"Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004;32:1792\u20137.","journal-title":"Nucleic Acids Res"},{"key":"3137_CR32","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/1471-2105-6-108","volume":"6","author":"ELL Sonnhammer","year":"2005","unstructured":"Sonnhammer ELL, Hollich V. Scoredist: a simple and robust protein sequence distance estimator. BMC Bioinformatics. 2005;6:108.","journal-title":"BMC Bioinformatics"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-019-3137-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12859-019-3137-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-019-3137-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T05:48:19Z","timestamp":1695361699000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-019-3137-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,28]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["3137"],"URL":"https:\/\/doi.org\/10.1186\/s12859-019-3137-2","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,28]]},"assertion":[{"value":"20 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"523"}}