{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T02:54:14Z","timestamp":1771037654954,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"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\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2020YFC2004704"],"award-info":[{"award-number":["2020YFC2004704"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PKU-Baidu Fund","award":["2019BD014"],"award-info":[{"award-number":["2019BD014"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970440"],"award-info":[{"award-number":["81970440"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62025102"],"award-info":[{"award-number":["62025102"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81921001"],"award-info":[{"award-number":["81921001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82025008"],"award-info":[{"award-number":["82025008"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Peking University Basic Research Program","award":["BMU2020JC001"],"award-info":[{"award-number":["BMU2020JC001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Animal models have a certain degree of similarity with human in genes and physiological processes, which leads them to be valuable tools for studying human diseases and for assisting drug development. However, translational researches adopting animal models are largely restricted by the species heterogeneity, which is also a major reason for the failure of drug research. Currently, computational method for exploring the functional differences between orthologous genes is still insufficient. For this purpose, here, we presented an algorithm, functional divergence score (FDS), by comprehensively evaluating the functional differences between the microRNAs regulating the paired orthologous genes. Given that mouse is one of the most popular model animals, currently, FDS was designed to dissect the functional divergence of orthologous genes between human and mouse. The results showed that gene FDS value is significantly associated with gene evolutionary characteristics and can discover expression divergence of human\u2013mouse orthologous genes. Moreover, FDS performed well in distinguishing the targets of approved drugs and the failed ones. These results suggest that FDS is a valuable tool to evaluate the functional divergence of paired human and mouse orthologous genes. In addition, for each orthologous gene pair, FDS can provide detailed differences in functions and phenotypes. Our study provided a useful tool for quantifying the functional difference between human and mouse, and the presented framework is easily to be extended to the orthologous genes between human and other species. An online server of FDS is available at http:\/\/www.cuilab.cn\/fds\/.<\/jats:p>","DOI":"10.1093\/bib\/bbab253","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T19:12:47Z","timestamp":1623784367000},"source":"Crossref","is-referenced-by-count":4,"title":["Defining the functional divergence of orthologous genes between human and mouse in the context of miRNA regulation"],"prefix":"10.1093","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-5225","authenticated-orcid":false,"given":"Chunmei","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing, China"}]},{"given":"Yuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing, China"}]},{"given":"Qinghua","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing, China"}]}],"member":"286","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"2021110815081235300_ref1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1258\/jrsm.2007.070164","article-title":"Medical progress depends on animal models\u2014doesn\u2019t it?","volume":"101","author":"Matthews","year":"2008","journal-title":"J R Soc Med"},{"key":"2021110815081235300_ref2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/bs.mie.2018.01.008","article-title":"The mouse as a model organism for assessing anesthetic sensitivity","volume":"602","author":"Wasilczuk","year":"2018","journal-title":"Methods Enzymol"},{"key":"2021110815081235300_ref3","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4103\/0975-7406.124301","article-title":"Use of rodents as models of human diseases","volume":"6","author":"Vandamme","year":"2014","journal-title":"J Pharm Bioallied Sci"},{"key":"2021110815081235300_ref4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13024-017-0231-7","article-title":"Practical considerations for choosing a mouse model of Alzheimer\u2019s disease","volume":"12","author":"Jankowsky","year":"2017","journal-title":"Mol Neurodegener"},{"key":"2021110815081235300_ref5","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1165\/rcmb.2016-0177OC","article-title":"Development of a mouse model of metabolic syndrome, pulmonary hypertension, and heart failure with preserved ejection fraction","volume":"56","author":"Meng","year":"2017","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2021110815081235300_ref6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41568-019-0133-9","article-title":"Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data","volume":"19","author":"Rudin","year":"2019","journal-title":"Nat Rev Cancer"},{"key":"2021110815081235300_ref7","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.jhep.2018.06.009","article-title":"Mutational landscape of a chemically-induced mouse model of liver cancer","volume":"69","author":"Connor","year":"2018","journal-title":"J Hepatol"},{"key":"2021110815081235300_ref8","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.bcp.2013.08.006","article-title":"Animal models of human disease: challenges in enabling translation","volume":"87","author":"McGonigle","year":"2014","journal-title":"Biochem Pharmacol"},{"key":"2021110815081235300_ref9","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1083\/jcb.200606073","article-title":"The major human and mouse granzymes are structurally and functionally divergent","volume":"175","author":"Kaiserman","year":"2006","journal-title":"J Cell Biol"},{"key":"2021110815081235300_ref10","doi-asserted-by":"crossref","first-page":"9408","DOI":"10.1074\/jbc.M113.525808","article-title":"Identification of Serpinb6b as a species-specific mouse granzyme A inhibitor suggests functional divergence between human and mouse granzyme A","volume":"289","author":"Kaiserman","year":"2014","journal-title":"J Biol Chem"},{"key":"2021110815081235300_ref11","first-page":"114","article-title":"Lost in translation: animal models and clinical trials in cancer treatment","volume":"6","author":"Mak","year":"2014","journal-title":"Am J Transl Res"},{"key":"2021110815081235300_ref12","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1093\/molbev\/msy056","article-title":"Divergence of noncoding regulatory elements explains gene-phenotype differences between human and mouse orthologous genes","volume":"35","author":"Han","year":"2018","journal-title":"Mol Biol Evol"},{"key":"2021110815081235300_ref13","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1186\/s12862-015-0534-7","article-title":"A comparison of human and mouse gene co-expression networks reveals conservation and divergence at the tissue, pathway and disease levels","volume":"15","author":"Monaco","year":"2015","journal-title":"BMC Evol Biol"},{"key":"2021110815081235300_ref14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41580-018-0045-7","article-title":"Regulation of microRNA function in animals","volume":"20","author":"Gebert","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2021110815081235300_ref15","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1039\/c2mb05469h","article-title":"An upstream interacting context based framework for the computational inference of microRNA functions","volume":"8","author":"Qiu","year":"2012","journal-title":"Mol Biosyst"},{"key":"2021110815081235300_ref16","doi-asserted-by":"crossref","first-page":"D9","DOI":"10.1093\/nar\/gkz899","article-title":"Database resources of the National Center for Biotechnology Information","volume":"48","author":"Sayers","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2021110815081235300_ref17","doi-asserted-by":"crossref","first-page":"D853","DOI":"10.1093\/nar\/gky1095","article-title":"The UCSC Genome Browser database: 2019 update","volume":"47","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2021110815081235300_ref18","doi-asserted-by":"crossref","first-page":"D155","DOI":"10.1093\/nar\/gky1141","article-title":"miRBase: from microRNA sequences to function","volume":"47","author":"Kozomara","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2021110815081235300_ref19","doi-asserted-by":"crossref","first-page":"W180","DOI":"10.1093\/nar\/gky509","article-title":"TAM 2.0: tool for MicroRNA set analysis","volume":"46","author":"Li","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2021110815081235300_ref20","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"Elife"},{"key":"2021110815081235300_ref21","doi-asserted-by":"crossref","first-page":"D149","DOI":"10.1093\/nar\/gkm995","article-title":"The microRNA.org resource: targets and expression","volume":"36","author":"Betel","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"2021110815081235300_ref22","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1038\/ng2135","article-title":"The role of site accessibility in microRNA target recognition","volume":"39","author":"Kertesz","year":"2007","journal-title":"Nat Genet"},{"key":"2021110815081235300_ref23","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1093\/bioinformatics\/btl633","article-title":"Enrichment or depletion of a GO category within a class of genes: which test?","volume":"23","author":"Rivals","year":"2007","journal-title":"Bioinformatics"},{"key":"2021110815081235300_ref24","doi-asserted-by":"crossref","first-page":"D745","DOI":"10.1093\/nar\/gky1113","article-title":"Ensembl 2019","volume":"47","author":"Cunningham","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2021110815081235300_ref25","doi-asserted-by":"crossref","first-page":"D574","DOI":"10.1093\/nar\/gkt1131","article-title":"DEG 10, an update of the database of essential genes that includes both protein-coding genes and noncoding genomic elements","volume":"42","author":"Luo","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2021110815081235300_ref26","doi-asserted-by":"crossref","first-page":"6062","DOI":"10.1073\/pnas.0400782101","article-title":"A gene atlas of the mouse and human protein-encoding transcriptomes","volume":"101","author":"Su","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021110815081235300_ref27","doi-asserted-by":"crossref","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","article-title":"DrugBank 5.0: a major update to the DrugBank database for 2018","volume":"46","author":"Wishart","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2021110815081235300_ref28","doi-asserted-by":"crossref","first-page":"D457","DOI":"10.1093\/nar\/gkv1070","article-title":"KEGG as a reference resource for gene and protein annotation","volume":"44","author":"Kanehisa","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2021110815081235300_ref29","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nrg.2017.75","article-title":"Human gene essentiality","volume":"19","author":"Bartha","year":"2018","journal-title":"Nat Rev Genet"},{"key":"2021110815081235300_ref30","doi-asserted-by":"crossref","first-page":"R124","DOI":"10.1186\/gb-2010-11-12-r124","article-title":"Large scale comparison of global gene expression patterns in human and mouse","volume":"11","author":"Zheng-Bradley","year":"2010","journal-title":"Genome Biol"},{"key":"2021110815081235300_ref31","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 U S A"},{"key":"2021110815081235300_ref32","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1101\/gad.14.13.1595","article-title":"A conserved family of calcineurin regulators","volume":"14","author":"Kingsbury","year":"2000","journal-title":"Genes Dev"},{"key":"2021110815081235300_ref33","doi-asserted-by":"crossref","first-page":"3537","DOI":"10.1210\/en.2011-1814","article-title":"Mice lacking the calcineurin inhibitor Rcan2 have an isolated defect of osteoblast function","volume":"153","author":"Bassett","year":"2012","journal-title":"Endocrinology"},{"key":"2021110815081235300_ref34","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/his.13764","article-title":"Clinicopathological significance of RCAN2 production in gastric carcinoma","volume":"74","author":"Hattori","year":"2019","journal-title":"Histopathology"},{"key":"2021110815081235300_ref35","doi-asserted-by":"crossref","first-page":"38787","DOI":"10.1074\/jbc.M102829200","article-title":"Chronic overexpression of the calcineurin inhibitory gene DSCR1 (Adapt78) is associated with Alzheimer's disease","volume":"276","author":"Ermak","year":"2001","journal-title":"J Biol Chem"},{"key":"2021110815081235300_ref36","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0925-4773(00)00583-9","article-title":"Dscr1, a novel endogenous inhibitor of calcineurin signaling, is expressed in the primitive ventricle of the heart and during neurogenesis","volume":"101","author":"Casas","year":"2001","journal-title":"Mech Dev"},{"key":"2021110815081235300_ref37","doi-asserted-by":"crossref","first-page":"e253","DOI":"10.1038\/oncsis.2016.47","article-title":"KRAS mutation leads to decreased expression of regulator of calcineurin 2, resulting in tumor proliferation in colorectal cancer","volume":"5","author":"Niitsu","year":"2016","journal-title":"Oncogenesis"},{"key":"2021110815081235300_ref38","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.4049\/jimmunol.172.5.2731","article-title":"Of mice and not men: differences between mouse and human immunology","volume":"172","author":"Mestas","year":"2004","journal-title":"J Immunol"},{"key":"2021110815081235300_ref39","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1073\/pnas.1222738110","article-title":"Conservation and divergence in the transcriptional programs of the human and mouse immune systems","volume":"110","author":"Shay","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021110815081235300_ref40","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1089\/ars.2006.8.893","article-title":"Characterization of NO and cytokine production in immune-activated microglia and peritoneal macrophages derived from a mouse model expressing the human NOS2 gene on a mouse NOS2 knockout background","volume":"8","author":"Vitek","year":"2006","journal-title":"Antioxid Redox Signal"},{"key":"2021110815081235300_ref41","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.4049\/jimmunol.1301758","article-title":"Epigenetic silencing of the human NOS2 gene: rethinking the role of nitric oxide in human macrophage inflammatory responses","volume":"192","author":"Gross","year":"2014","journal-title":"J Immunol"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/22\/6\/bbab253\/41087926\/bbab253.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/22\/6\/bbab253\/41087926\/bbab253.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T06:52:51Z","timestamp":1672469571000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbab253\/6314723"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,5]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,11,5]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbab253","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,11]]},"published":{"date-parts":[[2021,7,5]]},"article-number":"bbab253"}}