{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T23:32:43Z","timestamp":1772148763982,"version":"3.50.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1046,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: MicroRNAs (miRNAs) are a highly abundant class of non-coding RNA genes involved in cellular regulation and thus also diseases. Despite miRNAs being important disease factors, miRNA\u2013disease associations remain low in number and of variable reliability. Furthermore, existing databases and prediction methods do not explicitly facilitate forming hypotheses about the possible molecular causes of the association, thereby making the path to experimental follow-up longer.<\/jats:p>\n               <jats:p>Results: Here we present miRPD in which miRNA\u2013Protein\u2013Disease associations are explicitly inferred. Besides linking miRNAs to diseases, it directly suggests the underlying proteins involved, which can be used to form hypotheses that can be experimentally tested. The inference of miRNAs and diseases is made by coupling known and predicted miRNA\u2013protein associations with protein\u2013disease associations text mined from the literature. We present scoring schemes that allow us to rank miRNA\u2013disease associations inferred from both curated and predicted miRNA targets by reliability and thereby to create high- and medium-confidence sets of associations. Analyzing these, we find statistically significant enrichment for proteins involved in pathways related to cancer and type I diabetes mellitus, suggesting either a literature bias or a genuine biological trend. We show by example how the associations can be used to extract proteins for disease hypothesis.<\/jats:p>\n               <jats:p>Availability and implementation: All datasets, software and a searchable Web site are available at http:\/\/mirpd.jensenlab.org.<\/jats:p>\n               <jats:p>Contact: \u00a0lars.juhl.jensen@cpr.ku.dk or gorodkin@rth.dk<\/jats:p>","DOI":"10.1093\/bioinformatics\/btt677","type":"journal-article","created":{"date-parts":[[2013,11,23]],"date-time":"2013-11-23T03:29:55Z","timestamp":1385177395000},"page":"392-397","source":"Crossref","is-referenced-by-count":181,"title":["Protein-driven inference of miRNA\u2013disease associations"],"prefix":"10.1093","volume":"30","author":[{"given":"S\u00f8ren","family":"M\u00f8rk","sequence":"first","affiliation":[{"name":"1 Center for non-coding RNA in Technology and Health, 2Department of Veterinary Clinical and Animal Sciences, 3Department of Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research and 4The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark"},{"name":"1 Center for non-coding RNA in Technology and Health, 2Department of Veterinary Clinical and Animal Sciences, 3Department of Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research and 4The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark"}]},{"given":"Sune","family":"Pletscher-Frankild","sequence":"additional","affiliation":[{"name":"1 Center for non-coding RNA in Technology and Health, 2Department of Veterinary Clinical and Animal Sciences, 3Department of Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research and 4The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark"}]},{"given":"Albert","family":"Palleja Caro","sequence":"additional","affiliation":[{"name":"1 Center for non-coding RNA in Technology and Health, 2Department of Veterinary Clinical and Animal Sciences, 3Department of Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research and 4The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark"},{"name":"1 Center for non-coding RNA in Technology and Health, 2Department of Veterinary Clinical and Animal Sciences, 3Department of Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research and 4The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark"}]},{"given":"Jan","family":"Gorodkin","sequence":"additional","affiliation":[{"name":"1 Center for non-coding RNA in Technology and Health, 2Department of Veterinary Clinical and Animal Sciences, 3Department of Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research and 4The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark"},{"name":"1 Center for non-coding RNA in Technology and Health, 2Department of Veterinary Clinical and Animal Sciences, 3Department of Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research and 4The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark"}]},{"given":"Lars Juhl","family":"Jensen","sequence":"additional","affiliation":[{"name":"1 Center for non-coding RNA in Technology and Health, 2Department of Veterinary Clinical and Animal Sciences, 3Department of Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research and 4The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark"}]}],"member":"286","published-online":{"date-parts":[[2013,11,21]]},"reference":[{"key":"2023012710411924200_btt677-B1","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nature02871","article-title":"The functions of animal microRNAs","volume":"431","author":"Ambros","year":"2004","journal-title":"Nature"},{"key":"2023012710411924200_btt677-B2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"2023012710411924200_btt677-B3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: target recognition and regulatory functions","volume":"136","author":"Bartel","year":"2009","journal-title":"Cell"},{"key":"2023012710411924200_btt677-B4","doi-asserted-by":"crossref","first-page":"R90","DOI":"10.1186\/gb-2010-11-8-r90","article-title":"Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites","volume":"11","author":"Betel","year":"2010","journal-title":"Genome Biol."},{"key":"2023012710411924200_btt677-B5","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1755-8794-6-12","article-title":"Similarity-based methods for potential human microRNA-disease association prediction","volume":"6","author":"Chen","year":"2013","journal-title":"BMC Med. Genomics"},{"key":"2023012710411924200_btt677-B6","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1039\/c2mb25180a","article-title":"Rwrmda: predicting novel human microRNA disease associations","volume":"8","author":"Chen","year":"2012","journal-title":"Mol. Biosyst."},{"key":"2023012710411924200_btt677-B7","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/1752-0509-6-90","article-title":"Multiple independent analyses reveal transcription factors are an enriched functional class associated with microRNAs","volume":"6","author":"Croft","year":"2012","journal-title":"BMC Syst. Biol."},{"key":"2023012710411924200_btt677-B8","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.jbi.2011.05.002","article-title":"mirwalk - database: prediction of possible miRNA binding sites by \u201cwalking\u201d the genes of 3 genomes","volume":"44","author":"Dweep","year":"2011","journal-title":"J. Biomed. Inform."},{"key":"2023012710411924200_btt677-B9","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/nrg3074","article-title":"Non-coding RNAs in human disease","volume":"12","author":"Esteller","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"2023012710411924200_btt677-B10","doi-asserted-by":"crossref","first-page":"e6121","DOI":"10.1371\/journal.pone.0006121","article-title":"Evidence for X-chromosomal schizophrenia associated with microRNA alterations","volume":"4","author":"Feng","year":"2009","journal-title":"PLoS One"},{"key":"2023012710411924200_btt677-B11","doi-asserted-by":"crossref","first-page":"D808","DOI":"10.1093\/nar\/gks1094","article-title":"String v9.1: protein-protein interaction networks, with increased coverage and integration","volume":"41","author":"Franceschini","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2023012710411924200_btt677-B12","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1101\/gr.082701.108","article-title":"Most mammalian mRNAs are conserved targets of microRNAs","volume":"19","author":"Friedman","year":"2009","journal-title":"Genome Res."},{"key":"2023012710411924200_btt677-B13","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1038\/nsmb.2115","article-title":"Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs","volume":"18","author":"Garcia","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2023012710411924200_btt677-B14","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.molcel.2007.06.017","article-title":"MicroRNA targeting specificity in mammals: determinants beyond seed pairing","volume":"27","author":"Grimson","year":"2007","journal-title":"Mol. Cell"},{"key":"2023012710411924200_btt677-B15","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/nature03552","article-title":"A microRNA polycistron as a potential human oncogene","volume":"435","author":"He","year":"2005","journal-title":"Nature"},{"key":"2023012710411924200_btt677-B16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023012710411924200_btt677-B17","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using David bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"2023012710411924200_btt677-B18","doi-asserted-by":"crossref","first-page":"D98","DOI":"10.1093\/nar\/gkn714","article-title":"miR2Disease: a manually curated database for microRNA deregulation in human disease","volume":"37","author":"Jiang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023012710411924200_btt677-B19","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/1752-0509-4-S1-S2","article-title":"Prioritization of disease microRNAs through a human phenome-microRNAome network","volume":"4","author":"Jiang","year":"2010","journal-title":"BMC Syst. Biol."},{"key":"2023012710411924200_btt677-B20","doi-asserted-by":"crossref","first-page":"D109","DOI":"10.1093\/nar\/gkr988","article-title":"KEGG for integration and interpretation of large-scale molecular datasets","volume":"40","author":"Kanehisa","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2023012710411924200_btt677-B21","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":"2023012710411924200_btt677-B22","doi-asserted-by":"crossref","first-page":"D152","DOI":"10.1093\/nar\/gkq1027","article-title":"mirbase: integrating microRNA annotation and deep-sequencing data","volume":"39","author":"Kozomara","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2023012710411924200_btt677-B23","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/ng1536","article-title":"Combinatorial microRNA target predictions","volume":"37","author":"Krek","year":"2005","journal-title":"Nat. Genet."},{"key":"2023012710411924200_btt677-B24","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ymeth.2007.09.005","article-title":"Experimental validation of miRNA targets","volume":"44","author":"Kuhn","year":"2008","journal-title":"Methods"},{"key":"2023012710411924200_btt677-B25","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/0092-8674(93)90529-Y","article-title":"The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14","volume":"75","author":"Lee","year":"1993","journal-title":"Cell"},{"key":"2023012710411924200_btt677-B26","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1039\/C0MB00230E","article-title":"Alteration of microRNA expression correlates to fatty acid-mediated insulin resistance in mouse myoblasts","volume":"7","author":"Li","year":"2011","journal-title":"Mol. Biosyst."},{"key":"2023012710411924200_btt677-B27","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nrendo.2009.101","article-title":"Sirt1 and insulin resistance","volume":"5","author":"Liang","year":"2009","journal-title":"Nat. Rev. Endocrinol."},{"key":"2023012710411924200_btt677-B28","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nature03315","article-title":"Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs","volume":"433","author":"Lim","year":"2005","journal-title":"Nature"},{"key":"2023012710411924200_btt677-B29","doi-asserted-by":"crossref","first-page":"e3420","DOI":"10.1371\/journal.pone.0003420","article-title":"An analysis of human microRNA and disease associations","volume":"3","author":"Lu","year":"2008","journal-title":"PLoS One"},{"key":"2023012710411924200_btt677-B30","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nature02873","article-title":"Mechanisms of gene silencing by double-stranded RNA","volume":"431","author":"Meister","year":"2004","journal-title":"Nature"},{"key":"2023012710411924200_btt677-B31","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1016\/j.cell.2012.02.005","article-title":"MicroRNAs in stress signaling and human disease","volume":"148","author":"Mendell","year":"2012","journal-title":"Cell"},{"key":"2023012710411924200_btt677-B32","doi-asserted-by":"crossref","first-page":"e65390","DOI":"10.1371\/journal.pone.0065390","article-title":"The species and organisms resources for fast and accurate identification of taxonomic names in text","volume":"8","author":"Pafilis","year":"2013","journal-title":"PLoS One"},{"key":"2023012710411924200_btt677-B33","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nature03076","article-title":"A pancreatic islet-specific microRNA regulates insulin secretion","volume":"432","author":"Poy","year":"2004","journal-title":"Nature"},{"key":"2023012710411924200_btt677-B34","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ygeno.2010.10.004","article-title":"Omir: identification of associations between omim diseases and microRNAs","volume":"97","author":"Rossi","year":"2011","journal-title":"Genomics"},{"key":"2023012710411924200_btt677-B35","doi-asserted-by":"crossref","first-page":"R6","DOI":"10.1186\/gb-2010-11-1-r6","article-title":"PhenomiR: a knowledgebase for microRNA expression in diseases and biological processes","volume":"11","author":"Ruepp","year":"2010","journal-title":"Genome Biol."},{"key":"2023012710411924200_btt677-B36","doi-asserted-by":"crossref","first-page":"D940","DOI":"10.1093\/nar\/gkr972","article-title":"Disease ontology: a backbone for disease semantic integration","volume":"40","author":"Schriml","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2023012710411924200_btt677-B37","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nature09783","article-title":"Pervasive roles of microRNAs in cardiovascular biology","volume":"469","author":"Small","year":"2011","journal-title":"Nature"},{"key":"2023012710411924200_btt677-B38","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1002\/gcc.20902","article-title":"Identification of miR-374a as a prognostic marker for survival in patients with early-stage nonsmall cell lung cancer","volume":"50","author":"V\u00f5sa","year":"2011","journal-title":"Genes Chromosomes Cancer"},{"key":"2023012710411924200_btt677-B39","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/0092-8674(93)90530-4","article-title":"Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in c","volume":"75","author":"Wightman","year":"1993","journal-title":"elegans. Cell"},{"key":"2023012710411924200_btt677-B40","doi-asserted-by":"crossref","first-page":"7653","DOI":"10.1093\/nar\/gks538","article-title":"Prioritizing cancer-related key miRNA-target interactions by integrative genomics","volume":"40","author":"Xiao","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2023012710411924200_btt677-B41","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s11010-011-1136-3","article-title":"Microrna- 1 represses cx43 expression in viral myocarditis","volume":"362","author":"Xu","year":"2012","journal-title":"Mol. Cell Biochem."},{"key":"2023012710411924200_btt677-B42","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1039\/C2MB25360G","article-title":"Dissection of the potential characteristic of miRNA-miRNA functional synergistic regulations","volume":"9","author":"Xu","year":"2013","journal-title":"Mol. Biosyst."},{"key":"2023012710411924200_btt677-B43","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1186\/1471-2164-11-S4-S5","article-title":"dbDEMC: a database of differentially expressed miRNAs in human cancers","volume":"11","author":"Yang","year":"2010","journal-title":"BMC Genomics"},{"key":"2023012710411924200_btt677-B44","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1007\/s00125-012-2539-8","article-title":"Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity","volume":"55","author":"Zhou","year":"2012","journal-title":"Diabetologia"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/30\/3\/392\/48915061\/bioinformatics_30_3_392.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/30\/3\/392\/48915061\/bioinformatics_30_3_392.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T10:55:46Z","timestamp":1674816946000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/30\/3\/392\/227866"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,21]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btt677","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2014,2,1]]},"published":{"date-parts":[[2013,11,21]]}}}