{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T04:46:09Z","timestamp":1777178769861,"version":"3.51.4"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":3015,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Understanding the role of genetics in diseases is one of the most important aims of the biological sciences. The completion of the Human Genome Project has led to a rapid increase in the number of publications in this area. However, the coverage of curated databases that provide information manually extracted from the literature is limited. Another challenge is that determining disease-related genes requires laborious experiments. Therefore, predicting good candidate genes before experimental analysis will save time and effort. We introduce an automatic approach based on text mining and network analysis to predict gene-disease associations. We collected an initial set of known disease-related genes and built an interaction network by automatic literature mining based on dependency parsing and support vector machines. Our hypothesis is that the central genes in this disease-specific network are likely to be related to the disease. We used the degree, eigenvector, betweenness and closeness centrality metrics to rank the genes in the network.<\/jats:p>\n               <jats:p>Results: The proposed approach can be used to extract known and to infer unknown gene-disease associations. We evaluated the approach for prostate cancer. Eigenvector and degree centrality achieved high accuracy. A total of 95% of the top 20 genes ranked by these methods are confirmed to be related to prostate cancer. On the other hand, betweenness and closeness centrality predicted more genes whose relation to the disease is currently unknown and are candidates for experimental study.<\/jats:p>\n               <jats:p>Availability: A web-based system for browsing the disease-specific gene-interaction networks is available at: http:\/\/gin.ncibi.org<\/jats:p>\n               <jats:p>Contact: \u00a0radev@umich.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/btn182","type":"journal-article","created":{"date-parts":[[2008,6,27]],"date-time":"2008-06-27T07:43:13Z","timestamp":1214552593000},"page":"i277-i285","source":"Crossref","is-referenced-by-count":290,"title":["Identifying gene-disease associations using centrality on a literature mined gene-interaction network"],"prefix":"10.1093","volume":"24","author":[{"given":"Arzucan","family":"\u00d6zg\u00fcr","sequence":"first","affiliation":[{"name":"1 Electrical Engineering and Computer Science and 2School of Information, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thuy","family":"Vu","sequence":"additional","affiliation":[{"name":"1 Electrical Engineering and Computer Science and 2School of Information, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fcne\u015f","family":"Erkan","sequence":"additional","affiliation":[{"name":"1 Electrical Engineering and Computer Science and 2School of Information, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dragomir R.","family":"Radev","sequence":"additional","affiliation":[{"name":"1 Electrical Engineering and Computer Science and 2School of Information, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"1 Electrical Engineering and Computer Science and 2School of Information, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,7,1]]},"reference":[{"key":"2023020210395598800_B1","first-page":"109","article-title":"A literature based method for identifying gene-disease connections","author":"Adamic","year":"2002"},{"key":"2023020210395598800_B2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3844\/ajbbsp.2004.145.152","article-title":"A new text mining approach for finding protein-to-disease associations","volume":"1","author":"Al-Mubaid","year":"2005","journal-title":"Am J Biochem Biotechnol"},{"key":"2023020210395598800_B3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The gene ontology consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet"},{"key":"2023020210395598800_B4","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1093\/nar\/gkg056","article-title":"Bind \u2013 the biomolecular interaction network database","volume":"31","author":"Bader","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"2023020210395598800_B5","article-title":"Cbioc: web-based collaborative curation of molecular interaction data from biomedical literature","volume-title":"The Genetics Society of America 1st International Biocurator Meeting","author":"Baral","year":"2005"},{"key":"2023020210395598800_B6","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1093\/bioinformatics\/bti273","article-title":"Online predicted human interaction database ophid","volume":"21","author":"Brown","year":"2005","journal-title":"Bioinformatics"},{"key":"2023020210395598800_B7","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/1471-2105-5-147","article-title":"Content-rich biological network constructed by mining pubmed abstracts","volume":"5","author":"Chen","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"2023020210395598800_B8","first-page":"367","article-title":"Mining Alzheimer disease relevant proteins from integrated protein interactome data","volume":"11","author":"Chen","year":"2006","journal-title":"Pac. Symp. Biocomput"},{"key":"2023020210395598800_B9","first-page":"1035","article-title":"Rational kernels: theory and algorithms","volume":"5","author":"Cortes","year":"2004","journal-title":"J. Mach. Learn. Res"},{"key":"2023020210395598800_B10","article-title":"Generating typed dependency parses from phrase Structure Parses","author":"de Marneffe","year":"2006"},{"key":"2023020210395598800_B11","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1613\/jair.1523","article-title":"Lexrank: graph-based lexical centrality as salience in text summarization","volume":"22","author":"Erkan","year":"2004","journal-title":"J. Artif. Intell. Res. (JAIR)"},{"key":"2023020210395598800_B12","first-page":"228","article-title":"Semi-supervised classification for extracting protein interaction sentences using dependency parsing","author":"Erkan","year":"2007"},{"key":"2023020210395598800_B13","first-page":"658","article-title":"MavenRank: identifying influential members of the US senate using lexical centrality","author":"Fader","year":"2007"},{"key":"2023020210395598800_B14","volume-title":"Statistical Methods for Research Workers","author":"Fisher","year":"1970","edition":"14th edn"},{"key":"2023020210395598800_B15","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2307\/3033543","article-title":"A set of measures of centrality based on betweenness","volume":"40","author":"Freeman","year":"1977","journal-title":"Sociometry"},{"key":"2023020210395598800_B16","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0378-8733(78)90021-7","article-title":"Centrality in social networks: conceptual clarification","volume":"1","author":"Freeman","year":"1979","journal-title":"Soc. Networks"},{"key":"2023020210395598800_B17","doi-asserted-by":"crossref","first-page":"S110","DOI":"10.1093\/bioinformatics\/18.suppl_2.S110","article-title":"A similarity-based method for genome-wide prediction of disease-relevant human genes","volume":"18","author":"Freudenberg","year":"2002","journal-title":"Bioinformatics"},{"key":"2023020210395598800_B18","doi-asserted-by":"crossref","first-page":"8685","DOI":"10.1073\/pnas.0701361104","article-title":"The human disease network","volume":"104","author":"Goh","year":"2007","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020210395598800_B19","first-page":"28","article-title":"Mining gene-disease relationships from biomedical literature: weighting protein-protein interactions and connectivity measures","volume":"12","author":"Gonzalez","year":"2007","journal-title":"Pac. Symp. iocomput"},{"key":"2023020210395598800_B20","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1093\/molbev\/msi072","article-title":"Comparative genomics of centrality and essentiality in three eukaryotic protein-interaction networks","volume":"22","author":"Hahn","year":"2005","journal-title":"Mol. Biol. Evol"},{"key":"2023020210395598800_B21","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.bbalip.2007.04.010","article-title":"Lysophosphatidic acid induces prostate cancer pc3 cell migration via activation of lpa(1), p42 and p38alpha","volume":"1771","author":"Hao","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"2023020210395598800_B22","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/sj.bjc.6600747","article-title":"Polymorphism of the insulin gene is associated with increased prostate cancer risk","volume":"88","author":"Ho","year":"2003","journal-title":"Br. J. Cancer"},{"key":"2023020210395598800_B23","doi-asserted-by":"crossref","first-page":"ii252","DOI":"10.1093\/bioinformatics\/bti1142","article-title":"Implementing the ihop concept for navigation of biomedical literature","volume":"21","author":"Hoffmann","year":"2005","journal-title":"Bioinformatics"},{"key":"2023020210395598800_B24","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/35057062","article-title":"Initial sequencing and analysis of the human genome","volume":"409","author":"International Human Genome Sequencing Consortium","year":"2001","journal-title":"Nature"},{"key":"2023020210395598800_B25","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/35075138","article-title":"Lethality and centrality in protein networks","volume":"411","author":"Jeong","year":"2001","journal-title":"Nature"},{"key":"2023020210395598800_B26","article-title":"Making Large-Scale SVM Learning Practical","volume-title":"Advances in Kernel Methods-Support Vector Learning","author":"Joachims","year":"1999"},{"key":"2023020210395598800_B27","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1155\/JBB.2005.96","article-title":"High-betweenness proteins in the yeast protein interaction network","volume":"2","author":"Joy","year":"2005","journal-title":"J. Biomed. Biotechnol"},{"key":"2023020210395598800_B28","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2008-9-s2-s6","article-title":"Introducing meta-services for biomedical information extraction","author":"Leitner","year":"2008","journal-title":"Genome Biol"},{"key":"2023020210395598800_B29","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/nar\/gkg008","article-title":"Pgdb: a curated and integrated database of genes related to the prostate","volume":"31","author":"Li","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"2023020210395598800_B30","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1137\/S003614450342480","article-title":"The structure and function of complex networks","volume":"45","author":"Newman","year":"2003","journal-title":"SIAM Rev"},{"key":"2023020210395598800_B31","unstructured":"OMIM\n          Online Mendelian inheritance in man, OMIM (TM). McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD)\n          2007\n          Available at http:\/\/www.ncbi.nlm.nih.gov\/omim\/last accessed November 19, 2007"},{"key":"2023020210395598800_B32","article-title":"The pagerank citation ranking: bringing order to the web","volume-title":"Technical report, Stanford Digital Library Technologies Project","author":"Page","year":"1998"},{"key":"2023020210395598800_B33","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/ng895","article-title":"Association of genes to genetically inherited diseases using data mining","volume":"31","author":"Perez-Iratxeta","year":"2002","journal-title":"Nat. Genet"},{"key":"2023020210395598800_B34","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/1471-2156-6-45","article-title":"G2d: a tool for mining genes associated with disease","volume":"6","author":"Perez-Iratxeta","year":"2005","journal-title":"BMC Genet"},{"key":"2023020210395598800_B35","first-page":"16","article-title":"A maximum entropy approach to identifying sentence boundaries","author":"Reynar","year":"1997"},{"key":"2023020210395598800_B36","doi-asserted-by":"crossref","first-page":"39480","DOI":"10.1074\/jbc.M603495200","article-title":"Cannabinoid receptor agonist-induced apoptosis of human prostate cancer cells lncap proceeds through sustained activation of erk1\/2 leading to g1 cell cycle arrest","volume":"281","author":"Sarfaraz","year":"2006","journal-title":"J. Biol. Chem"},{"key":"2023020210395598800_B37","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1038\/82360","article-title":"A network of protein-protein interactions in yeast","volume":"18","author":"Schwikowski","year":"2000","journal-title":"Nat. Biotechnol"},{"key":"2023020210395598800_B38","doi-asserted-by":"crossref","first-page":"12123","DOI":"10.1073\/pnas.2032324100","article-title":"Protein complexes and functional modules in molecular networks","volume":"100","author":"Spirin","year":"2003","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020210395598800_B39","first-page":"382","article-title":"Developing a robust part-of-speech tagger for biomedical text","author":"Tsuruoka","year":"2005"},{"key":"2023020210395598800_B40","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/sj.ejhg.5200918","article-title":"A new web-based data mining tool for the identification of candidate genes for human genetic disorders","volume":"11","author":"van Driel","year":"2002","journal-title":"Eur. J. Hum. Genet"},{"key":"2023020210395598800_B41","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1126\/science.1058040","article-title":"The sequence of the human genome","volume":"291","author":"Venter","year":"2001","journal-title":"Science"},{"issue":"(D255-7)","key":"2023020210395598800_B42","first-page":"1257","article-title":"Genew: the human gene nomenclature database, 2004 updates","volume":"32","author":"Wain","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"2023020210395598800_B43","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/pros.10187","article-title":"Experimental therapy of human prostate cancer by inhibiting mdm2 expression with novel mixed-backbone antisense oligonucleotides: in vitro and in vivo activities and mechanisms","volume":"54","author":"Wang","year":"2003","journal-title":"Prostate"},{"key":"2023020210395598800_B44","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/30918","article-title":"Collective dynamics of small-world networks","volume":"393","author":"Watts","year":"1998","journal-title":"Nature"},{"key":"2023020210395598800_B45","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/sj.pcan.4500933","article-title":"Global analysis of differentially expressed genes in androgen-independent prostate cancer","volume":"10","author":"Wei","year":"2007","journal-title":"Prostate Cancer Prostatic Dis"},{"key":"2023020210395598800_B46","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/ng1242","article-title":"Evolutionary conservation of motif constituents in the yeast protein interaction network","volume":"35","author":"Wuchty","year":"2003","journal-title":"Nat. Genet"},{"key":"2023020210395598800_B47","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0014-5793(01)03293-8","article-title":"Mint: a molecular interaction database","volume":"513","author":"Zanzoni","journal-title":"FEBS Lett"},{"key":"2023020210395598800_B48","doi-asserted-by":"crossref","first-page":"11636","DOI":"10.1073\/pnas.1934692100","article-title":"Antisense therapy targeting mdm2 oncogene in prostate cancer: effects on proliferation, apoptosis, multiple gene expression, and chemotherapy","volume":"100","author":"Zhang","year":"2003","journal-title":"Proc. Natl Acad. Sci"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/13\/i277\/49052827\/bioinformatics_24_13_i277.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/13\/i277\/49052827\/bioinformatics_24_13_i277.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T12:23:35Z","timestamp":1675340615000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/24\/13\/i277\/236041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7,1]]},"references-count":48,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2008,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btn182","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2008,7,1]]},"published":{"date-parts":[[2008,7,1]]}}}