{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T16:20:43Z","timestamp":1732033243453},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,5,1]]},"abstract":"Abstract<\/jats:title>\n Motivation: Clinical diseases are characterized by distinct phenotypes. To identify disease genes is to elucidate the gene\u2013phenotype relationships. Mutations in functionally related genes may result in similar phenotypes. It is reasonable to predict disease-causing genes by integrating phenotypic data and genomic data. Some genetic diseases are genetically or phenotypically similar. They may share the common pathogenetic mechanisms. Identifying the relationship between diseases will facilitate better understanding of the pathogenetic mechanism of diseases.<\/jats:p>\n Results: In this article, we constructed a heterogeneous network by connecting the gene network and phenotype network using the phenotype\u2013gene relationship information from the OMIM database. We extended the random walk with restart algorithm to the heterogeneous network. The algorithm prioritizes the genes and phenotypes simultaneously. We use leave-one-out cross-validation to evaluate the ability of finding the gene\u2013phenotype relationship. Results showed improved performance than previous works. We also used the algorithm to disclose hidden disease associations that cannot be found by gene network or phenotype network alone. We identified 18 hidden disease associations, most of which were supported by literature evidence.<\/jats:p>\n Availability: The MATLAB code of the program is available at http:\/\/www3.ntu.edu.sg\/home\/aspatra\/research\/Yongjin_BI2010.zip<\/jats:p>\n Contact: \u00a0yongjin.li@gmail.com<\/jats:p>\n Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq108","type":"journal-article","created":{"date-parts":[[2010,3,10]],"date-time":"2010-03-10T02:34:03Z","timestamp":1268188443000},"page":"1219-1224","source":"Crossref","is-referenced-by-count":335,"title":["Genome-wide inferring gene\u2013phenotype relationship by walking on the heterogeneous network"],"prefix":"10.1093","volume":"26","author":[{"given":"Yongjin","family":"Li","sequence":"first","affiliation":[{"name":"School of Computer Engineering, Nanyang Technological University, Singapore"}]},{"given":"Jagdish C.","family":"Patra","sequence":"additional","affiliation":[{"name":"School of Computer Engineering, Nanyang Technological University, Singapore"}]}],"member":"286","published-online":{"date-parts":[[2010,3,9]]},"reference":[{"key":"2023012508160278200_B1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1093\/bioinformatics\/btk031","article-title":"SUSPECTS: enabling fast and effective prioritization of positional candidates","volume":"22","author":"Adie","year":"2006","journal-title":"Bioinformatics"},{"key":"2023012508160278200_B2","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nbt1203","article-title":"Gene prioritization through genomic data fusion","volume":"24","author":"Aerts","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"2023012508160278200_B3","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1126\/science.1076641","article-title":"Finding genes that underlie complex traits","volume":"298","author":"Anne","year":"2002","journal-title":"Science"},{"key":"2023012508160278200_B4","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/j.1399-0004.2005.00509.x","article-title":"Mapping phenotypes to language: a proposal to organize and standardize the clinical descriptions of malformations","volume":"68","author":"Biesecker","year":"2005","journal-title":"Clin. Genet."},{"issue":"Suppl.","key":"2023012508160278200_B5","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/ng1090","article-title":"Discovering genotypes underlying human phenotypes: past successes for Mendelian disease, future approaches for complex disease","volume":"33","author":"Botstein","year":"2003","journal-title":"Nat. Genet."},{"key":"2023012508160278200_B6","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1074\/jbc.M801645200","article-title":"Relative resistance of CDK5-phosphorylated CRMP2 to dephosphorylation","volume":"283","author":"Cole","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2023012508160278200_B7","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1371\/journal.pone.0008068","article-title":"Pathway analysis of GWAS provides new insights into genetic susceptibility to 3 inflammatory diseases","volume":"4","author":"Eleftherohorinou","year":"2009","journal-title":"PLoS One"},{"issue":"Suppl. 2","key":"2023012508160278200_B8","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":"2023012508160278200_B9","doi-asserted-by":"crossref","first-page":"R220","DOI":"10.1093\/hmg\/ddl197","article-title":"Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase signal transduction","volume":"15","author":"Gelb","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"2023012508160278200_B10","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1146\/annurev.genom.6.080604.162234","article-title":"Disease gene discovery through integrative genomics","volume":"6","author":"Giallourakis","year":"2005","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"2023012508160278200_B11","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"},{"issue":"Database Issue","key":"2023012508160278200_B12","doi-asserted-by":"crossref","first-page":"D514","DOI":"10.1093\/nar\/gki033","article-title":"Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders","volume":"33","author":"Hamosh","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2023012508160278200_B13","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1097\/MOL.0b013e32832d3a10","article-title":"Apolipoprotein E receptors in the nervous system","volume":"20","author":"Herz","year":"2009","journal-title":"Curr. Opin. Lipidol."},{"key":"2023012508160278200_B14","doi-asserted-by":"crossref","DOI":"10.1186\/1750-1172-3-22","article-title":"Gitelman syndrome","volume":"3","author":"Knoers","year":"2008","journal-title":"Orphanet J. Rare Dis."},{"key":"2023012508160278200_B15","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.ajhg.2008.02.013","article-title":"Walking the interactome for prioritization of candidate disease genes","volume":"82","author":"K\u00f6hler","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"2023012508160278200_B16","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nbt1295","article-title":"A human phenome-interactome network of protein complexes implicated in genetic disorders","volume":"25","author":"Lage","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"2023012508160278200_B17","doi-asserted-by":"crossref","first-page":"9880","DOI":"10.1073\/pnas.0802208105","article-title":"The implications of human metabolic network topology for disease comorbidity","volume":"105","author":"Lee","year":"2008","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012508160278200_B18","doi-asserted-by":"crossref","first-page":"R91","DOI":"10.1186\/gb-2009-10-9-r91","article-title":"Genome-wide prioritization of disease genes and identification of disease-disease associations from an integrated human functional linkage network","volume":"10","author":"Linghu","year":"2009","journal-title":"Genome Biol."},{"key":"2023012508160278200_B19","doi-asserted-by":"crossref","first-page":"e4346","DOI":"10.1371\/journal.pone.0004346","article-title":"A pathway-based view of human diseases and disease relationships","volume":"4","author":"Li","year":"2009","journal-title":"PLoS ONE"},{"issue":"Suppl. 1","key":"2023012508160278200_B20","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1186\/1471-2105-11-S1-S20","article-title":"Integration of multiple data sources to prioritize candidate genes using discounted rating system","volume":"11","author":"Li","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2023012508160278200_B21","doi-asserted-by":"crossref","first-page":"3108","DOI":"10.1093\/nar\/gkh605","article-title":"Genome-wide identification of genes likely to be involved in human genetic disease","volume":"32","author":"L\u00f3pez-Bigas","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2023012508160278200_B22","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1353\/pbm.1969.0039","article-title":"On lumpers and splitters, or the nosology of genetic disease","volume":"12","author":"McKusick","year":"1969","journal-title":"Perspect. Biol. Med."},{"key":"2023012508160278200_B23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1399-0004.2006.00708.x","article-title":"The modular nature of genetic diseases","volume":"71","author":"Oti","year":"2007","journal-title":"Clin. Genet."},{"key":"2023012508160278200_B24","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.tig.2007.12.005","article-title":"Phenome connections","volume":"24","author":"Oti","year":"2008","journal-title":"Trends Genet."},{"key":"2023012508160278200_B25","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.ajhg.2009.10.026","article-title":"The biological coherence of human phenome databases","volume":"85","author":"Oti","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"2023012508160278200_B26","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":"2023012508160278200_B27","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1101\/gr.1680803","article-title":"Development of human protein reference database as an initial platform for approaching systems biology in humans","volume":"13","author":"Peri","year":"2003","journal-title":"Genome Res."},{"key":"2023012508160278200_B28","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1371\/journal.pgen.1000534","article-title":"Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions","volume":"5","author":"Raychaudhuri","year":"2009","journal-title":"PLoS Genet."},{"key":"2023012508160278200_B29","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.ajhg.2008.09.017","article-title":"The Human Phenotype Ontology: a tool for annotating and analyzing human hereditary disease","volume":"83","author":"Robinson","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"2023012508160278200_B30","doi-asserted-by":"crossref","first-page":"11694","DOI":"10.1073\/pnas.0704820104","article-title":"Probing genetic overlap among complex human phenotypes","volume":"104","author":"Rzhetsky","year":"2007","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012508160278200_B31","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2164-10-22","article-title":"BioMart\u2013biological queries made easy","volume":"10","author":"Smedley","year":"2009","journal-title":"BMC Genomics"},{"key":"2023012508160278200_B32","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00018-007-7270-0","article-title":"Prolyl isomerase, Pin1: new findings of post-translational modifications and physiological substrates in cancer, asthma and Alzheimer's disease","volume":"65","author":"Takahashi","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"2023012508160278200_B33","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1080\/13816810601013146","article-title":"Lumpers or splitters? the role of molecular diagnosis in Leber congenital amaurosis","volume":"27","author":"Traboulsi","year":"2006","journal-title":"Ophthalmic Genet."},{"key":"2023012508160278200_B34","doi-asserted-by":"crossref","first-page":"R75","DOI":"10.1186\/gb-2003-4-11-r75","article-title":"POCUS: mining genomic sequence annotation to predict disease genes","volume":"4","author":"Turner","year":"2003","journal-title":"Genome Biol."},{"key":"2023012508160278200_B35","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/sj.ejhg.5201585","article-title":"A text-mining analysis of the human phenome","volume":"14","author":"van Driel","year":"2006","journal-title":"Eur. J. Hum. Genet."},{"key":"2023012508160278200_B36","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1086\/522374","article-title":"Pathway-based approaches for analysis of genomewide association studies","volume":"81","author":"Wang","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"2023012508160278200_B37","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1086\/423393","article-title":"Evidence for a novel late-onset alzheimer disease locus on chromosome 19p13.2","volume":"75","author":"Wijsman","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"2023012508160278200_B38","doi-asserted-by":"crossref","DOI":"10.1038\/msb.2008.27","article-title":"Network-based global inference of human disease genes","volume":"4","author":"Wu","year":"2008","journal-title":"Mol. Syst. Biol."},{"key":"2023012508160278200_B39","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1093\/bioinformatics\/btl467","article-title":"Discovering disease-genes by topological features in human protein-protein interaction network","volume":"22","author":"Xu","year":"2006","journal-title":"Bioinformatics"},{"key":"2023012508160278200_B40","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.neuroscience.2006.11.052","article-title":"DNA damage responses in neural cells: Focus on the telomere","volume":"145","author":"Zhang","year":"2007","journal-title":"Neuroscience"},{"key":"2023012508160278200_B41","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1109\/ICDM.2007.57","article-title":"Co-ranking authors and documents in a heterogeneous network","volume-title":"IEEE International Conference on Data Mining (ICDM 2007)","author":"Zhou","year":"2007"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/26\/9\/1219\/48855372\/bioinformatics_26_9_1219.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/26\/9\/1219\/48855372\/bioinformatics_26_9_1219.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T08:16:40Z","timestamp":1674634600000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/26\/9\/1219\/199640"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,9]]},"references-count":41,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2010,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btq108","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,5,1]]},"published":{"date-parts":[[2010,3,9]]}}}