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Yet the existing approaches in tackling this question are inadequate in accuracy and efficiency, demanding computational methods with higher identification power. Here, we proposed a new method called DGHNE to identify disease-causing genes through a heterogeneous biomedical network empowered by network enhancement. First, a disease\u2013disease association network was constructed by the cosine similarity scores between phenotype annotation vectors of diseases, and a new heterogeneous biomedical network was constructed by using disease\u2013gene associations to connect the disease\u2013disease network and gene\u2013gene network. Then, the heterogeneous biomedical network was further enhanced by using network embedding based on the Gaussian random projection. Finally, network propagation was used to identify candidate genes in the enhanced network. We applied DGHNE together with five other methods into the most updated disease\u2013gene association database termed DisGeNet. Compared with all other methods, DGHNE displayed the highest area under the receiver operating characteristic curve and the precision-recall curve, as well as the highest precision and recall, in both the global 5-fold cross-validation and predicting new disease\u2013gene associations. We further performed DGHNE in identifying the candidate causal genes of Parkinson\u2019s disease and diabetes mellitus, and the genes connecting hyperglycemia and diabetes mellitus. In all cases, the predicted causing genes were enriched in disease-associated gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways, and the gene\u2013disease associations were highly evidenced by independent experimental studies.<\/jats:p>","DOI":"10.1093\/bib\/bbac405","type":"journal-article","created":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T06:17:46Z","timestamp":1664000266000},"source":"Crossref","is-referenced-by-count":33,"title":["DGHNE: network enhancement-based method in identifying disease-causing genes through a heterogeneous biomedical network"],"prefix":"10.1093","volume":"23","author":[{"given":"Binsheng","family":"He","sequence":"first","affiliation":[{"name":"Academician Workstation, Changsha Medical University , Changsha 410219, China"},{"name":"Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University , Changsha 410219, P. R. China"},{"name":"School of pharmacy, Changsha Medical University , Changsha 410219, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3668-1472","authenticated-orcid":false,"given":"Kun","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Mathematical Sciences, Ocean University of China , Qingdao 266100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3045-5706","authenticated-orcid":false,"given":"Ju","family":"Xiang","sequence":"additional","affiliation":[{"name":"Academician Workstation, Changsha Medical University , Changsha 410219, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"Bing","sequence":"additional","affiliation":[{"name":"Academician Workstation, Changsha Medical University , Changsha 410219, China"},{"name":"Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University , Changsha 410219, P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jiangsu University , Zhenjiang 212001, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng","family":"Tian","sequence":"additional","affiliation":[{"name":"Geneis (Beijing) Co., Ltd. , Beijing 100102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity, Mailman School of Public Health, Columbia University , New York, NY, 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Xu","sequence":"additional","affiliation":[{"name":"Broad institute of MIT and Harvard, 415 Main Street , Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4689-8672","authenticated-orcid":false,"given":"Jialiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Academician Workstation, Changsha Medical University , Changsha 410219, China"},{"name":"Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University , Changsha 410219, P. 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