title: DNetDB: The human disease network database based on dysfunctional regulation mechanism.
abstract: Disease similarity study provides new insights into disease taxonomy, pathogenesis, which plays a guiding role in diagnosis and treatment. The early studies were limited to estimate disease similarities based on clinical manifestations, disease-related genes, medical vocabulary concepts or registry data, which were inevitably biased to well-studied diseases and offered small chance of discovering novel findings in disease relationships. In other words, genome-scale expression data give us another angle to address this problem since simultaneous measurement of the expression of thousands of genes allows for the exploration of gene transcriptional regulation, which is believed to be crucial to biological functions. Although differential expression analysis based methods have the potential to explore new disease relationships, it is difficult to unravel the upstream dysregulation mechanisms of diseases. We therefore estimated disease similarities based on gene expression data by using differential coexpression analysis, a recently emerging method, which has been proved to be more potential to capture dysfunctional regulation mechanisms than differential expression analysis. A total of 1,326 disease relationships among 108 diseases were identified, and the relevant information constituted the human disease network database (DNetDB). Benefiting from the use of differential coexpression analysis, the potential common dysfunctional regulation mechanisms shared by disease pairs (i.e. disease relationships) were extracted and presented. Statistical indicators, common disease-related genes and drugs shared by disease pairs were also included in DNetDB. In total, 1,326 disease relationships among 108 diseases, 5,598 pathways, 7,357 disease-related genes and 342 disease drugs are recorded in DNetDB, among which 3,762 genes and 148 drugs are shared by at least two diseases. DNetDB is the first database focusing on disease similarity from the viewpoint of gene regulation mechanism. It provides an easy-to-use web interface to search and browse the disease relationships and thus helps to systematically investigate etiology and pathogenesis, perform drug repositioning, and design novel therapeutic interventions.Database URL: http://app.scbit.org/DNetDB/ #.
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai, 200235, P.R. China.|Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai, 200235, P.R. China.
authors.forename: Su-Juan
authors.initials: SJ
authors.lastname: Wu
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai, 200235, P.R. China.|Shanghai Industrial Technology Institute, 1278 Keyuan Road, Shanghai, 201203, P.R. China.
authors.forename: Shao-You
authors.initials: SY
authors.lastname: Yang
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai, 200235, P.R. China.|Shanghai Industrial Technology Institute, 1278 Keyuan Road, Shanghai, 201203, P.R. China.
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Peng
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai, 200235, P.R. China.|Shanghai Industrial Technology Institute, 1278 Keyuan Road, Shanghai, 201203, P.R. China.
authors.forename: Shi-Nuo
authors.initials: SN
authors.lastname: Wang
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai, 200235, P.R. China.|Shanghai Industrial Technology Institute, 1278 Keyuan Road, Shanghai, 201203, P.R. China.
authors.forename: Fu-Yan
authors.initials: FY
authors.lastname: Wang
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai, 200235, P.R. China.|Shanghai Industrial Technology Institute, 1278 Keyuan Road, Shanghai, 201203, P.R. China.
authors.forename: Yu-Xing
authors.initials: YX
authors.lastname: Song
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai, 200235, P.R. China.|Shanghai Industrial Technology Institute, 1278 Keyuan Road, Shanghai, 201203, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Qi
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai, 200235, P.R. China. yxli@scbit.org.|Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, P.R. China. yxli@scbit.org.|Shanghai Industrial Technology Institute, 1278 Keyuan Road, Shanghai, 201203, P.R. China. yxli@scbit.org.|Shanghai Engineering Research Center of Pharmaceutical Translation, 1278 Keyuan Road, Shanghai, 201203, P.R. China. yxli@scbit.org.
authors.forename: Yi-Xue
authors.initials: YX
authors.lastname: Li
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai, 200235, P.R. China. yyli@scbit.org.|Shanghai Industrial Technology Institute, 1278 Keyuan Road, Shanghai, 201203, P.R. China. yyli@scbit.org.|Shanghai Engineering Research Center of Pharmaceutical Translation, 1278 Keyuan Road, Shanghai, 201203, P.R. China. yyli@scbit.org.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
mesh_terms: D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D004194:Disease / Q000235:genetics*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans
keywords: Differential coexpression analysis; Differential regulation; Disease similarity; Dysfunctional regulation mechanism; Human disease network