EW_dmGWAS: edge-weighted dense module search for genome-wide association studies and gene expression profiles

We previously developed dmGWAS to search for dense modules in a human protein-protein interaction (PPI) network; it has since become a popular tool for network-assisted analysis of genome-wide association studies (GWAS). dmGWAS weights nodes by using GWAS signals. Here, we introduce an upgraded algorithm, EW_dmGWAS, to boost GWAS signals in a node- and edge-weighted PPI network. In EW_dmGWAS, we utilize condition-specific gene expression profiles for edge weights. Specifically, differential gene co-expression is used to infer the edge weights. We applied EW_dmGWAS to two diseases and compared it with other relevant methods. The results suggest that EW_dmGWAS is more powerful in detecting disease-associated signals.

[1]  Bing Zhang,et al.  WebGestalt: an integrated system for exploring gene sets in various biological contexts , 2005, Nucleic Acids Res..

[2]  W. Willett,et al.  A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer , 2007, Nature Genetics.

[3]  Jianmin Wu,et al.  Integrated network analysis platform for protein-protein interactions , 2009, Nature Methods.

[4]  Judy H. Cho,et al.  Comparisons of multi‐marker association methods to detect association between a candidate region and disease , 2010, Genetic epidemiology.

[5]  P. Visscher,et al.  A versatile gene-based test for genome-wide association studies. , 2010, American journal of human genetics.

[6]  P. Jia,et al.  SZGR: a comprehensive schizophrenia gene resource , 2009, Molecular Psychiatry.

[7]  Hongyu Zhao,et al.  COSINE: COndition-SpecIfic sub-NEtwork identification using a global optimization method , 2011, Bioinform..

[8]  Wei Zheng,et al.  dmGWAS: dense module searching for genome-wide association studies in protein-protein interaction networks , 2011, Bioinform..

[9]  Aiden Corvin,et al.  Network-assisted investigation of combined causal signals from genome-wide association studies in schizophrenia. , 2012 .

[10]  Daniel E. Adkins,et al.  SNP-based analysis of neuroactive ligand–receptor interaction pathways implicates PGE2 as a novel mediator of antipsychotic treatment response: Data from the CATIE study , 2012, Schizophrenia Research.

[11]  Søren Brunak,et al.  MetaRanker 2.0: a web server for prioritization of genetic variation data , 2013, Nucleic Acids Res..

[12]  Chen-Ching Lin,et al.  Dynamic protein interaction modules in human hepatocellular carcinoma progression , 2013, BMC Systems Biology.

[13]  Judy H. Cho,et al.  Guilt by rewiring: gene prioritization through network rewiring in genome wide association studies. , 2014, Human molecular genetics.

[14]  Peilin Jia,et al.  Transcriptome Sequencing and Genome-wide Association Analyses Reveal Lysosomal Function and Actin Cytoskeleton Remodeling in Schizophrenia and Bipolar Disorder , 2014, Molecular Psychiatry.