Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

SUBMITTER: Wang Q

PROVIDER: S-EPMC4514922 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

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

Wang Quan Q Yu Hui H Zhao Zhongming Z Jia Peilin P

Bioinformatics (Oxford, England) 20150324 15

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 ...[more]

PMID: 25805723

Similar Datasets

dmGWAS: dense module searching for genome-wide association studies in protein-protein interaction networks.

Project description:MotivationAn important question that has emerged from the recent success of genome-wide association studies (GWAS) is how to detect genetic signals beyond single markers/genes in order to explore their combined effects on mediating complex diseases and traits. Integrative testing of GWAS association data with that from prior-knowledge databases and proteome studies has recently gained attention. These methodologies may hold promise for comprehensively examining the interactions between genes underlying the pathogenesis of complex diseases.MethodsHere, we present a dense module searching (DMS) method to identify candidate subnetworks or genes for complex diseases by integrating the association signal from GWAS datasets into the human protein-protein interaction (PPI) network. The DMS method extensively searches for subnetworks enriched with low P-value genes in GWAS datasets. Compared with pathway-based approaches, this method introduces flexibility in defining a gene set and can effectively utilize local PPI information.ResultsWe implemented the DMS method in an R package, which can also evaluate and graphically represent the results. We demonstrated DMS in two GWAS datasets for complex diseases, i.e. breast cancer and pancreatic cancer. For each disease, the DMS method successfully identified a set of significant modules and candidate genes, including some well-studied genes not detected in the single-marker analysis of GWA studies. Functional enrichment analysis and comparison with previously published methods showed that the genes we identified by DMS have higher association signal.AvailabilitydmGWAS package and documents are available at http://bioinfo.mc.vanderbilt.edu/dmGWAS.html.

| S-EPMC3008643 | biostudies-literature

STAMS: STRING-assisted module search for genome wide association studies and application to autism.

Project description:MotivationAnalyzing genome wide association data in the context of biological pathways helps us understand how genetic variation influences phenotype and increases power to find associations. However, the utility of pathway-based analysis tools is hampered by undercuration and reliance on a distribution of signal across all of the genes in a pathway. Methods that combine genome wide association results with genetic networks to infer the key phenotype-modulating subnetworks combat these issues, but have primarily been limited to network definitions with yes/no labels for gene-gene interactions. A recent method (EW_dmGWAS) incorporates a biological network with weighted edge probability by requiring a secondary phenotype-specific expression dataset. In this article, we combine an algorithm for weighted-edge module searching and a probabilistic interaction network in order to develop a method, STAMS, for recovering modules of genes with strong associations to the phenotype and probable biologic coherence. Our method builds on EW_dmGWAS but does not require a secondary expression dataset and performs better in six test cases.ResultsWe show that our algorithm improves over EW_dmGWAS and standard gene-based analysis by measuring precision and recall of each method on separately identified associations. In the Wellcome Trust Rheumatoid Arthritis study, STAMS-identified modules were more enriched for separately identified associations than EW_dmGWAS (STAMS P-value 3.0 × 10-4; EW_dmGWAS- P-value = 0.8). We demonstrate that the area under the Precision-Recall curve is 5.9 times higher with STAMS than EW_dmGWAS run on the Wellcome Trust Type 1 Diabetes data.Availability and implementationSTAMS is implemented as an R package and is freely available at https://simtk.org/projects/stams CONTACT: rbaltman@stanford.eduSupplementary information: Supplementary data are available at Bioinformatics online.

| S-EPMC5167061 | biostudies-literature

Weighted multiple testing procedures in genome-wide association studies.

Project description:Multiple testing procedures controlling the false discovery rate (FDR) are increasingly used in the context of genome wide association studies (GWAS), and weighted multiple testing procedures that incorporate covariate information are efficient to improve the power to detect associations. In this work, we evaluate some recent weighted multiple testing procedures in the specific context of GWAS through a simulation study. We also present a new efficient procedure called wBHa that prioritizes the detection of genetic variants with low minor allele frequencies while maximizing the overall detection power. The results indicate good performance of our procedure compared to other weighted multiple testing procedures. In particular, in all simulated settings, wBHa tends to outperform other procedures in detecting rare variants while maintaining good overall power. The use of the different procedures is illustrated with a real dataset.

| S-EPMC10276986 | biostudies-literature

Stochastic model search with binary outcomes for genome-wide association studies.

Project description:The spread of case-control genome-wide association studies (GWASs) has stimulated the development of new variable selection methods and predictive models. We introduce a novel Bayesian model search algorithm, Binary Outcome Stochastic Search (BOSS), which addresses the model selection problem when the number of predictors far exceeds the number of binary responses.Our method is based on a latent variable model that links the observed outcomes to the underlying genetic variables. A Markov Chain Monte Carlo approach is used for model search and to evaluate the posterior probability of each predictor.BOSS is compared with three established methods (stepwise regression, logistic lasso, and elastic net) in a simulated benchmark. Two real case studies are also investigated: a GWAS on the genetic bases of longevity, and the type 2 diabetes study from the Wellcome Trust Case Control Consortium. Simulations show that BOSS achieves higher precisions than the reference methods while preserving good recall rates. In both experimental studies, BOSS successfully detects genetic polymorphisms previously reported to be associated with the analyzed phenotypes.BOSS outperforms the other methods in terms of F-measure on simulated data. In the two real studies, BOSS successfully detects biologically relevant features, some of which are missed by univariate analysis and the three reference techniques.The proposed algorithm is an advance in the methodology for model selection with a large number of features. Our simulated and experimental results showed that BOSS proves effective in detecting relevant markers while providing a parsimonious model.

| S-EPMC3392850 | biostudies-literature

Genome-wide association studies of brain imaging data via weighted distance correlation.

Project description:MotivationImaging genetics is mainly used to reveal the pathogenesis of neuropsychiatric risk genes and understand the relationship between human brain structure, functional and individual differences. Increasingly, the brain-wide imaging phenotypes in voxels are available to test the association with genetic markers. A challenge with analyzing such data is their high dimensionality and complex relationships.ResultsTo tackle this challenge, we introduce a weighed distance correlation (wdCor) that can assess the association between genetic markers and voxel-based imaging data. Importantly, the wdCor test takes the voxel-based data as a whole multivariate phenotype, which preserves the spatial continuity and might enhance the power. Besides, an adaptive permutation procedure is introduced to determine the P-values of the wdCor test and also alleviate the computational burden in GWAS. In extensive simulation studies, wdCor achieves much better performances compared to the original distance correlation. We also successfully apply wdCor to conduct a large-scale analysis on data from the Alzheimer's disease neuroimaging project (ADNI).Availability and implementationOur wdCor method provides new research directions and ideas for multivariate analysis of high-dimensional data, it can also be used as a tool for scientific analysis of imaging genetics research in practical applications. The R package wdcor, and the code for reproducing all results in this article is available in Github: https://github.com/yangyuhui0129/wdcor.Supplementary informationSupplementary data are available at Bioinformatics online.

| S-EPMC7750969 | biostudies-literature

Highly cost-efficient genome-wide association studies using DNA pools and dense SNP arrays.

Project description:Genome-wide association (GWA) studies to map genes for complex traits are powerful yet costly. DNA-pooling strategies have the potential to dramatically reduce the cost of GWA studies. Pooling using Affymetrix arrays has been proposed and used but the efficiency of these arrays has not been quantified. We compared and contrasted Affymetrix Genechip HindIII and Illumina HumanHap300 arrays on the same DNA pools and showed that the HumanHap300 arrays are substantially more efficient. In terms of effective sample size, HumanHap300-based pooling extracts >80% of the information available with individual genotyping (IG). In contrast, Genechip HindIII-based pooling only extracts approximately 30% of the available information. With HumanHap300 arrays concordance with IG data is excellent. Guidance is given on best study design and it is shown that even after taking into account pooling error, one stage scans can be performed for >100-fold reduced cost compared with IG. With appropriately designed two stage studies, IG can provide confirmation of pooling results whilst still providing approximately 20-fold reduction in total cost compared with IG-based alternatives. The large cost savings with Illumina HumanHap300-based pooling imply that future studies need only be limited by the availability of samples and not cost.

| S-EPMC2346606 | biostudies-literature

An efficient weighted tag SNP-set analytical method in genome-wide association studies.

Project description:Single-nucleotide polymorphism (SNP)-set analysis in Genome-wide association studies (GWAS) has emerged as a research hotspot for identifying genetic variants associated with disease susceptibility. But most existing methods of SNP-set analysis are affected by the quality of SNP-set, and poor quality of SNP-set can lead to low power in GWAS.In this research, we propose an efficient weighted tag-SNP-set analytical method to detect the disease associations. In our method, we first design a fast algorithm to select a subset of SNPs (called tag SNP-set) from a given original SNP-set based on the linkage disequilibrium (LD) between SNPs, then assign a proper weight to each of the selected tag SNP respectively and test the joint effect of these weighted tag SNPs. The intensive simulation results show that the power of weighted tag SNP-set-based test is much higher than that of weighted original SNP-set-based test and that of un-weighted tag SNP-set-based test. We also compare the powers of the weighted tag SNP-set-based test based on four types of tag SNP-sets. The simulation results indicate the method of selecting tag SNP-set impacts the power greatly and the power of our proposed method is the highest.From the analysis of simulated replicated data sets, we came to a conclusion that weighted tag SNP-set-based test is a powerful SNP-set test in GWAS. We also designed a faster algorithm of selecting tag SNPs which include most of information of original SNP-set, and a better weighted function which can describe the status of each tag SNP in GWAS.

| S-EPMC4373116 | biostudies-literature

Genome-wide conditional search for epistatic disease-predisposing variants in human association studies.

Project description:Genome-wide search for new disease variants, based on well-established variants, has a long history in linkage analysis but is less well-known in genetic case-control association studies. We developed a simple yet highly efficient conditional search method that can find new variants, which are associated with a disease only through epistatic interaction with another variant and do not necessarily have a direct association effect. Our approach is analogous to partitioning of chi(2) in a hierarchical design, which is a well-established statistical technique. Applied to previously published data on age-related macular degeneration, our method found two single-nucleotide polymorphisms with genome-wide significant epistatic interaction that could not be found based only on direct main effects.

| S-EPMC2912644 | biostudies-literature

Using biological networks to search for interacting loci in genome-wide association studies.

Project description:Genome-wide association studies have identified a large number of single-nucleotide polymorphisms (SNPs) that individually predispose to diseases. However, many genetic risk factors remain unaccounted for. Proteins coded by genes interact in the cell, and it is most likely that certain variants mainly affect the phenotype in combination with other variants, termed epistasis. An exhaustive search for epistatic effects is computationally demanding, as several billions of SNP pairs exist for typical genotyping chips. In this study, the experimental knowledge on biological networks is used to narrow the search for two-locus epistasis. We provide evidence that this approach is computationally feasible and statistically powerful. By applying this method to the Wellcome Trust Case-Control Consortium data sets, we report four significant cases of epistasis between unlinked loci, in susceptibility to Crohn's disease, bipolar disorder, hypertension and rheumatoid arthritis.

| S-EPMC2986645 | biostudies-literature

Genome-wide association studies and gene expression profiles of rheumatoid arthritis: An analysis.

Project description:OBJECTIVES:The molecular mechanism of rheumatoid arthritis (RA) remains elusive. We conducted a protein-protein interaction network-based integrative analysis of genome-wide association studies (GWAS) and gene expression profiles of RA. METHODS:We first performed a dense search of RA-associated gene modules by integrating a large GWAS meta-analysis dataset (containing 5539 RA patients and 20 169 healthy controls), protein interaction network and gene expression profiles of RA synovium and peripheral blood mononuclear cells (PBMCs). Gene ontology (GO) enrichment analysis was conducted by DAVID. The protein association networks of gene modules were generated by STRING. RESULTS:For RA synovium, the top-ranked gene module is HLA-A, containing TAP2, HLA-A, HLA-C, TAPBP and LILRB1 genes. For RA PBMCs, the top-ranked gene module is GRB7, consisting of HLA-DRB5, HLA-DRA, GRB7, CD63 and KIT genes. Functional enrichment analysis identified three significant GO terms for RA synovium, including antigen processing and presentation of peptide antigen via major histocompatibility complex class I (false discovery rate (FDR) = 4.86 × 10 - 4), antigen processing and presentation of peptide antigen (FDR = 2.33 × 10 - 3) and eukaryotic translation initiation factor 4F complex (FDR = 2.52 × 10 - 2). CONCLUSION:This study reported several RA-associated gene modules and their functional association networks.Cite this article: X. Xiao, J. Hao, Y. Wen, W. Wang, X. Guo, F. Zhang. Genome-wide association studies and gene expression profiles of rheumatoid arthritis: an analysis. Bone Joint Res 2016;5:314-319. DOI: 10.1302/2046-3758.57.2000502.

| S-EPMC5005471 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data