Gene Set-based Analysis of Polymorphisms (GeSBAP)

Category Genomics>Genetic Data Analysis/Tools

Abstract GeSBAP is a novel web-based resource that can be used to check for pathway (or GO terms) associations to diseases (or any other trait) in genome-wide association analysis (GWAS) with Single Nucleotide Polymorphisms (SNPs) or Copy Number Variations (CNVs).

Searching directly for the association of pathways (or other types of functional modules) to phenotypic traits or diseases, instead of just analyzing SNPs independently, constitutes a novel perspective in polymorphisms' analysis inspired in systems biology.

As in other fields (e.g. microarray analysis) gene set-based analysis (GSA) has demonstrated its effectiveness in providing a testing framework much more advanced than the conventional one-gene-at-a- time testing scheme.

There is a great interest among the scientific community in strategies that increase the statistical power to find associations in GWAS.

The Gene Set-based Analysis of Polymorphisms (GeSBAP) web server can input lists of SNP or CNV identifiers arranged according to a parameter accounting for the association (P-value) and it returns a collection of biological processes significantly associated to the trait studied.

Lists of genes belonging to such processes can easily be obtained for further validation.

GeSBAP Input processing--

GeSBAP inputs a tab-delimited list of polymorphisms (SNP and/or CNV) along with the corresponding P-value of the association.

It is also possible to enter more processed data, such a list of genes with the corresponding P-value of association.

Any of the most common gene identifiers can be used given that GeSBAP uses internally, the INFRARED engine for gene ID conversion used in the Babelomics package (see G6G Abstract Number 20274).

Data can also be input in the format of the popular PLINK program, which performs the association test and obtains the corresponding list of P-values.

At present only human, mouse and rat SNPs can be used in GeSBAP.

The user can also choose to test one or several functional categories among Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCarta pathways (see G6G Abstract Number 20264).

Several filters can be applied to use subsets of any of these categories, which essentially involve filtering for maximum and minimum number of genes in the terms tested, filtering by keywords and, in the case of GO, filtering by levels in the GO hierarchy.

GeSBAP Testing strategy --

Given a list of genes ranked by any criteria, GSA is used to find enrichments of gene sets significantly associated to high (or low) values of rank.

Here, the ranking criterion for the genes is derived from the associations of the SNPs to the trait studied.

In particular, the program uses the -log (P-value) of the association test corresponding to the case-control comparison.

GeSBAP selects the polymorphisms (SNPs or CNVs) that map into genes or in their neighborhoods (±5 kb).

Among all the polymorphisms corresponding to each gene, the one with the highest association to the trait studied is taken as a proxy of the gene.

Then, all the genes represented in the GWAS (usually the complete genome) are mapped to the corresponding functional categories previously selected by the user and ranked accordingly to their proxy polymorphisms.

Finally, a GSA test is used to check for functional categories showing significant association to the trait studied.

The significant functional terms along with the corresponding P-values (adjusted for multiple testing) are listed in the output.

GeSBAP Output --

The output of GeSBAP provides a general overview on the 'functional categories' found as significantly associated to the trait studied.

A table including the significant functional categories along with their corresponding P-values and the genes included in each one is provided.

In addition, when Gene Ontology (GO) terms are being analyzed, a graphical representation of the significant terms within the GO hierarchy is also provided.

The GO viewer implemented in the Babelomics package is used for this purpose.

System Requirements

Web-based.

Manufacturer

Manufacturer Web Site GeSBAP

Price Contact manufacturer.

G6G Abstract Number 20492

G6G Manufacturer Number 102153