In:
Bioinformatics, Oxford University Press (OUP), Vol. 32, No. 4 ( 2016-02-15), p. 549-556
Abstract:
Motivation: Despite numerous successful Genome-wide Association Studies (GWAS), detecting variants that have low disease risk still poses a challenge. GWAS may miss disease genes with weak genetic effects or strong epistatic effects due to the single-marker testing approach commonly used. GWAS may thus generate false negative or inconclusive results, suggesting the need for novel methods to combine effects of single nucleotide polymorphisms within a gene to increase the likelihood of fully characterizing the susceptibility gene. Results: We developed ancGWAS, an algebraic graph-based centrality measure that accounts for linkage disequilibrium in identifying significant disease sub-networks by integrating the association signal from GWAS data sets into the human protein–protein interaction (PPI) network. We validated ancGWAS using an association study result from a breast cancer data set and the simulation of interactive disease loci in the simulation of a complex admixed population, as well as pathway-based GWAS simulation. This new approach holds promise for deconvoluting the interactions between genes underlying the pathogenesis of complex diseases. Results obtained yield a novel central breast cancer sub-network of the human interactome implicated in the proteoglycan syndecan-mediated signaling events pathway which is known to play a major role in mesenchymal tumor cell proliferation, thus providing further insights into breast cancer pathogenesis. Availability and implementation: The ancGWAS package and documents are available at http://www.cbio.uct.ac.za/~emile/software.html Contact: emile.chimusa@uct.ac.za, Nicola.Mulder@uct.ac.za Supplementary information: Supplementary data are available at Bioinformatics online.
Type of Medium:
Online Resource
ISSN:
1367-4811
,
1367-4803
DOI:
10.1093/bioinformatics/btv619
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2016
detail.hit.zdb_id:
1468345-3
SSG:
12
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