INTERSNP: genome-wide interaction analysis guided by a priori information

Herold, Christine; Steffens, Michael; Brockschmidt, Felix F.; Baur, Max P.; Becker, Tim

doi:10.1093/bioinformatics/btp596

Cited by 132 publications

(121 citation statements)

References 19 publications

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“…It should be noted that dedicated software, such as INTERSNP (http://intersnp.meb. uni-bonn.de), 9 is considerably faster for this second pass than pure R. The quoted figure of 8.5Â10 6 interaction pairs should be achieved between 1 or 2 hours using INTERSNP. A complete genome-wide association analysis with INTERSNP on a single core would be in the order of a year.…”

Section: Epiblaster Fast Gpu-based Epistasis T Kam-thong Et Almentioning

confidence: 84%

EPIBLASTER-fast exhaustive two-locus epistasis detection strategy using graphical processing units

et al. 2010

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Detection of epistatic interaction between loci has been postulated to provide a more in-depth understanding of the complex biological and biochemical pathways underlying human diseases. Studying the interaction between two loci is the natural progression following traditional and well-established single locus analysis. However, the added costs and time duration required for the computation involved have thus far deterred researchers from pursuing a genome-wide analysis of epistasis. In this paper, we propose a method allowing such analysis to be conducted very rapidly. The method, dubbed EPIBLASTER, is applicable to case-control studies and consists of a two-step process in which the difference in Pearson's correlation coefficients is computed between controls and cases across all possible SNP pairs as an indication of significant interaction warranting further analysis. For the subset of interactions deemed potentially significant, a second-stage analysis is performed using the likelihood ratio test from the logistic regression to obtain the P-value for the estimated coefficients of the individual effects and the interaction term. The algorithm is implemented using the parallel computational capability of commercially available graphical processing units to greatly reduce the computation time involved. In the current setup and example data sets (211 cases, 222 controls, 299468 SNPs; and 601 cases, 825 controls, 291095 SNPs), this coefficient evaluation stage can be completed in roughly 1 day. Our method allows for exhaustive and rapid detection of significant SNP pair interactions without imposing significant marginal effects of the single loci involved in the pair.

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Section: Epiblaster Fast Gpu-based Epistasis T Kam-thong Et Almentioning

confidence: 84%

EPIBLASTER-fast exhaustive two-locus epistasis detection strategy using graphical processing units

et al. 2010

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“…11 To this purpose and also to test for deviations from Hardy-Weinberg equilibrium, we used the implementation in the genetic analysis software INTERSNP. 12 For the analysis of deletions, we used Fisher's exact test for 2 Â 2 contingency tables and its implementation in R (The R Project for Statistical Computing, http://www.r-project.org/). All variants analyzed in this study were in Hardy-Weinberg equilibrium.…”

Section: Association Analysismentioning

confidence: 99%

Variants in the 3′UTR of SNCA do not affect miRNA-433 binding and alpha-synuclein expression

et al. 2012

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Alpha-synuclein (SNCA) is a major risk gene for Parkinson's disease (PD) and increased SNCA gene dosage results in a parkinsonian syndrome in affected families. Regulatory regions relevant for SNCA expression include the 3 0 untranslated region (UTR), which among other regulatory elements contains several micro-RNA-binding sites. Interestingly, variants located in the 3 0 region of SNCA have been associated with PD in two genome-wide association studies. To test whether private mutations in this region contribute to PD, we sequenced the 3 0 UTR of SNCA in 1285 PD patients and 1120 age/sex-matched healthy controls. We found two rare variants, the one corresponding to the single nucleotide polymorphism rs145304567 and the novel variant c.*1004_1008delTTTTT. Although rs145304567 affects the putative-binding site of microRNA (miRNA) -433, the allele distribution was similar in PD patients and controls, and the expression of SNCA mRNA was not related to the genotype. Furthermore, a regulatory effect of miRNA-433 on SNCA expression levels was not detected.

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“…In this work, the computation time of BOOST is compared with that of Plink [11] and INTERSNP [17] on small dataset sizes (5,000 individuals and 1,000, 5,000 and 10,000 SNPs). On these smaller sizes of data the ACO-Tabu search algorithm can store all of the SNPs in the tabu list and therefore can test all the pairs of SNPs in computation times shown in Table III (The 10,000 first SNPs of chromosome 1 of the T2D dataset were used for this experiment).…”

Section: B Methods Comparisonsmentioning

confidence: 99%

“…Furthermore, an approach for genome-wide interaction analysis of case-control SNP data and quantitative traits, called INTERSNP, is presented in [17]. Among the filter approaches, one of the most popular tools for exploring gene-gene interactions in GWAS is BOOST [18].…”

mentioning

confidence: 99%

An Ant Colony Optimization and Tabu List Approach to the Detection of Gene-Gene Interactions in Genome-Wide Association Studies [Research Frontier]

Sapin

Keedwell

Frayling

2015

IEEE Comput. Intell. Mag.

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In this paper, a novel ant colony optimisation and tabu list approach for the discovery of gene-gene interactions in genome-wide association study data is proposed. The method is tested on a number of diseases drawn from the large established database, the Wellcome Trust Case Control Consortium which contains hundreds of thousands of small DNA changes known as single nucleotide polymorphisms. To analyse full scale genome-wide association study data, the standard ant colony optimisation algorithm has been adapted, with tournament path selection, a subset based approach, and tabu list included in the algorithm. These modifications, in addition to the use of a statistical test of significance of single nucleotide polymorphism interactions as a fitness function, greatly increase execution speeds and permit the discovery of combinations of single nucleotide polymorphisms that can discriminate cases and controls. The methodology is applied to several large-scale genome-wide association study disease datasets namely, inflammatory bowel disease, rheumatoid arthritis, type I diabetes and type II diabetes patients to discover putative gene-gene interactions in reasonable time on modest hardware.

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INTERSNP: genome-wide interaction analysis guided by a priori information

Abstract: herold@imbie.meb.uni-bonn.de; becker@imbie.meb.uni-bonn.de.

Cited by 132 publications

References 19 publications

EPIBLASTER-fast exhaustive two-locus epistasis detection strategy using graphical processing units

EPIBLASTER-fast exhaustive two-locus epistasis detection strategy using graphical processing units

Variants in the 3′UTR of SNCA do not affect miRNA-433 binding and alpha-synuclein expression

An Ant Colony Optimization and Tabu List Approach to the Detection of Gene-Gene Interactions in Genome-Wide Association Studies [Research Frontier]

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