Article (Scientific journals)
gammaMAXT: a fast multiple-testing correction algorithm
Van Lishout, François; Gadaleta, Francesco; Moore, Jason H. et al.
2015In BioData Mining, 8 (36)
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Keywords :
Multiple testing; Genome-wide interaction studies; MaxT; Gamma distribution; SNP-environment interactions; 3-order interactions; Algorithmic
Abstract :
[en] Background: The purpose of the maxT algorithm is to provide a significance test algorithm that controls the family-wise error rate (FWER) during simultaneous hypothesis testing. However, the requirements in terms of computing time and memory of this procedure are proportional to the number of investigated hypotheses. The memory issue has been solved in 2013 by Van Lishout’s implementation of MaxT, which makes the memory usage independent from the size of the dataset. This algorithm is implemented in MBMDR-3.0.3, a software that is able to identify genetic interactions, for a variety of SNP-SNP based epistasis models effectively. On the other hand, that implementation turned out to be less suitable for genome-wide interaction analysis studies, due to the prohibitive computational burden. Results: In this work we introduce gammaMAXT, a novel implementation of the maxT algorithm for multiple testing correction. The algorithm was implemented in software MBMDR-4.2.2, as part of the MB-MDR framework to screen for SNP-SNP, SNP-environment or SNP-SNP-environment interactions at a genome-wide level. We show that, in the absence of interaction effects, test-statistics produced by the MB-MDR methodology follow a mixture distribution with a point mass at zero and a shifted gamma distribution for the top 10 % of the strictly positive values. We show that the gammaMAXT algorithm has a power comparable to MaxT and maintains FWER, but requires less computational resources and time. We analyze a dataset composed of 106 SNPs and 1000 individuals within one day on a 256-core computer cluster. The same analysis would take about 104 times longer with MBMDR-3.0.3. Conclusions: These results are promising for future GWAIs.However, the proposed gammaMAXT algorithm offers a general significance assessment and multiple testing approach, applicable to any context that requires performing hundreds of thousands of tests. It offers new perspectives for fast and efficient permutation-based significance assessment in large-scale (integrated) omics studies.
Disciplines :
Computer science
Author, co-author :
Van Lishout, François ;  Université de Liège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Dép. d'électric., électron. et informat. (Inst.Montefiore)
Gadaleta, Francesco ;  Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Dép. d'électric., électron. et informat. (Inst.Montefiore)
Moore, Jason H.;  University of Pennsylvania, Philadelphia, USA > Institute for Biomedical Informatics > Institute for Biomedical Informatics
Wehenkel, Louis  ;  Université de Liège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Systèmes et modélisation
Van Steen, Kristel  ;  Université de Liège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique
Language :
English
Title :
gammaMAXT: a fast multiple-testing correction algorithm
Publication date :
20 November 2015
Journal title :
BioData Mining
eISSN :
1756-0381
Publisher :
BioMed Central, London, United Kingdom
Volume :
8
Issue :
36
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 15 January 2016

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