Fast and accurate exhaustive higher-order epistasis search with BitEpi

Abstract Complex genetic diseases may be modulated by a large number of epistatic interactions affecting a polygenic phenotype. Identifying these interactions is difficult due to computational complexity, especially in the case of higher-order interactions where more than two genomic variants are in...

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Autores principales:	Arash Bayat, Brendan Hosking, Yatish Jain, Cameron Hosking, Milindi Kodikara, Daniel Reti, Natalie A. Twine, Denis C. Bauer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/820c98a27dfb45869dc930045658a0cc
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spelling	oai:doaj.org-article:820c98a27dfb45869dc930045658a0cc2021-12-02T17:06:32ZFast and accurate exhaustive higher-order epistasis search with BitEpi10.1038/s41598-021-94959-y2045-2322https://doaj.org/article/820c98a27dfb45869dc930045658a0cc2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94959-yhttps://doaj.org/toc/2045-2322Abstract Complex genetic diseases may be modulated by a large number of epistatic interactions affecting a polygenic phenotype. Identifying these interactions is difficult due to computational complexity, especially in the case of higher-order interactions where more than two genomic variants are involved. In this paper, we present BitEpi, a fast and accurate method to test all possible combinations of up to four bi-allelic variants (i.e. Single Nucleotide Variant or SNV for short). BitEpi introduces a novel bitwise algorithm that is 1.7 and 56 times faster for 3-SNV and 4-SNV search, than established software. The novel entropy statistic used in BitEpi is 44% more accurate to identify interactive SNVs, incorporating a p-value-based significance testing. We demonstrate BitEpi on real world data of 4900 samples and 87,000 SNPs. We also present EpiExplorer to visualize the potentially large number of individual and interacting SNVs in an interactive Cytoscape graph. EpiExplorer uses various visual elements to facilitate the discovery of true biological events in a complex polygenic environment.Arash BayatBrendan HoskingYatish JainCameron HoskingMilindi KodikaraDaniel RetiNatalie A. TwineDenis C. BauerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arash Bayat Brendan Hosking Yatish Jain Cameron Hosking Milindi Kodikara Daniel Reti Natalie A. Twine Denis C. Bauer Fast and accurate exhaustive higher-order epistasis search with BitEpi
description	Abstract Complex genetic diseases may be modulated by a large number of epistatic interactions affecting a polygenic phenotype. Identifying these interactions is difficult due to computational complexity, especially in the case of higher-order interactions where more than two genomic variants are involved. In this paper, we present BitEpi, a fast and accurate method to test all possible combinations of up to four bi-allelic variants (i.e. Single Nucleotide Variant or SNV for short). BitEpi introduces a novel bitwise algorithm that is 1.7 and 56 times faster for 3-SNV and 4-SNV search, than established software. The novel entropy statistic used in BitEpi is 44% more accurate to identify interactive SNVs, incorporating a p-value-based significance testing. We demonstrate BitEpi on real world data of 4900 samples and 87,000 SNPs. We also present EpiExplorer to visualize the potentially large number of individual and interacting SNVs in an interactive Cytoscape graph. EpiExplorer uses various visual elements to facilitate the discovery of true biological events in a complex polygenic environment.
format	article
author	Arash Bayat Brendan Hosking Yatish Jain Cameron Hosking Milindi Kodikara Daniel Reti Natalie A. Twine Denis C. Bauer
author_facet	Arash Bayat Brendan Hosking Yatish Jain Cameron Hosking Milindi Kodikara Daniel Reti Natalie A. Twine Denis C. Bauer
author_sort	Arash Bayat
title	Fast and accurate exhaustive higher-order epistasis search with BitEpi
title_short	Fast and accurate exhaustive higher-order epistasis search with BitEpi
title_full	Fast and accurate exhaustive higher-order epistasis search with BitEpi
title_fullStr	Fast and accurate exhaustive higher-order epistasis search with BitEpi
title_full_unstemmed	Fast and accurate exhaustive higher-order epistasis search with BitEpi
title_sort	fast and accurate exhaustive higher-order epistasis search with bitepi
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/820c98a27dfb45869dc930045658a0cc
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Fast and accurate exhaustive higher-order epistasis search with BitEpi

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