Fast and accurate exhaustive higher-order epistasis search with BitEpi

Arash Bayat; Brendan Hosking; Yatish Jain; Cameron Hosking; Milindi Kodikara; Daniel Reti; Natalie A. Twine; Denis C. Bauer

doi:10.1038/s41598-021-94959-y

Fast and accurate exhaustive higher-order epistasis search with BitEpi

Arash Bayat, Brendan Hosking, Yatish Jain, Cameron Hosking, Milindi Kodikara, Daniel Reti, Natalie A. Twine, Denis C. Bauer^*

^*Corresponding author for this work

Applied BioSciences

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

72 Downloads (Pure)

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.

Original language	English
Article number	15923
Pages (from-to)	1-12
Number of pages	12
Journal	Scientific Reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-94959-y
Publication status	Published - 5 Aug 2021

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Access to Document

10.1038/s41598-021-94959-y

Publisher version (open access)Final published version, 1.7 MBLicence: CC BY

Cite this

@article{1c2aaab4a6ad490dadad84028323a911,

title = "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 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.",

author = "Arash Bayat and Brendan Hosking and Yatish Jain and Cameron Hosking and Milindi Kodikara and Daniel Reti and Twine, {Natalie A.} and Bauer, {Denis C.}",

note = "Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher. ",

year = "2021",

month = aug,

day = "5",

doi = "10.1038/s41598-021-94959-y",

language = "English",

volume = "11",

pages = "1--12",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Springer, Springer Nature",

number = "1",

}

TY - JOUR

T1 - Fast and accurate exhaustive higher-order epistasis search with BitEpi

AU - Bayat, Arash

AU - Hosking, Brendan

AU - Jain, Yatish

AU - Hosking, Cameron

AU - Kodikara, Milindi

AU - Reti, Daniel

AU - Twine, Natalie A.

AU - Bauer, Denis C.

N1 - Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2021/8/5

Y1 - 2021/8/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85111965657&partnerID=8YFLogxK

U2 - 10.1038/s41598-021-94959-y

DO - 10.1038/s41598-021-94959-y

M3 - Article

C2 - 34354094

AN - SCOPUS:85111965657

SN - 2045-2322

VL - 11

SP - 1

EP - 12

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 15923

ER -

Fast and accurate exhaustive higher-order epistasis search with BitEpi

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this