pulver: an R package for parallel ultra-rapid p-value computation for linear regression interaction terms

Abstract Background Genome-wide association studies allow us to understand the genetics of complex diseases. Human metabolism provides information about the disease-causing mechanisms, so it is usual to investigate the associations between genetic variants and metabolite levels. However, only consid...

Full description

Bibliographic Details
Main Authors: Sophie Molnos, Clemens Baumbach, Simone Wahl, Martina Müller-Nurasyid, Konstantin Strauch, Rui Wang-Sattler, Melanie Waldenberger, Thomas Meitinger, Jerzy Adamski, Gabi Kastenmüller, Karsten Suhre, Annette Peters, Harald Grallert, Fabian J. Theis, Christian Gieger
Format: Article
Language:English
Published: BMC 2017-09-01
Series:BMC Bioinformatics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12859-017-1838-y
_version_ 1819145192679145472
author Sophie Molnos
Clemens Baumbach
Simone Wahl
Martina Müller-Nurasyid
Konstantin Strauch
Rui Wang-Sattler
Melanie Waldenberger
Thomas Meitinger
Jerzy Adamski
Gabi Kastenmüller
Karsten Suhre
Annette Peters
Harald Grallert
Fabian J. Theis
Christian Gieger
author_facet Sophie Molnos
Clemens Baumbach
Simone Wahl
Martina Müller-Nurasyid
Konstantin Strauch
Rui Wang-Sattler
Melanie Waldenberger
Thomas Meitinger
Jerzy Adamski
Gabi Kastenmüller
Karsten Suhre
Annette Peters
Harald Grallert
Fabian J. Theis
Christian Gieger
author_sort Sophie Molnos
collection DOAJ
description Abstract Background Genome-wide association studies allow us to understand the genetics of complex diseases. Human metabolism provides information about the disease-causing mechanisms, so it is usual to investigate the associations between genetic variants and metabolite levels. However, only considering genetic variants and their effects on one trait ignores the possible interplay between different “omics” layers. Existing tools only consider single-nucleotide polymorphism (SNP)–SNP interactions, and no practical tool is available for large-scale investigations of the interactions between pairs of arbitrary quantitative variables. Results We developed an R package called pulver to compute p-values for the interaction term in a very large number of linear regression models. Comparisons based on simulated data showed that pulver is much faster than the existing tools. This is achieved by using the correlation coefficient to test the null-hypothesis, which avoids the costly computation of inversions. Additional tricks are a rearrangement of the order, when iterating through the different “omics” layers, and implementing this algorithm in the fast programming language C++. Furthermore, we applied our algorithm to data from the German KORA study to investigate a real-world problem involving the interplay among DNA methylation, genetic variants, and metabolite levels. Conclusions The pulver package is a convenient and rapid tool for screening huge numbers of linear regression models for significant interaction terms in arbitrary pairs of quantitative variables. pulver is written in R and C++, and can be downloaded freely from CRAN at https://cran.r-project.org/web/packages/pulver/ .
first_indexed 2024-12-22T12:54:08Z
format Article
id doaj.art-5050b8deacdc406baf1a8ec8049548a9
institution Directory Open Access Journal
issn 1471-2105
language English
last_indexed 2024-12-22T12:54:08Z
publishDate 2017-09-01
publisher BMC
record_format Article
series BMC Bioinformatics
spelling doaj.art-5050b8deacdc406baf1a8ec8049548a92022-12-21T18:25:10ZengBMCBMC Bioinformatics1471-21052017-09-011811810.1186/s12859-017-1838-ypulver: an R package for parallel ultra-rapid p-value computation for linear regression interaction termsSophie Molnos0Clemens Baumbach1Simone Wahl2Martina Müller-Nurasyid3Konstantin Strauch4Rui Wang-Sattler5Melanie Waldenberger6Thomas Meitinger7Jerzy Adamski8Gabi Kastenmüller9Karsten Suhre10Annette Peters11Harald Grallert12Fabian J. Theis13Christian Gieger14Research Unit of Molecular Epidemiology, Helmholtz Zentrum MünchenResearch Unit of Molecular Epidemiology, Helmholtz Zentrum MünchenResearch Unit of Molecular Epidemiology, Helmholtz Zentrum MünchenDepartment of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-UniversitätInstitute of Genetic Epidemiology, Helmholtz Zentrum MünchenResearch Unit of Molecular Epidemiology, Helmholtz Zentrum MünchenResearch Unit of Molecular Epidemiology, Helmholtz Zentrum MünchenInstitute of Human Genetics, Helmholtz Zentrum MünchenGerman Center for Diabetes Research (DZD)Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum MünchenInstitute of Bioinformatics and Systems Biology, Helmholtz Zentrum MünchenResearch Unit of Molecular Epidemiology, Helmholtz Zentrum MünchenResearch Unit of Molecular Epidemiology, Helmholtz Zentrum MünchenInstitute of Computational Biology, Helmholtz Zentrum MünchenResearch Unit of Molecular Epidemiology, Helmholtz Zentrum MünchenAbstract Background Genome-wide association studies allow us to understand the genetics of complex diseases. Human metabolism provides information about the disease-causing mechanisms, so it is usual to investigate the associations between genetic variants and metabolite levels. However, only considering genetic variants and their effects on one trait ignores the possible interplay between different “omics” layers. Existing tools only consider single-nucleotide polymorphism (SNP)–SNP interactions, and no practical tool is available for large-scale investigations of the interactions between pairs of arbitrary quantitative variables. Results We developed an R package called pulver to compute p-values for the interaction term in a very large number of linear regression models. Comparisons based on simulated data showed that pulver is much faster than the existing tools. This is achieved by using the correlation coefficient to test the null-hypothesis, which avoids the costly computation of inversions. Additional tricks are a rearrangement of the order, when iterating through the different “omics” layers, and implementing this algorithm in the fast programming language C++. Furthermore, we applied our algorithm to data from the German KORA study to investigate a real-world problem involving the interplay among DNA methylation, genetic variants, and metabolite levels. Conclusions The pulver package is a convenient and rapid tool for screening huge numbers of linear regression models for significant interaction terms in arbitrary pairs of quantitative variables. pulver is written in R and C++, and can be downloaded freely from CRAN at https://cran.r-project.org/web/packages/pulver/ .http://link.springer.com/article/10.1186/s12859-017-1838-yAlgorithmLinear regression interaction termSNP–CpG interactionSoftware
spellingShingle Sophie Molnos
Clemens Baumbach
Simone Wahl
Martina Müller-Nurasyid
Konstantin Strauch
Rui Wang-Sattler
Melanie Waldenberger
Thomas Meitinger
Jerzy Adamski
Gabi Kastenmüller
Karsten Suhre
Annette Peters
Harald Grallert
Fabian J. Theis
Christian Gieger
pulver: an R package for parallel ultra-rapid p-value computation for linear regression interaction terms
BMC Bioinformatics
Algorithm
Linear regression interaction term
SNP–CpG interaction
Software
title pulver: an R package for parallel ultra-rapid p-value computation for linear regression interaction terms
title_full pulver: an R package for parallel ultra-rapid p-value computation for linear regression interaction terms
title_fullStr pulver: an R package for parallel ultra-rapid p-value computation for linear regression interaction terms
title_full_unstemmed pulver: an R package for parallel ultra-rapid p-value computation for linear regression interaction terms
title_short pulver: an R package for parallel ultra-rapid p-value computation for linear regression interaction terms
title_sort pulver an r package for parallel ultra rapid p value computation for linear regression interaction terms
topic Algorithm
Linear regression interaction term
SNP–CpG interaction
Software
url http://link.springer.com/article/10.1186/s12859-017-1838-y
work_keys_str_mv AT sophiemolnos pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT clemensbaumbach pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT simonewahl pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT martinamullernurasyid pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT konstantinstrauch pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT ruiwangsattler pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT melaniewaldenberger pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT thomasmeitinger pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT jerzyadamski pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT gabikastenmuller pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT karstensuhre pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT annettepeters pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT haraldgrallert pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT fabianjtheis pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms
AT christiangieger pulveranrpackageforparallelultrarapidpvaluecomputationforlinearregressioninteractionterms