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An investigation of gene-gene interactions in dose-response studies with Bayesian nonparametrics

BACKGROUND: Best practice for statistical methodology in cell-based dose-response studies has yet to be established. We examine the ability of MANOVA to detect trait-associated genetic loci in the presence of gene-gene interactions. We present a novel Bayesian nonparametric method designed to detect...

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Autores principales: Beam, Andrew L, Motsinger-Reif, Alison A, Doyle, Jon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330980/
https://www.ncbi.nlm.nih.gov/pubmed/25691918
http://dx.doi.org/10.1186/s13040-015-0039-3
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author Beam, Andrew L
Motsinger-Reif, Alison A
Doyle, Jon
author_facet Beam, Andrew L
Motsinger-Reif, Alison A
Doyle, Jon
author_sort Beam, Andrew L
collection PubMed
description BACKGROUND: Best practice for statistical methodology in cell-based dose-response studies has yet to be established. We examine the ability of MANOVA to detect trait-associated genetic loci in the presence of gene-gene interactions. We present a novel Bayesian nonparametric method designed to detect such interactions. RESULTS: MANOVA and the Bayesian nonparametric approach show good ability to detect trait-associated genetic variants under various possible genetic models. It is shown through several sets of analyses that this may be due to marginal effects being present, even if the underlying genetic model does not explicitly contain them. CONCLUSIONS: Understanding how genetic interactions affect drug response continues to be a critical goal. MANOVA and the novel Bayesian framework present a trade-off between computational complexity and model flexibility.
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spelling pubmed-43309802015-02-18 An investigation of gene-gene interactions in dose-response studies with Bayesian nonparametrics Beam, Andrew L Motsinger-Reif, Alison A Doyle, Jon BioData Min Methodology BACKGROUND: Best practice for statistical methodology in cell-based dose-response studies has yet to be established. We examine the ability of MANOVA to detect trait-associated genetic loci in the presence of gene-gene interactions. We present a novel Bayesian nonparametric method designed to detect such interactions. RESULTS: MANOVA and the Bayesian nonparametric approach show good ability to detect trait-associated genetic variants under various possible genetic models. It is shown through several sets of analyses that this may be due to marginal effects being present, even if the underlying genetic model does not explicitly contain them. CONCLUSIONS: Understanding how genetic interactions affect drug response continues to be a critical goal. MANOVA and the novel Bayesian framework present a trade-off between computational complexity and model flexibility. BioMed Central 2015-02-06 /pmc/articles/PMC4330980/ /pubmed/25691918 http://dx.doi.org/10.1186/s13040-015-0039-3 Text en © Beam et al.; licensee BioMed Central. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Methodology
Beam, Andrew L
Motsinger-Reif, Alison A
Doyle, Jon
An investigation of gene-gene interactions in dose-response studies with Bayesian nonparametrics
title An investigation of gene-gene interactions in dose-response studies with Bayesian nonparametrics
title_full An investigation of gene-gene interactions in dose-response studies with Bayesian nonparametrics
title_fullStr An investigation of gene-gene interactions in dose-response studies with Bayesian nonparametrics
title_full_unstemmed An investigation of gene-gene interactions in dose-response studies with Bayesian nonparametrics
title_short An investigation of gene-gene interactions in dose-response studies with Bayesian nonparametrics
title_sort investigation of gene-gene interactions in dose-response studies with bayesian nonparametrics
topic Methodology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330980/
https://www.ncbi.nlm.nih.gov/pubmed/25691918
http://dx.doi.org/10.1186/s13040-015-0039-3
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