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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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Detalles Bibliográficos
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
Descripción
Sumario: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.