Dataset Information

Bayesian mixture modeling of gene-environment and gene-gene interactions.

ABSTRACT: With the advent of rapid and relatively cheap genotyping technologies there is now the opportunity to attempt to identify gene-environment and gene-gene interactions when the number of genes and environmental factors is potentially large. Unfortunately the dimensionality of the parameter space leads to a computational explosion in the number of possible interactions that may be investigated. The full model that includes all interactions and main effects can be unstable, with wide confidence intervals arising from the large number of estimated parameters. We describe a hierarchical mixture model that allows all interactions to be investigated simultaneously, but assumes the effects come from a mixture prior with two components, one that reflects small null effects and the second for epidemiologically significant effects. Effects from the former are effectively set to zero, hence increasing the power for the detection of real signals. The prior framework is very flexible, which allows substantive information to be incorporated into the analysis. We illustrate the methods first using simulation, and then on data from a case-control study of lung cancer in Central and Eastern Europe.

SUBMITTER: Wakefield J

PROVIDER: S-EPMC2796715 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Publications

Bayesian mixture modeling of gene-environment and gene-gene interactions.

Wakefield Jon J De Vocht Frank F Hung Rayjean J RJ

Genetic epidemiology 20100101 1

With the advent of rapid and relatively cheap genotyping technologies there is now the opportunity to attempt to identify gene-environment and gene-gene interactions when the number of genes and environmental factors is potentially large. Unfortunately the dimensionality of the parameter space leads to a computational explosion in the number of possible interactions that may be investigated. The full model that includes all interactions and main effects can be unstable, with wide confidence inte ...[more]

PMID: 19492346

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Project description:BackgroundInference of gene networks typically relies on measurements across a wide range of conditions or treatments. Although one network structure is predicted, the relationship between genes could vary across conditions. A comprehensive approach to infer general and condition-dependent gene networks was evaluated. This approach integrated Bayesian network and Gaussian mixture models to describe continuous microarray gene expression measurements, and three gene networks were predicted.ResultsThe first reconstructions of a circadian rhythm pathway in honey bees and an adherens junction pathway in mouse embryos were obtained. In addition, general and condition-specific gene relationships, some unexpected, were detected in these two pathways and in a yeast cell-cycle pathway. The mixture Bayesian network approach identified all (honey bee circadian rhythm and mouse adherens junction pathways) or the vast majority (yeast cell-cycle pathway) of the gene relationships reported in empirical studies. Findings across the three pathways and data sets indicate that the mixture Bayesian network approach is well-suited to infer gene pathways based on microarray data. Furthermore, the interpretation of model estimates provided a broader understanding of the relationships between genes. The mixture models offered a comprehensive description of the relationships among genes in complex biological processes or across a wide range of conditions. The mixture parameter estimates and corresponding odds that the gene network inferred for a sample pertained to each mixture component allowed the uncovering of both general and condition-dependent gene relationships and patterns of expression.ConclusionThis study demonstrated the two main benefits of learning gene pathways using mixture Bayesian networks. First, the identification of the optimal number of mixture components supported by the data offered a robust approach to infer gene relationships and estimate gene expression profiles. Second, the classification of conditions and observations into groups that support particular mixture components helped to uncover both gene relationships that are unique or common across conditions. Results from the application of mixture Bayesian networks substantially augmented the understanding of gene networks and demonstrated the added-value of this methodology to infer gene networks.

Dataset Information

Bayesian mixture modeling of gene-environment and gene-gene interactions.

Publications

Bayesian mixture modeling of gene-environment and gene-gene interactions.

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