Of mice and men: sparse statistical modeling in cardiovascular genomics. (English) Zbl 1129.62104

Summary: In high-throughput genomics, large-scale designed experiments are becoming common, and analysis approaches based on highly multivariate regression and ANOVA concepts are key tools. Shrinkage models of one form or another can provide comprehensive approaches to the problems of simultaneous inference that involve implicit multiple comparisons over the many, many parameters representing effects of design factors and covariates. We use such approaches here in a study of cardiovascular genomics. The primary experimental context concerns a carefully designed, and rich, gene expression study focused on gene-environment interactions, with the goal of identifying genes implicated in connection with disease states and known risk factors, and in generating expression signatures as proxies for such risk factors.
A coupled exploratory analysis investigates cross-species extrapolation of gene expression signatures, and how these mouse-model signatures translate to humans. The latter involves exploration of sparse latent factor analysis of human observational data and of how it relates to projected risk signatures derived in the animal models. The study also highlights a range of applied statistical and genomic data analysis issues, including model specification, computational questions and model-based correction of experimental artifacts in DNA microarray data.


62P10 Applications of statistics to biology and medical sciences; meta analysis
92C50 Medical applications (general)
62J10 Analysis of variance and covariance (ANOVA)
62J15 Paired and multiple comparisons; multiple testing
92C40 Biochemistry, molecular biology
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