Variable selection methods have been extensively developed for and applied to cancer genomics data to identify important omics features associated with complex disease traits, including cancer outcomes. However, the reliability and reproducibility of the findings are in question if valid inferential procedures are not available to quantify the uncertainty of the findings. In this article, we provide a gentle but systematic review of high-dimensional frequentist and Bayesian inferential tools under sparse models which can yield uncertainty quantification measures, including confidence (or Bayesian credible) intervals, p values and false discovery rates (FDR). Connections in high-dimensional inferences between the two realms have been fully exploited under the “unpenalized loss function + penalty term” formulation for regularization methods and the “likelihood function × shrinkage prior” framework for regularized Bayesian analysis. In particular, we advocate for robust Bayesian variable selection in cancer genomics studies due to its ability to accommodate disease heterogeneity in the form of heavy-tailed errors and structured sparsity while providing valid statistical inference. The numerical results show that robust Bayesian analysis incorporating exact sparsity has yielded not only superior estimation and identification results but also valid Bayesian credible intervals under nominal coverage probabilities compared with alternative methods, especially in the presence of heavy-tailed model errors and outliers.

In high-throughput genetics studies, an important aim is to identify gene–environment interactions associated with the clinical outcomes. Recently, multiple marginal penalization methods have been developed and shown to be effective in G×E studies. However, within the Bayesian framework, marginal variable selection has not received much attention. In this study, we propose a novel marginal Bayesian variable selection method for G×E studies. In particular, our marginal Bayesian method is robust to data contamination and outliers in the outcome variables. With the incorporation of spike-and-slab priors, we have implemented the Gibbs sampler based on Markov Chain Monte Carlo (MCMC). The proposed method outperforms a number of alternatives in extensive simulation studies. The utility of the marginal robust Bayesian variable selection method has been further demonstrated in the case studies using data from the Nurse Health Study (NHS). Some of the identified main and interaction effects from the real data analysis have important biological implications.

Gene-environment (G×E) interaction is critical for understanding the genetic basis of complex disease beyond genetic and environment main effects. In addition to existing tools for interaction studies, penalized variable selection emerges as a promising alternative for dissecting G×E interactions. Despite the success, variable selection is limited in terms of accounting for multidimensional measurements. Published variable selection methods cannot accommodate structured sparsity in the framework of integrating multiomics data for disease outcomes. In this paper, we have developed a novel variable selection method in order to integrate multi-omics measurements in G×E interaction studies. Extensive studies have already revealed that analyzing omics data across multi-platforms is not only sensible biologically, but also resulting in improved identification and prediction performance. Our integrative model can efficiently pinpoint important regulators of gene expressions through sparse dimensionality reduction, and link the disease outcomes to multiple effects in the integrative G×E studies through accommodating a sparse bi-level structure. The simulation studies show the integrative model leads to better identification of G×E interactions and regulators than alternative methods. In two G×E lung cancer studies with high dimensional multi-omics data, the integrative model leads to an improved prediction and findings with important biological implications.

In longitudinal studies, repeated measure analysis of variance (ANOVA) is a classical analysis where selecting important main and interaction effects for accurate estimation and prediction is among one of its central goals. With high-dimensional genetic factors, ANOVA leads to a sparse longitudinal gene–environment (⁠ $G×E$⁠) interaction problem that has not been thoroughly investigated so far, partially due to the challenges to incorporate robustness against skewed phenotypic measurements, intra-cluster correlations among longitudinal observations, and structured sparsity arising from the ANOVA design. We have developed a novel robust sparse Bayesian mixed model to tackle these challenges. Outliers and inter-relatedness among repeated measurements can be efficiently accommodated. Meanwhile, the proposed model conducts robust Bayesian variable selection accounting for main and interaction effects via structured spike-and-slab priors. We have developed Gibbs samplers and MCMC algorithms for fast computation and posterior inference. The advantage of the proposed method over benchmarks in variable selection and estimation has been established through extensive simulations. In the case study, we have analysed longitudinal lipidomics data with repeatedly measured body weight of CD-1 mice from a cancer prevention study. The proposed model has identified main and interactions with important implications and led to better prediction performance over alternative methods.