A whitening approach to probabilistic canonical correlation analysis for omics data integration

Abstract: Background: Canonical correlation analysis (CCA) is a classic statistical tool for investigating complex multivariate data. Correspondingly, it has found many diverse applications, ranging from molecular biology and medicine to social science and finance. Intriguingly, despite the importance and pervasiveness of CCA, only recently a probabilistic understanding of CCA is developing, moving from an algorithmic to a model-based perspective and enabling its application to large-scale settings. Results: Here, we revisit CCA from the perspective of statistical whitening of random variables and propose a simple yet flexible probabilistic model for CCA in the form of a two-layer latent variable generative model. The advantages of this variant of probabilistic CCA include non-ambiguity of the latent variables, provisions for negative canonical correlations, possibility of non-normal generative variables, as well as ease of interpretation on all levels of the model. In addition, we show that it lends itself to computationally efficient estimation in high-dimensional settings using regularized inference. We test our approach to CCA analysis in simulations and apply it to two omics data sets illustrating the integration of gene expression data, lipid concentrations and methylation levels. Conclusions: Our whitening approach to CCA provides a unifying perspective on CCA, linking together sphering procedures, multivariate regression and corresponding probabilistic generative models. Furthermore, we offer an efficient computer implementation in the "whitening" R package available at https://CRAN.R-project.org/package=whitening .