Integration of gene expression, genome wide DNA methylation, and gene networks for clinical outcome prediction in ovarian cancer

Integrative clinical outcome prediction model called gene interaction regularized elastic net (GIREN) method is proposed in this paper. GIREN combines gene expression, methylation profiles, and gene interaction networks in order to reveal genomic and epigenomic features that bear important prognostic value. With GIREN, gene expression and DNA methylation profiles are first jointly analyzed in a linear regression model, and additional gene interaction network is simultaneously integrated as a regularizing penalty that follow an elastic net formulation. Such regularization also enforce sparsity in the solution so that features with prognostic values are automatically selected. To solve the regularized optimization, an iterative gradient descent algorithm is also developed. We applied GIREN to a set of 87 human ovarian cancer samples, which underwent a rigorous sample selection. The predicted outcome was used to group patients into high-risk vs. low-risk. Validation showed that GIREN outperformed other competing algorithms including SuperPCA.