Network-based regularization for analysis of high-dimensional genomic data with group structure

In genetic association studies with high-dimensional genomic data, regularization procedures based on penalized likelihood are often applied to identify genes or genetic regions associated with diseases or traits. A network-based regularization procedure can utilize biological network information (such as genetic pathways and signaling pathways in genetic association studies) with an outstanding selection performance over other regularization procedures such as lasso and elastic-net. However, network-based regularization has a limitation because cannot be applied to high-dimension genomic data with a group structure. In this article, we propose to combine data dimension reduction techniques such as principal component analysis and a partial least square into network-based regularization for the analysis of high-dimensional genomic data with a group structure. The selection performance of the proposed method was evaluated by extensive simulation studies. The proposed method was also applied to real DNA methylation data generated from Illumina Infinium HumanMethylation27K BeadChip, where methylation beta values of around 20,000 CpG sites over 12,770 genes were compared between 123 ovarian cancer patients and 152 healthy controls. This analysis was also able to indicate a few cancer-related genes.