One important problem in genomic research is to identify genomic features such as gene expression data or DNA single nucleotide polymorphisms (SNPs) that are related to clinical phenotypes. Often these genomic data can be naturally divided into biologically meaningful groups such as genes belonging to the same pathways or SNPs within genes. In this paper, we propose group additive regression models and a group gradient descent boosting procedure for identifying groups of genomic features that are related to clinical phenotypes. Our simulation results show that by dividing the variables into appropriate groups, we can obtain better identification of the group features that are related to the phenotypes. In addition, the prediction mean square errors are also smaller than the component-wise boosting procedure. We demonstrate the application of the methods to pathway-based analysis of microarray gene expression data of breast cancer and gene-based genetic association analysis of type 1 diabetes. Results from analysis of two breast cancer data sets indicate that the pathways of Metalloendopeptidases (MMPs) and MMP inhibitors, as well as cell proliferation, cell growth and maintenance are important to breast cancer relapse and survival. Results from analysis of a set of nonsynonymous SNPs on chromosome 6 confirmed a few genes that are associated with type 1 diabetes.
Bioinformatics | Computational Biology
Luan, Yihui and Li, Hongzhe, "Group Additive Regression Models for Genomic Data Analysis" (August 2006). UPenn Biostatistics Working Papers. Working Paper 12.