Support Vector Machines with Disease-gene-centric Network Penalty for High Dimensional Microarray Data.

Abstract

With the availability of genetic pathways or networks and accumulating knowledge on genes with variants predisposing to diseases (disease genes), we propose a disease-gene-centric support vector machine (DGC-SVM) that directly incorporates these two sources of prior information into building microarray-based classifiers for binary classification problems. DGC-SVM aims to detect the genes clustering together and around some key disease genes in a gene network. To achieve this goal, we propose a penalty over suitably defined groups of genes. A hierarchy is imposed on an undirected gene network to facilitate the definition of such gene groups. Our proposed DGC-SVM utilizes the hinge loss penalized by a sum of the L(infinity)-norm being applied to each group. The simulation studies show that DGC-SVM not only detects more disease genes along pathways than the existing standard SVM and SVM with an L(1)-penalty (L1-SVM), but also captures disease genes that potentially affect the outcome only weakly. Two real data applications demonstrate that DGC-SVM improves gene selection with predictive performance comparable to the standard-SVM and L1-SVM. The proposed method has the potential to be an effective classification tool that encourages gene selection along paths to or clustering around known disease genes for microarray data.