Network-constrained regularization and variable selection for analysis of genomic data

Simulation studies indicated that the method is quite effective in identifying genes and subnetworks that are related to disease and has higher sensitivity than the commonly used procedures that do not use the pathway structure information. Application to one glioblastoma microarray gene-expression dataset identified several subnetworks on several of the Kyoto Encyclopedia of Genes and Genomes (KEGG) transcriptional pathways that are related to survival from glioblastoma, many of which were supported by published literatures.

The proposed network-constrained regularization procedure efficiently utilizes the known pathway structures in identifying the relevant genes and the subnetworks that might be related to phenotype in a general regression framework. As more biological networks are identified and documented in databases, the proposed method should find more applications in identifying the subnetworks that are related to diseases and other biological processes.