concerted perturbation observed in a hub network in alzheimer’s disease共同扰动观察阿尔茨海默病中心网络.pdfVIP

Concerted Perturbation Observed in a Hub Network in Alzheimer’s Disease 1,2 1,2 1 1,2 3 1,3 Dapeng Liang , Guangchun Han , Xuemei Feng , Jiya Sun , Yong Duan *, Hongxing Lei * 1 CAS key laboratory of genome sciences and information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China, 2 Graduate University, Chinese Academy of Sciences, Beijing, China, 3 UC Davis Genome Center and Department of Biomedical Engineering, University of California Davis, Davis, California, United States of America Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease involving the alteration of gene expression at the whole genome level. Genome-wide transcriptional profiling of AD has been conducted by many groups on several relevant brain regions. However, identifying the most critical dys-regulated genes has been challenging. In this work, we addressed this issue by deriving critical genes from perturbed subnetworks. Using a recent microarray dataset on six brain regions, we applied a heaviest induced subgraph algorithm with a modular scoring function to reveal the significantly perturbed subnetwork in each brain region. These perturbed subnetworks were found to be significantly overlapped with each other. Furthermore, the hub genes from these perturbed subnetworks formed a connected hub network consisting of 136 genes. Comparison between AD and several related diseases demonstrated that the hub network was robustly and specifically perturbed in AD. In addition, strong correlation between the expression level of these hub genes and indicators of AD severity suggested that this hub network can partially reflect AD progression