title: Concerted perturbation observed in a hub network in Alzheimer's disease.
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. More importantly, this hub network reflected the adaptation of neurons to the AD-specific microenvironment through a variety of adjustments, including reduction of neuronal and synaptic activities and alteration of survival signaling. Therefore, it is potentially useful for the development of biomarkers and network medicine for AD.
authors: CAS key laboratory of genome sciences and information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors: Dapeng
authors: D
authors: Liang
authors: Guangchun
authors: G
authors: Han
authors: Xuemei
authors: X
authors: Feng
authors: Jiya
authors: J
authors: Sun
authors: Yong
authors: Y
authors: Duan
authors: Hongxing
authors: H
authors: Lei
mesh_terms: D000375:Aging / Q000235:genetics; D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D055808:Drug Discovery; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000378:metabolism* / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000150:complications; D059467:Transcriptome
chemical_list: D015415:Biomarkers