Journal
PLOS ONE
Volume 7, Issue 7, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0040498
Keywords
-
Categories
Funding
- National Institutes of Health [GM79383, GM67168]
- National Science Foundation of China [30870474]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available