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The construction of common and specific significance subnetworks of Alzheimer's disease from multiple brain regions.

Kong W, Mou X, Zhang N, Zeng W, Li S, Yang Y - Biomed Res Int (2015)

Bottom Line: In this paper, commonly and specifically significant subnetworks were identified from six AD brain regions.The identified common subnetworks showed that inflammation of the brain nerves is one of the critical factors of AD and calcium imbalance may be a link among several causative factors in AD pathogenesis.In addition, the extracted specific subnetworks for each brain region revealed many biologically functional mechanisms to understand AD pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Information Engineering College, Shanghai Maritime University, Shanghai 201306, China.

ABSTRACT
Alzheimer's disease (AD) is a progressively and fatally neurodegenerative disorder and leads to irreversibly cognitive and memorial damage in different brain regions. The identification and analysis of the dysregulated pathways and subnetworks among affected brain regions will provide deep insights for the pathogenetic mechanism of AD. In this paper, commonly and specifically significant subnetworks were identified from six AD brain regions. Protein-protein interaction (PPI) data were integrated to add molecular biological information to construct the functional modules of six AD brain regions by Heinz algorithm. Then, the simulated annealing algorithm based on edge weight is applied to predicting and optimizing the maximal scoring networks for common and specific genes, respectively, which can remove the weak interactions and add the prediction of strong interactions to increase the accuracy of the networks. The identified common subnetworks showed that inflammation of the brain nerves is one of the critical factors of AD and calcium imbalance may be a link among several causative factors in AD pathogenesis. In addition, the extracted specific subnetworks for each brain region revealed many biologically functional mechanisms to understand AD pathogenesis.

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Related in: MedlinePlus

Functional subnetwork of the inflammatory response constructed by common genes.
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fig2: Functional subnetwork of the inflammatory response constructed by common genes.

Mentions: For the genes overlapped in overall the six brain regions, we selected a gene as a common gene when the number of interactions with other genes exceeds 90% quantile in different subnetworks. With this criterion, 206 common genes were extracted. It showed that most of the common genes play important roles in different brain regions. The molecular biological analysis revealed that many common genes were functionally related to metabolism, synaptic vesicle-mediated transport, transcriptional regulation, protein kinase phosphorylation, apoptosis, intracellular signaling, and cell cycle. Particularly, two functional subnetworks consisted of the common genes, which closely related to inflammation and calcium imbalance, were found distinctly dysregulated in all of the AD-affected brain regions. Figure 2 showed the inflammatory response subnetwork constructed by the related common genes. Diamonds in Figure 2 denoted the known risk genes of AD, circles presented our extracted common genes related to inflammation, and their different colors indicated different numbers of brain regions in which the gene was upregulated or downregulated. Table 1 provided the KEGG pathway analysis of genes in Figure 2.


The construction of common and specific significance subnetworks of Alzheimer's disease from multiple brain regions.

Kong W, Mou X, Zhang N, Zeng W, Li S, Yang Y - Biomed Res Int (2015)

Functional subnetwork of the inflammatory response constructed by common genes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383160&req=5

fig2: Functional subnetwork of the inflammatory response constructed by common genes.
Mentions: For the genes overlapped in overall the six brain regions, we selected a gene as a common gene when the number of interactions with other genes exceeds 90% quantile in different subnetworks. With this criterion, 206 common genes were extracted. It showed that most of the common genes play important roles in different brain regions. The molecular biological analysis revealed that many common genes were functionally related to metabolism, synaptic vesicle-mediated transport, transcriptional regulation, protein kinase phosphorylation, apoptosis, intracellular signaling, and cell cycle. Particularly, two functional subnetworks consisted of the common genes, which closely related to inflammation and calcium imbalance, were found distinctly dysregulated in all of the AD-affected brain regions. Figure 2 showed the inflammatory response subnetwork constructed by the related common genes. Diamonds in Figure 2 denoted the known risk genes of AD, circles presented our extracted common genes related to inflammation, and their different colors indicated different numbers of brain regions in which the gene was upregulated or downregulated. Table 1 provided the KEGG pathway analysis of genes in Figure 2.

Bottom Line: In this paper, commonly and specifically significant subnetworks were identified from six AD brain regions.The identified common subnetworks showed that inflammation of the brain nerves is one of the critical factors of AD and calcium imbalance may be a link among several causative factors in AD pathogenesis.In addition, the extracted specific subnetworks for each brain region revealed many biologically functional mechanisms to understand AD pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Information Engineering College, Shanghai Maritime University, Shanghai 201306, China.

ABSTRACT
Alzheimer's disease (AD) is a progressively and fatally neurodegenerative disorder and leads to irreversibly cognitive and memorial damage in different brain regions. The identification and analysis of the dysregulated pathways and subnetworks among affected brain regions will provide deep insights for the pathogenetic mechanism of AD. In this paper, commonly and specifically significant subnetworks were identified from six AD brain regions. Protein-protein interaction (PPI) data were integrated to add molecular biological information to construct the functional modules of six AD brain regions by Heinz algorithm. Then, the simulated annealing algorithm based on edge weight is applied to predicting and optimizing the maximal scoring networks for common and specific genes, respectively, which can remove the weak interactions and add the prediction of strong interactions to increase the accuracy of the networks. The identified common subnetworks showed that inflammation of the brain nerves is one of the critical factors of AD and calcium imbalance may be a link among several causative factors in AD pathogenesis. In addition, the extracted specific subnetworks for each brain region revealed many biologically functional mechanisms to understand AD pathogenesis.

Show MeSH
Related in: MedlinePlus