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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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Specific subnetwork of MTG.
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fig7: Specific subnetwork of MTG.

Mentions: In MTG area, 24 specifically significant genes were extracted to achieve a maximal scoring subnetwork (Figure 7). The functions of MTG are associated with brain processes like recognizing familiar faces, ascertaining distance, and understanding meaning of words while reading. Our data exhibited that ANTXR1, BRCA1, CCND1, GATA2, KMT2D, NEDD9, PITPNM3, PLCG2, PRTFDC1, RB1CC1, SMAD1, and STAT5A were overexpressed. The ANTXR1 is a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. Aldose reductase contributes to diabetes-mediated mitochondrial dysfunction and damage through the activation of p53. The degree of mitochondrial dysfunction and damage determines whether hyperactivity (mild damage) or apoptosis (severe damage) will ensue [50]. BRCA1 is part of a complex that repairs double-strand breaks in DNA [51]; the overexpression of BRCA1 may suggest that DNA damage is serious; but BRCA1 mutation carriers are at an increased risk of prostate and breast cancer [52]. CCNDBP1 belongs to cyclin D family. The expression of cyclin D suggests that act to link growth factor signals with cell cycle transitions during G1 [53].


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)

Specific subnetwork of MTG.
© Copyright Policy
Related In: Results  -  Collection

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

fig7: Specific subnetwork of MTG.
Mentions: In MTG area, 24 specifically significant genes were extracted to achieve a maximal scoring subnetwork (Figure 7). The functions of MTG are associated with brain processes like recognizing familiar faces, ascertaining distance, and understanding meaning of words while reading. Our data exhibited that ANTXR1, BRCA1, CCND1, GATA2, KMT2D, NEDD9, PITPNM3, PLCG2, PRTFDC1, RB1CC1, SMAD1, and STAT5A were overexpressed. The ANTXR1 is a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. Aldose reductase contributes to diabetes-mediated mitochondrial dysfunction and damage through the activation of p53. The degree of mitochondrial dysfunction and damage determines whether hyperactivity (mild damage) or apoptosis (severe damage) will ensue [50]. BRCA1 is part of a complex that repairs double-strand breaks in DNA [51]; the overexpression of BRCA1 may suggest that DNA damage is serious; but BRCA1 mutation carriers are at an increased risk of prostate and breast cancer [52]. CCNDBP1 belongs to cyclin D family. The expression of cyclin D suggests that act to link growth factor signals with cell cycle transitions during G1 [53].

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