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Chunk #33 — DISCUSSION

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Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease.
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The construction of gene regulatory networks in a large sampling of human brain specimens has revealed many facets of the molecular interaction structure in LOAD, when compared to that in non-demented brains. A comprehensive characterization of gene network connectivity, its regulation and association to disease can provide critical insights into the underlying mechanisms, and identify genes that may serve as effective targets for therapeutic intervention. For instance, targeting genes that are the most central (highly connected) may be more effective in disrupting disease-related networks for the purpose of therapy, but that could be at the cost of more adverse effects. In summary, the utility of network-based approaches to complex disease includes: (1) elucidating the biological function and molecular context of a particular set of causal genes, (2) establishing a framework to map interaction between genes and network modules, (3) providing an objective filter for rank-ordering genes based on connectivity or other network features, (4) defining dynamic changes and corresponding causal regulators of the altered network structure associated with disease condition, (5) identifying modules and pathways causally related to disease, and