Chunk #48 — 4. ACHIEVING A SYSTEMS-BASED APPROACH TO STUDYING AD — 4.4 Interpreting Systems-based Analysis of AD: The Need for Alcohol-focused Ontologies
a collection of nodes, which would represent genes and/or proteins, and edges that represent the relationship between nodes and the means by which susceptibility to disease is transmitted through the system (Figure 2). Given the biology of AD, formal ontologies (i.e., formal models of a domain of knowledge and the relationship between entities that are being modeled) will be needed to interpret the findings of network models. An ever-evolving AD ontology could describe the cascade of events involved in the metabolic clearance of alcohol and the neuronal circuitry that regulates (1) alcohol’s rewarding and reinforcing effects (i.e., how alcohol activates the mesolimbic reward system (i.e., the nucleus accumbens neurons, ventral tegmental area, amygdala, and hippocampus), (2) executive control (i.e., the dorsolateral prefrontal cortex and its connections to the mesolimbic system), (3) the development of an alcohol habit (i.e., the cerebellum, the amygdala, the basal ganglia (primarily the striatum), and the hippocampus) (Zahr and Sullivan, 2008), and (4) behavioral response to stressors (i.e., the extra-hypothalamic corticotrophin releasing factor system; Merlo Pich et al., 1995). Formalizing an ontology of AD (including all of its different domains) will help to organize and communicate all of the important risk and protective factors and phenotypes
