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Molecular Networks and the Human Interactome in Disease and Genetic Analysis

Molecular networks have become very useful tools in genetic studies, medical diagnoses, and protein synthesis. By taking a networks approach to medicine, scientists and engineers can analyze the links between various macromolecules in biological systems, which would enhance our understanding of how the relationships between genes and proteins influence disease progression and development. The network linking biological systems in the human body with their substituents and components is known as the human interactome.

Of particular interest is how the human interactome influences various physical conditions and processes. For example, gene interactions demonstrate how links in the human genome are important in embryonic lethality. According to Nature Medicine, out of the 25,000 genes identified in humans, it is estimated that 2,418 are associated with specific diseases. Not all of these genes are directly linked to the illness (they are not at the functional centre), but rather operate at the network periphery. The field of bioinformatics has used linkage mapping to model the connections between genes, and thus evaluate their influence on the disease. This method assumes that, if two genes are closely related within an allele and one gene is directly linked to a particular disease, it is very likely that the second gene is also linked to that disease. To explain from a networks point of view, let’s assume the genes are nodes A and B, and the disease is node C. A strong tie exists between nodes A and B, and there is also a strong tie between node A and node C. Thus, bioengineers assume that A is successful at strong triadic closure, and there is an additional edge that exists between node B and node C. This tie may be a weak one. Gene B could simply modify and influence other genes, such as gene A, which would then have an effect on disease C. It could also be a strong tie and directly affect the illness just as gene A does.

This trend can be seen in embryonic lethality. There are 1,665 genes that are in utero essential. If they were to malfunction or be absent, the embryo is very likely to die and not progress in its development. These genes are at the functional centre, where they have the strongest connection to embryonic lethality. However, there are numerous other genes that have an indirect effect on embryonic lethality. These genes operate in the periphery and will influence how the essential genes behave. They can serve as regulatory genes, which direct positive and negative feedback mechanisms within the process. They can also enhance or mitigate the effects of an essential gene, which can ultimately decide if the embryo lives or dies.

These networks also allow scientists to determine gene and protein function. Before linkage mapping was used, the purposes of lipoprotein lipase, beta-lactamase, and protein phosphate were unknown in the liver and adipose tissue. These genes were strongly linked to genes that play a significant role in obesity and diabetes. The unknown genes have a strong tie to the known genes, which have a strong tie to these diseases. This resulted in strong triadic closure, and the unknowns were connected to obesity and diabetes, which led to the discovery of their functions.


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October 2014