How Gene Networks Can Uncover Novel CVD Players

Abstract

Cardiovascular diseases (CVD) are complex, involving numerous biological entities from genes and small molecules to organ function. Placing these entities in networks where the functional relationships among the constituents are drawn can aid in our understanding of disease onset, progression and prevention. While networks, or interactomes, are often classified by a general term, say lipids or inflammation, it is a more encompassing class of network that is more informative in showing connections among the active entities and allowing better hypotheses of novel CVD players to be formulated. A range of networks will be presented whereby the potential to bring new objects into the CVD milieu will be exemplified.

Keywords: cardiovascular disease; genetics; interactions; network; risk.

Fig 1

General aspects of gene networks. A) Networks are composed nodes and edges. Nodes can be genes, microRNAs, proteins, metabolites, food items, dietary patterns, diseases, or clinical measures of disease risk, among other entities. Edges are the connections between nodes. B) The relationship between two nodes, for example between two genes, can be altered according to the state or condition of a node. For example, different genetic variants (1*, 1**) have different and diverse effects on the nature of the interaction (edge) between node 1 and node 2, which are indicated by edges of different thicknesses or weights. C) Interactions within a network can be depicted in a response-specific manner. Here, several studies conducted in adipose after a high-fat meal have shown that node 3 is known to regulate expression of node 4, increasing its expression, while only one study shows that node 5 responds with increased expression. Thickness of the edge represents the amount of evidence while the coordinated increased expression of nodes 4 and 5 allow us to form an inferred relationship, albeit weak, between those two nodes. D) Known CVD genes (shaded) are networked via a common attribute to other non-CVD genes (unshaded). The more highly linked non-CVD genes become candidates in CVD research. E) Two CVD-relevant pathways are depicted where the shading of the node indicates strength of the relationship to CVD. A node (square) that bridges or links the two pathways becomes a CVD candidate.